專(zhuān)利名稱(chēng):雙環(huán)氨基衍生物及含有此類(lèi)化合物的前列腺素d2拮抗劑的制作方法
技術(shù)領(lǐng)域:
本發(fā)明涉及雙環(huán)氨基衍生物和含有此類(lèi)化合物的前列腺素D2(以下簡(jiǎn)稱(chēng)PGD2)拮抗劑。
背景技術(shù):
本發(fā)明地雙環(huán)氨基衍生物中有一些已知可用作血栓素A2(TXA2)拮抗劑(日本專(zhuān)利公報(bào)(KOKOKU)No.79060/1993)。然而,日本專(zhuān)利公報(bào)(KOKOKU)No.79060/1993)只描述這些化合物可用作TXA2拮抗劑,而沒(méi)有提出其作為本發(fā)明所公開(kāi)的PGD2拮抗劑的有用性。
即,TXA2已知具有抗血小板凝集反應(yīng)、血栓形成等的作用這樣的活性。因此,TXA2拮抗劑已被認(rèn)為可用作抗血栓形成劑,而且也可用于通過(guò)拮抗TXA2來(lái)治療心肌梗塞或哮喘。
另一方面,本發(fā)明的PGD2拮抗劑可用于改善由于PGD2過(guò)量產(chǎn)生而引起的病癥。具體地說(shuō),它可作為一種藥物用于治療涉及肥大細(xì)胞機(jī)能障礙的疾病,例如,全身性肥大細(xì)胞沉積病和全身性肥大細(xì)胞活化失調(diào),而且也可用于治療氣管攣縮、哮喘、變應(yīng)性鼻炎、變應(yīng)性結(jié)膜炎、蕁麻疹、由于局部缺血性重復(fù)輸注而引起的傷害以及炎癥。
從以上所述顯而易見(jiàn),TXA2拮抗劑和PGD2拮抗劑就活性部位、作用機(jī)理和應(yīng)用而言是彼此完全不同的,有十分不同的特征。因此,從來(lái)就沒(méi)有人期待任何一種化合物能同時(shí)具有這些活性。
PGD2是借助于由免疫刺激或非免疫刺激活化的環(huán)氧酶的作用,從花生四烯酸通過(guò)PGG2和PGH2產(chǎn)生的,而且是肥大細(xì)胞產(chǎn)生和釋放的主要類(lèi)前列腺素化合物(Prostanoid)。PGD2有各種強(qiáng)效生理活性和病理活性。例如,PGD2會(huì)引起強(qiáng)烈氣管攣縮從而導(dǎo)致支氣管哮喘,而在全身性過(guò)敏狀態(tài)下它會(huì)使末梢血管擴(kuò)張從而導(dǎo)致過(guò)敏性休克。特別是,已經(jīng)有很多人注意到如下想法PGD2是過(guò)敏性鼻炎中對(duì)鼻塞發(fā)生負(fù)有責(zé)任的病因物質(zhì)之一。因此,已經(jīng)有人提出要開(kāi)發(fā)一種能對(duì)抗PGD2生物合成的抑制劑或PGD2受體拮抗劑,作為一種減輕鼻塞的藥物。然而,PGD2生物合成的抑制劑可能對(duì)其它生物體中前列腺素的合成產(chǎn)生很大影響,因此,理想的是開(kāi)發(fā)一種對(duì)PGD2受體專(zhuān)一的拮抗劑(阻滯劑)。
發(fā)明公開(kāi)
本發(fā)明者等人已經(jīng)進(jìn)行銳意研究以期開(kāi)發(fā)對(duì)PGD2受體專(zhuān)一的PGD2受體拮抗劑(阻滯劑),發(fā)現(xiàn)以下式(I)化合物或其鹽具有作為PGD2受體拮抗劑的強(qiáng)活性,而且是化學(xué)上和生物上穩(wěn)定的。
因此,本發(fā)明提供一種PGD2拮抗劑,該拮抗劑含有下面通式(I)所示的化合物或其鹽或其水合物作為一種活性成分
其中
是
或
A是亞烷基,任選地插入雜原子或亞苯基,含有氧代基,和/或有不飽和鍵;
B是氫、烷基、芳烷基或?;?;
R是COOR1,CH2OR2或CON(R3)R4;
R1是氫或烷基;
R2是氫或烷基;
R3和R4各自獨(dú)立地是氫、烷基、羥基或烷基磺酰基;
X1是單鍵、亞苯基、亞萘基、噻吩二基、吲哚二基,或噁唑二基;
X2是單鍵、-N=N-,-N=CH-,-CH=N-,-CH=N-N-,-CH=N-O-,-C=NNHCSNH-,-C=NNHCONH-,-CH=CH-,-CH(OH)-,-C(C1)=C(C1)-,-(CH2)n-,亞乙炔基,-N(R5)-,-N(R51)CO-,-N(R52)SO2-,-N(R53)CON(R54)-,-CON(R55)-,-SO2N(R56)-,-O-,-S-,-SO-,-SO2-,-CO-、噁二唑二基、噻二唑二基或四唑二基;
X3是烷基、鏈烯基、炔基、芳基、芳烷基、雜環(huán)基、環(huán)烷基、環(huán)烯基、亞噻唑啉基甲基(thiazolinylidenemethyl)、亞噻唑烷基甲基(thiazolidinylidenemethyl)、-CH=NR6或-N=C(R7)R8;
R5、R51、R52、R53、R54、R55和R56各是氫或烷基;
R6是氫、烷基、羥基、烷氧基、氨基甲酰氧基、硫代氨基甲酰氧基、脲基或硫代脲基;
R7和R8各自獨(dú)立地是烷基、烷氧基或芳基;
n是1或2;
Z是-SO2-或-CO-;以及
m是0或1;
其中環(huán)狀取代基可以有1-3個(gè)選自下述的取代基硝基、烷氧基、氨磺酰、取代或未取代的氨基、?;ⅤQ趸⒘u基、鹵素、烷基、炔基、羧基、烷氧羰基、芳烷氧羰基、芳氧羰基、甲磺酰氧基、氰基、鏈烯氧基、羥烷基、三氟甲基、烷硫基、-N=PPh3、氧代、硫代、肟基、烷氧亞氨基、苯基和亞烷二氧基。
實(shí)施本發(fā)明的最佳方案
可用作上述PGD2拮抗劑的化合物的具體例子包括式(I)的化合物或其鹽或其水合物,其中
是
m是0;且當(dāng)Z是SO2時(shí),X1和X2兩者都是單鍵;X3是烷基、苯基、萘基、Stylyl(苯乙烯基)、喹啉基或噻吩基;以及這些取代基中環(huán)狀取代基可任選地帶有選自下述的1-3個(gè)取代基硝基、烷氧基、取代或未取代的氨基、鹵素、烷基和羥烷基。
類(lèi)似地,具體例子包括式(I)的化合物或其鹽或其水合物,其中
是
當(dāng)m是1時(shí), X1和X2兩者都是單鍵;而X3是任選地被鹵素取代的苯基。
類(lèi)似地,具體例子包括式(I)的化合物或其鹽或其水合物,其中
是
當(dāng)m為1時(shí),X1是苯基,X2是-CH2-或-N=N-,而X3是苯基。
類(lèi)似地,式(I)化合物的例子包括式(1a)的化合物或其鹽或其水合物
其中A、B、R、X1、X2和X3的定義同上,其條件是其中(1)X1和X2是單鍵,而X3是取代或未取代的苯基,或萘基;以及(2)A是5-亞庚烯基,R是COOR1(R1是氫或甲基),X1是1,4-亞苯基,X2是單鍵,而X3是苯基的那些化合物除外。
類(lèi)似地,式(I)化合物的例子包括式(Ib)的化合物或其鹽或其水合物
其中
或
A、B、R、X1、X2和X3的定義同上,其條件是其中X1和X2是單鍵,而X3是苯基,以及其中X1是單鍵,X2是-O-,而X3是芐基的那些化合物除外。
更具體說(shuō),式(I)化合物的例子包括式(Ia)的那些化合物或其鹽或其水合物,其中X1和X2都是單鍵,X3是異噁唑基、噻二唑基、異噻唑基、嗎啉基、吲哚基、苯并呋喃基、二苯并呋喃基、二苯并二喔星基、苯并噻吩基、二苯并噻吩基、咔唑基、呫噸基、菲啶基、二苯并噁庚因基、二苯并硫雜七環(huán)基(thiepinyl)、肉啉基(cinnolyl)、苯并吡喃基(chromenyl)、苯并咪唑基或二氫苯并硫雜七環(huán)基(thiepinyl)。
類(lèi)似地,式(I)化合物的例子包括式(Ia)的那些化合物或其鹽或其水合物,其中X1是單鍵,X2是亞苯基,X3是鏈烯基、炔基、-CH=NR6或-N=C(R7)R8。
類(lèi)似地,式(I)化合物的例子包括式(Ia)的那些化合物或其鹽或其水合物,其中R是COOR1,X1是亞苯基或噻吩二基,X2是單鍵、-N=N-、-CH=CH-、-CONH-、-NHCO-或亞乙炔基,而X3是苯基、亞噻唑啉基甲基、亞噻唑烷基甲基或噻吩基。
更具體說(shuō),本發(fā)明的化合物(I)的例子包括其中
是
的式(Ib)化合物或其鹽或其水合物更優(yōu)選的化合物的例子包括其中R是COOR1(R1的定義同上)的式(Ib)化合物或其鹽或其水合物。
類(lèi)似地,化合物(I)的例子包括式(Ib)的那些化合物或其鹽或其水合物,其中X1是亞苯基或噻吩二基,X2是單鍵、-N=N-、-CH=CH-、亞乙炔基、-O-、-S-、-CO-、-CON(R55)-(R55的定義同上)、-N(R51)CO-(R51的定義同上),而X3是苯基。
更具體說(shuō),化合物(I)的例子包括式(Ib)的那些化合物或其鹽或其水合物,其中
是
更優(yōu)選的化合物的例子包括如下定義的那些化合物或其鹽或其水合物,其中B是氫,X1和X2兩者都是單鍵,X3是噻吩基、噻唑基、噻二唑基、異噻唑基、吡咯基、吡啶基、苯并呋喃基、苯并咪唑基、苯并噻吩基、二苯并呋喃基、二苯并噻吩基、喹啉基或吲哚基。類(lèi)似地,例子包括如下定義的那些化合物或其鹽或其水合物,其中X1是亞苯基、噻吩二基、吲哚二基或噁唑二基,X2是單鍵、-N=N-、-CH=CH-、
亞乙炔基、-S-或-O-,而X3是芳基或雜環(huán)基。
通式(Ia)和(Ib)的化合物是本發(fā)明的發(fā)明人合成的新化合物。
本說(shuō)明書(shū)中所用術(shù)語(yǔ)定義如下。
術(shù)語(yǔ)“亞烷基”是指C1-C9直鏈或支鏈亞烷基,例如亞甲基、甲基亞甲基、二甲基亞甲基、甲基乙基亞甲基、亞乙基、三亞甲基、四亞甲基、五亞甲基、六亞甲基、七亞甲基、1,8-亞辛基、1,9-亞壬基,或類(lèi)似的基團(tuán)。上述亞烷基中可以插入雜原子(氧、硫、氮等原子)或亞苯基(如1,4-亞苯基、1,3-亞苯基、1,2-亞苯基等),在其鏈的任何位置可含有一個(gè)氧代基,和/或有1個(gè)或多雙鍵或三鍵。其例子包括-(CH2)2-O-CH2-,-(CH2)2-O-(CH2)2-,-(CH2)2-O-(CH2)3-,-(CH2)2-O-(CH2)4-,-(CH2)2-O-(CH2)5-,-(CH2)2-O-(CH2)6-,-(CH2)2-S-(CH2)2-,-(CH2)3-S-(CH2)2-,-CH2-S-CH2-,-CH2-S-(CH2)4-,-CH2-N(CH3)-CH2,-CH2-NH-(CH2)2-,-(CH2)2-N(CH2CH3)-(CH2)3-,-(CH2)2-1,4-亞苯基-CH2-、-(CH2)2-O-1,3-亞苯基-CH2-、-(CH2)2-O-1,2-亞苯基-CH2-、-(CH2)2-O-1,4-亞苯基-CH2-、-CH=CH-S-CH2-1,4-亞苯基-CH2-、-CH=CH-S-1,3-亞苯基-(CH2)2-、2-氧代亞丙基、3-氧代亞戊基、5-氧代亞己基、亞乙烯基、1-亞丙烯基、2-亞丙烯基、1-亞丁烯基、2-亞丁烯基、3-亞丁烯基、1,2-亞丁二烯基、1,3-亞丁二烯基、1-亞戊烯基、2-亞戊烯基、3-亞戊烯基、4-亞戊烯基、1,2-亞戊二烯基、1,3-亞戊二烯基、1,4-亞戊二烯基、2,3-亞戊二烯基、2,4-亞戊二烯基、1-亞己烯基、2-亞己烯基、3-亞己烯基、4-亞己烯基、5-亞己烯基、1,2-亞己二烯基、1,3-亞己二烯基、1,4-亞己二烯基、1,5-亞己二烯基、2,3-亞己二烯基、2,4-亞己二烯基、2,5-亞己二烯基、3,4-亞己二烯基、3,5-亞己二烯基、4,5-亞己二烯基、1,1-二甲基-4-亞己烯基、1-亞庚烯基、2-亞庚烯基、3-亞庚烯基、4-亞庚烯基、5-亞庚烯基、2,2-二甲基-5-亞庚烯基、6-亞庚烯基、1,2-亞庚二烯基、1,3-亞庚二烯基、1,4-亞庚二烯基、1,5-亞庚二烯基、1,6-亞庚二烯基、2,3-亞庚二烯基、2,4-亞庚二烯基、2,5-亞庚二烯基、2,6-亞庚二烯基、3,4-亞庚二烯基、3,5-亞庚二烯基、3,6-亞庚二烯基、4,5-亞庚二烯基、4,6-亞庚二烯基或5,6-亞庚二烯基、1-亞丙炔基、3-亞丁炔基、2-亞戊炔基、5-亞己炔基、6-亞庚炔基、-(CH2)-CH=CH-O-(CH2)2-,-CH2-S-(CH2)3-,-CH2-順-CH=CH-1,2-亞苯基-CH2-, -CH=CH-1,4-亞苯基-(CH2)2-,-4-OXO-4,5-亞己烯基-,以及類(lèi)似的基團(tuán)。
術(shù)語(yǔ)“烷基”是指C1-C20直鏈或支鏈烷基,例如甲基、乙基、正丙基、異丙基、正丁基、異丁基、仲丁基、叔丁基、正戊基、異戊基、新戊基、叔戊基、己基、庚基、辛基、壬基、癸基、十一烷基、十二烷基、十三烷基、十四烷基、十五烷基、十六烷基、十七烷基、十八烷基、十九烷基、二十烷基等。
術(shù)語(yǔ)“芳基”是指C6-C14單環(huán)或稠環(huán),例如苯基、萘基(如1-萘基、2-萘基)、蒽基(如1-蒽基、2-蒽基、9-蒽基)、菲基(如2-菲基、3-菲基、9-菲基)、芴基(如2-芴基)等。苯基是特別優(yōu)選的。
術(shù)語(yǔ)“芳烷基”是指在上述烷基的任何可取代的位置上用上述芳基取代該烷基后所形成的基團(tuán)。其例子包括芐基、苯乙基、苯丙基(如3-苯基丙基)、萘甲基(如α-萘基甲基)、蒽甲基(如9-蒽基甲基)、菲甲基(如3-菲基甲基)等。
術(shù)語(yǔ)“?;笔侵笍闹弭人嵫苌鷣?lái)的C1-C9?;?,例如甲酰、乙酰、丙酰、丁酰、戊酰等。
術(shù)語(yǔ)“烷基磺?;笔侵赣蒙鲜鐾榛〈酋;笏纬傻幕鶊F(tuán),例如甲磺?;?、乙磺?;⒈酋;取?br>
術(shù)語(yǔ)“鏈烯基”是指C2-C20直鏈或支鏈的烯,相當(dāng)于含有1個(gè)或多個(gè)雙鍵的上述烷基。其例子包括乙烯基、1-丙烯基、2-丙烯基、1-丁烯基、2-丁烯基、3-丁烯基、1,2-丁二烯基、1-戊烯基、1,2-戊二烯基、2-己烯基、1,2-己二烯基、3-庚烯基、1,5-庚二烯基等。
術(shù)語(yǔ)“炔基”是指C2-C20直鏈或支鏈的炔基,相當(dāng)于含有1個(gè)或多個(gè)三鍵的上述烷基。其例子包括乙炔基、1-丙炔基、2-丙炔基、1-丁炔基、2-丁炔基、3-丁炔基等。
術(shù)語(yǔ)“雜環(huán)基”是指環(huán)上含有1個(gè)或多個(gè)獨(dú)立地選自氧、硫和/或氮原子的5-7元環(huán)狀基團(tuán),在任何可取代的位置上可任選地與碳環(huán)或其它雜環(huán)基稠合。其例子包括吡咯基(如1-吡咯基、3-吡咯基)、吲哚基(如2-吲哚基、3-吲哚基、6-吲哚基)、咔唑基(如2咔唑基、3-咔唑基)、咪唑基(如1-咪唑基、4-咪唑基)、吡唑基(如1-吡唑基、3-吡唑基)、苯并咪唑基(如2-苯并咪唑基、5-苯并咪唑基)、吲唑基(如3-吲唑基)、中氮茚基(如6-中氮茚基)、吡啶基(如2-吡啶基、3-吡啶基、4-吡啶基)、喹啉基(如8-喹啉基)、異喹啉基(如3-異喹啉基)、吖啶基(如1-吖啶基)、菲啶基(如2-菲啶基、3-菲啶基)、噠嗪基(2-噠嗪基)、肉啉基(如3-肉啉基)、2,3-二氮雜萘基(phthaladinyl)(如5-2,3-二氮雜萘基)、喹唑啉基(如2-喹唑啉基)、異噁唑基(如3-異噁唑基、4-異噁唑基)、苯并異噁唑基(如1,2-苯并異噁唑-4-基、2,1-苯并異噁唑-3-基)、噁唑基(如2-噁唑基、4-噁唑基、5-噁唑基)、苯并噁唑基(如2-苯并噁唑基)、苯并噁二唑基(如4-苯并噁二唑基)、異噻唑基(如3-異噻唑基、4-異噻唑基)、苯并異噻唑基(如1,2-苯并異噻唑-3-基、2,1-苯并異噻唑-5-基)、噻唑基(如2-噻唑基)、苯并噻唑基(如2-苯并噻唑基)、噻二唑基(如1,2,3-噻二唑-4-基)、噁二唑基(如1,3,4-噁二唑-2-基)、二氫噁二唑基(如4,5-二氫-1,2,4-噁二唑-3-基)、呋喃基(如2-呋喃基、3-呋喃基)、苯并呋喃基(如3-苯并呋喃基)、異苯并呋喃基(如1-異苯并呋喃基)、噻吩基(如2-噻吩基、3-噻吩基)、苯并噻吩基(1-苯并噻吩-2-基、2-苯并噻吩-1-基)、四唑基(如5-四唑基)、苯并間二氧雜環(huán)戊烯基(如1,3-苯并間二氧雜環(huán)戊烯-5-基)、二苯并呋喃基(如2-二苯并呋喃基、3-二苯并呋喃基)、二苯并噁庚因基(如二苯并[b,f]噁庚因-2-基)、苯并吡喃基(如2H-苯并吡喃-3-基、4H-苯并吡喃-2-基)、二苯并硫雜七環(huán)基(thiepinyl)(如二苯并[b,f]硫雜七環(huán)-3-基、二氫二苯并[b,f]硫雜七環(huán)-3-基)、嗎啉基(如1,4-嗎啉-4-基)、吩噻嗪基(phenothiadinyl)(2-吩噻嗪基)、環(huán)戊二烯并噻吩基(如環(huán)戊二烯并[b]噻吩-3-基)、環(huán)己二烯并噻吩(cyclohexathienyl)(如環(huán)己二烯并[b]噻吩-3-基)等。
術(shù)語(yǔ)“環(huán)烷基”是指C3-C8環(huán)烷基,例如環(huán)丙基、環(huán)丁基、環(huán)戊基、環(huán)己基等。
術(shù)語(yǔ)“環(huán)烯基”是指C3-C8環(huán)烯基,例如環(huán)丙烯基(如1-環(huán)丙烯基)、環(huán)丁烯基(如2-環(huán)丁烯-1-基)、環(huán)戊烯基(1-環(huán)戊烯-1-基)、環(huán)己烯基(1-環(huán)己烯-1-基)等。
術(shù)語(yǔ)“烷氧基”是指C1-C6烷氧基,例如甲氧基、乙氧基、正丙氧基、異丙氧基、正丁氧基等。
在“取代或未取代的氨基”的定義中,取代的氨基的例子包括一取代或二取代氨基,如甲基氨基、乙基氨基、二甲基氨基、環(huán)己基氨基、苯基氨基、二苯基氨基、或環(huán)狀氨基,如哌啶子基、哌嗪子基(piperadino)或嗎啉代基。
術(shù)語(yǔ)“酰氧基”是指從上述“酰基”衍生的酰氧基,例如乙酰氧基、丙酰氧基、丁酰氧基、戊酰氧基等。
術(shù)語(yǔ)“鹵素”是指氟、氯、溴和碘。
術(shù)語(yǔ)“烷氧羰基”是指從上述“烷氧基”衍生的烷氧羰基基團(tuán),例如甲氧羰基、乙氧羰基、苯氧羰基等。
術(shù)語(yǔ)“芳烷氧羰基”是指從上述“芳烷基”衍生的芳烷氧羰基基團(tuán),例如芐氧羰基、苯乙氧羰基等。
術(shù)語(yǔ)“芳氧羰基”是指從上述“芳基”衍生的芳氧羰基基團(tuán),例如苯氧羰基、萘氧羰基等。
術(shù)語(yǔ)“鏈烯氧基”是指從上述“鏈烯基”衍生的鏈烯氧基基團(tuán),例如乙烯氧基、1-丙烯氧基、2-丁烯氧基等。
術(shù)語(yǔ)“羥烷基”是指從上述“烷基”衍生的羥烷基基團(tuán),例如羥甲基、羥乙基、羥丙基等。
術(shù)語(yǔ)“烷硫基”是指從上述“烷基”衍生的烷硫基基團(tuán),例如甲硫基、乙硫基、丙硫基等。
術(shù)語(yǔ)“亞烷二氧基”是指從C1-C3亞烷二氧基,例如亞甲二氧基、亞乙二氧基、亞丙二氧基等。
在“亞苯基”、“亞萘基”、“噻吩二基”、“吲哚二基”、“噁唑二基”、“噁二唑二基”和“四唑二基”的情況下,所述基團(tuán)可以結(jié)合到任何兩個(gè)可取代部位上的相鄰基團(tuán)上。
在上述定義中,當(dāng)取代基為環(huán)狀基團(tuán)時(shí),該取代基可被1-3個(gè)選自下述的取代基取代硝基、烷氧基、氨磺酰、取代或未取代的氨基、?;ⅤQ趸?、羥基、鹵素、烷基、炔基、羧基、烷氧羰基、芳烷氧羰基、芳氧羰基、甲磺酰氧基、氰基、鏈烯氧基、羥烷基、三氟甲基、烷硫基、-N=PPh3、氧代、硫代、肟基、烷氧亞氨基、苯基和亞烷二氧基。這些取代基可以結(jié)合到環(huán)上任何可取代的位置上。
化合物(I)的鹽的例子包括與堿金屬(如鋰、鈉或鉀)、堿土金屬(如鈣)、有機(jī)堿(如tromethamine、三甲胺、三乙胺、2-氨基丁烷、叔丁胺、二異丙基乙胺、正丁基甲胺、環(huán)己胺、二環(huán)己胺、N-異丙基環(huán)己胺、糠胺、芐胺、甲芐胺、二芐胺、N,N-二甲基芐胺、2-氯芐胺、4-甲氧基芐胺、1-亞萘基甲胺、二苯基芐胺、三苯胺、1-萘胺、1-氨基蒽(anthoracene)、2-氨基蒽、脫氨樅胺、N-甲基嗎啉或吡啶)、氨基酸(如賴(lài)氨酸、或精氨酸)等形成的鹽。
術(shù)語(yǔ)“水合物”是指式(I)化合物或其鹽的水合物。其例子包括一水合物和二水合物。
本發(fā)明化合物由通式(I)表示,并包括任何類(lèi)型的立體異構(gòu)體(如非對(duì)映體、差向異構(gòu)體、對(duì)映體)的外消旋化合物形式。
在通式(I)化合物中,其中m=1的那些化合物,尤其下面表3b和3c所列的那些化合物是日本專(zhuān)利公開(kāi)No 180862/1990中所述的已知化合物。
在通式(I)化合物中,其中m=0的那些化合物〔即通式(I′)所示的那些化合物〕可通過(guò)使通式(II)的氨基化合物與相當(dāng)于部分結(jié)構(gòu)Z-X1-X2-X3的磺酸或羧酸的活性衍生物反應(yīng)來(lái)制備,如下所示
其中A、B、R、X1、X2、X3、Y和Z的定義同上。
相當(dāng)于部分結(jié)構(gòu)Z-X1-X2-X3的磺酸是通式X3-X2-X1-SO2H所示的化合物,而相當(dāng)于所述部分結(jié)構(gòu)的羧酸是通式X3-X2-X1-COOH所示的化合物。這類(lèi)磺酸或羧酸的活性衍生物是指相應(yīng)的鹵化物(如氯化物、溴化物、碘化物)、酸酐(如與甲酸或乙酸形成的混合酸酐)、活性酯(如琥珀酰亞胺酯),其例子通常包括用于氨基基團(tuán)?;孽;瘎?。在用于胺和羧酸之間的縮合反應(yīng)的縮合劑(如二環(huán)己基碳化二亞胺(DCC)、1-乙基-3-(3-二甲基氨基丙基)碳化二亞胺、N,N′-碳酰二咪唑)的存在下,羧酸X3-X2-X1-COOH不轉(zhuǎn)化成活性衍生物就可用在該反應(yīng)中。
該反應(yīng)可在通常用于氨基基團(tuán)?;臈l件下進(jìn)行。例如,在使用酰鹵進(jìn)行縮合的情況下,該反應(yīng)要在溶劑,例如醚類(lèi)溶劑(如二乙醚、四氫呋喃、二噁烷)、苯類(lèi)溶劑(如苯、甲苯、二甲苯)、鹵代烴類(lèi)溶劑(如二氯甲烷、二氯乙烷、氯仿)、乙酸乙酯、二甲基甲酰胺、二甲基亞砜、乙腈或類(lèi)似的溶劑存在下進(jìn)行,如有必要,可在堿(例如,有機(jī)堿如三乙胺、吡啶、N,N-二甲基氨基吡啶、N-甲基嗎啉;無(wú)機(jī)堿如氫氧化鈉、氫氧化鉀、碳酸鉀,或類(lèi)似的堿)存在下進(jìn)行,反應(yīng)可在冷卻下、在室溫或加熱的條件下進(jìn)行,優(yōu)選在-20℃至冷卻的溫度下,或從室溫至反應(yīng)體系的回流溫度下進(jìn)行,反應(yīng)時(shí)間為幾分鐘至若干小時(shí),優(yōu)選0.5-24小時(shí),更優(yōu)選為1-12小時(shí)。
其它活性衍生物或游離酸和胺(II)之間的反應(yīng)的反應(yīng)條件可按一般方法根據(jù)各個(gè)活性衍生物或游離酸的特性來(lái)決定。
反應(yīng)產(chǎn)物可用傳統(tǒng)的純化方法,例如溶劑萃取、色譜、重結(jié)晶,或類(lèi)似的方法進(jìn)行提純。
作為本發(fā)明方法的原料化合物(II)的具體例子列舉如下。3-氨基[2.2.1]二環(huán)化合物的例子包括7-(3-氨基二環(huán)[2.2.1]庚-2-基)-5-庚烯酸、7-(3-氨基二環(huán)[2.2.1]庚-2-基)-2,2-二甲基-5-庚烯酸、7-(N-甲基-3-氨基二環(huán)[2.2.1]庚-2-基)-5-庚烯酸、6-(3-氨基二環(huán)[2.2.1]庚-2-基)-5-己烯酸。2-氨基-6,6-二甲基[3.1.1]二環(huán)化合物的具體例子包括7-(2-氨基-6,6-二甲基二環(huán)[3.1.1]庚-3-基)-5-庚烯酸。在這些起始化合物中,庚烯酸鏈可以是飽和的,形成庚酸鏈,可以插入雜原子或雜基團(tuán)如-O-、-S-、-NH-,或亞苯基,或被氧代基取代。這類(lèi)化合物的例子包括7-(3-氨基二環(huán)[2.2.1]庚-2-基)庚酸、4-〔2-(2-氨基二環(huán)[3.1.1]庚-3-基)乙氧基苯基乙酸、7-(3-氨基二環(huán)[2.2.1]庚-2-基)-6-氧代-庚酸。這些起始化合物或者在日本專(zhuān)利公告No.79060/1993或23170/1991中有記載,或者可按其中所述方法制備。
相當(dāng)于部分結(jié)構(gòu)Z-X1-X2-X3的磺酸X3-X2-X1-SO2H和羧酸X3-X2-X1-COOH是指帶有對(duì)應(yīng)于上述Xs的取代基的磺酸或羧酸。就是說(shuō),其例子包括鏈烷-磺酸或鏈烷-羧酸,鏈烯-磺酸或-羧酸,鏈炔-磺酸或-羧酸,環(huán)烷-磺酸或-羧酸,芳基-磺酸或-羧酸,芳烷基-磺酸或-羧酸,雜環(huán)取代-磺酸或-羧酸,雜芳基烷基-磺酸或-羧酸,以及取代的氨基-磺酸或-羧酸?;撬岷汪人岣髯远伎梢杂猩鲜鋈〈?。這些磺酸和羧酸可從市場(chǎng)上購(gòu)得,或可容易地從已知化合物按已知方法合成。如有必要,反應(yīng)后可將磺酸和羧酸轉(zhuǎn)化成相應(yīng)的上述活性衍生物。例如,當(dāng)需要酰鹵時(shí),可按已知方法,例如文獻(xiàn)(如Shin-Jikken-Kagaku-Koza,第14卷,1787頁(yè)(1978);Synthesis(合成),852-854頁(yè)(1986);Shin-Jikken-Kagaku-Koza,第22卷,115頁(yè)(1992))中所述的方法讓該化合物與亞硫酰鹵(如亞硫酰氯)、鹵化磷(如三氯化磷、五氯化磷)或草酰鹵(如草酰氯)反應(yīng)。其它活性衍生物也可按已知方法制備。
在目的化合物(I)中,其中側(cè)鏈A含有不飽和鍵,尤其雙鍵的那些化合物也可通過(guò)使下面通式(III)的醛衍生物與相當(dāng)于該側(cè)鏈A-R的其余部分的內(nèi)鎓鹽化合物在用于Wittig反應(yīng)的條件下進(jìn)行反應(yīng)來(lái)制備。
其中A、B、R、X1、X2、X3、Y和Z的定義同上。
起始化合物(III)可按照例如日本專(zhuān)利公開(kāi)No.256650/1990中所述方法制備。此外,相當(dāng)于側(cè)鏈A-R的其余部分的內(nèi)鎓鹽化合物可按已知方法讓三苯膦與相應(yīng)的鹵代鏈烷酸或其酯衍生物、醚衍生物或酰胺衍生物在堿存在下進(jìn)行反應(yīng)來(lái)合成。
在目的化合物(I)中,其中R為COOH的那些化合物,如果希望的話,可轉(zhuǎn)化成相應(yīng)的酯衍生物、醇衍生物、醚衍生物、酰胺衍生物。例如,酯衍生物可按傳統(tǒng)方法通過(guò)使羧酸酯化來(lái)制備。酯衍生物還原時(shí)就得到醇衍生物,而當(dāng)進(jìn)行酰胺化時(shí)就得到酰胺衍生物。醚衍生物可通過(guò)醇衍生物的O-烷基化制得。
本發(fā)明的化合物(I)顯示通過(guò)與PGD2受體結(jié)合產(chǎn)生的離體抗PGD2的拮抗效果,而且可作為一種藥物用于治療那些涉及因PGD2過(guò)量產(chǎn)生而引起的肥大細(xì)胞機(jī)能障礙的疾病。例如,化合物(I)可作為一種藥物用于治療多種疾病,例如全身性肥大細(xì)胞沉積病和全身性肥大細(xì)胞活化失調(diào),也可用于治療氣管攣縮、哮喘、變應(yīng)性鼻炎、變應(yīng)性結(jié)膜炎、蕁麻疹、因局部缺血性重復(fù)輸注而引起的損傷和發(fā)炎?;衔?I)顯示出對(duì)活體鼻塞的預(yù)防效果,因此,尤其可作為一種藥物用于治療它們。
當(dāng)使用本發(fā)明的化合物(I)進(jìn)行治療時(shí),可以把它配制成經(jīng)口給藥和非經(jīng)腸給藥用的常用配方。含有本發(fā)明化合物(I)的醫(yī)藥組合物可以呈經(jīng)口和非經(jīng)腸給藥用劑型。具體地說(shuō),可以把它配制成經(jīng)口給藥用配方,例如片劑、膠囊劑、顆粒劑、散劑、糖漿劑等;非經(jīng)腸給藥用配方,例如經(jīng)靜脈內(nèi)、經(jīng)肌內(nèi)或經(jīng)皮下注射用的可注射溶液或懸浮液,吸入劑,眼滴劑,鼻滴劑,栓劑,或經(jīng)皮配方如軟膏劑。
在制備這些配方時(shí),可以使用本門(mén)技術(shù)上一般熟練人員已知的載體、賦形劑、溶劑和基劑。在片劑的情況下,它們是通過(guò)使有效成分(活性組分)連同輔助成分一起壓縮或配制來(lái)制備的??捎幂o助成分的實(shí)例包括藥物上可接受的賦形劑,例如粘結(jié)劑(如玉米淀粉)、填料(如乳糖、微晶纖維素)、崩解劑(如淀粉甘醇酸鈉)或潤(rùn)滑劑(如硬脂酸鎂)。片劑可以進(jìn)行適當(dāng)包衣。在液體配方如糖漿劑、溶液劑或懸浮劑的情況下,它們可以含有懸浮劑(如甲基纖維素),乳化劑(如卵磷脂)、防腐劑等。在可注射配方的情況下,它可以呈溶液或懸浮液或者油基或水基乳液的形式,這些劑型可以含有懸浮穩(wěn)定劑或分散劑等。在吸入劑的情況下,把它配制成一種適用于吸入器的液體配方。在眼滴劑的情況下,把它配制成一種溶液劑或一種懸浮液劑。特別是,在用于治療鼻塞的鼻藥的情況下,可以把它作為一種用常規(guī)配制方法制備的溶液或懸浮液或作為一種用粉末化劑(如羥丙基纖維素、carbopole)配制的粉末劑使用,對(duì)鼻腔給藥。此外,它也可以在與一種低沸點(diǎn)溶劑一起灌裝到一種專(zhuān)用容器中之后作為一種氣霧劑使用。
盡管化合物(I)的適用劑量因給藥途徑、患者的年齡、體重、性別或病情以及一起使用的藥物種類(lèi)(如果有的話)而異,而且最終應(yīng)當(dāng)由醫(yī)生確定,但在經(jīng)口給藥的情況下,日劑量一般可以是每kg體重約0.01~100mg、較好約0.01~10mg、更好的是約0.1~10mg。在非經(jīng)腸給藥的情況下,日劑量一般可以是每kg體重約0.001~100mg、較好約0.001~1mg、更好的是約0.01~1mg。這種日劑量可以分成1~4次給藥。
以下實(shí)例是為了進(jìn)一步說(shuō)明本發(fā)明而提供的,不要理解為對(duì)其范圍的限定。實(shí)例1
(Z)-7-〔(1S,2R,3R,4R)-3-氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸甲酯(II-1)(251mg,1.0mmol)溶于二氯甲烷(8ml)中,然后在氮?dú)夥諊孪蚱渲屑尤肴野?0.238ml,2.00mmol)。在冰冷卻下往該混合物中加入2-氯磺?;讲⑦秽?350mg,1.31mmol),然后將該混合物攪拌30分鐘,并讓其溫?zé)嶂潦覝?。反?yīng)混合物經(jīng)硅膠柱色譜提純(正己烷/乙酸乙酯(1∶4))及正己烷(10ml)重結(jié)晶后得到(Z)-7-〔(1S,2R,3R,4R)-3-(2-二苯并呋喃基)磺酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸甲酯(1a-1)(342mg,0.710mmol)。產(chǎn)率71%,熔點(diǎn)115-116℃。元素分析(C27H31NO5S)
計(jì)算值(%)C,67.34;H,6.49;N,2.91;S,6.66
實(shí)測(cè)值(%)C,67.16;H,6.47;N,2.99;S,6.66 IR(CHCl3)3382,3024,2952,2874,1726,1583,1465,1442,1319,1245,1154,1121,1104,1071,1019,890,840,817/cm.1H NMR(CDCl3)δ0.94-1.92(14H,m),2.15-2.24(3H,m),2.99-3.07(1H,m),3.66(3H,s),4.98(1H,d,J=6.6Hz),5.10-5.22(2H,m),7.39-7.46(1H,m),7.51-7.70(3H,m),7.87-8.13(2H,m),8.5 3(1H,d,J=2.1Hz)[α]D=-0.6°(CHCl3,c=1.01%,23℃).([α]365=+37.0°(CHCl3,c=1.01%,23℃).
(Z)-7-〔(1S,2R,3R,4R)-3-(2-二苯并呋喃基)磺酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸甲酯(1a-1)(234mg,0.50mmol)溶解在甲醇(6ml)/四氫呋喃(4ml)中。在冰冷卻下往該溶液中加入1N氫氧化鉀(1.50ml,1.50mmol)。待反應(yīng)混合物溫?zé)嶂潦覝睾螅屍浞磻?yīng)16小時(shí),然后濃縮脫除溶劑。往殘留物中加入乙酸乙酯(50ml)和水(10ml),然后再加入1NHCl(2.00ml,2.00mmol),并分離出有機(jī)層。該有機(jī)層用飽和鹽水洗滌,用無(wú)水硫酸鈉干燥,然后濃縮。殘留物經(jīng)硅膠柱色譜提純(含0.2%乙酸的正己烷/乙酸乙酯(1∶1))后得到(Z)-7-〔(1S,2R,3R,4R)-3-(2-二苯并呋喃基)磺酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸(1a-2)(203mg,0.434mmo1)。產(chǎn)率87%,油狀物。IR(CHCl3)3266,3026,2952,2874,1708,1465,1443,1423,1319,1267,1245,1153,1121,1104,1072,906/cm.1H NMR(CDCl3)δ0.93-1.94(14H,m),2.12-2.19(1H,m),2.26(2H,t,J=7.2Hz),3.00-3.08(1H,m),5.12-5.25(2H,m),5.26(1H,d,J=6.6Hz),7.3 8-7.45(1H,m),7.51-7.70(3H,m),7.87-8.13(2H,m),8.54(1H,d,J=2.1Hz).[α]D=+6.8°(CHCl3,c=1.08%,23℃).
(Z)-7-〔(1S,2R,3R,4R)-3-(2-二苯并呋喃基)磺酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸(1 a-2)(453mg,0.97mmol)溶解在甲醇(5ml)中。加入1N甲醇鈉/甲醇(1.034N,0.937ml,0.97mmol)后讓混合物溫?zé)嶂潦覝?,進(jìn)行反應(yīng)1小時(shí)。用蒸餾法脫除溶劑后得到該酸的鈉鹽(1a-3)(457mg,0.933mmol)。產(chǎn)率96%。無(wú)定形粉末。元素分析(C26H28NO5SNa 0.6H20)
計(jì)算值C,62.41;H,5.88;N,2.80;S,6.41;Na,4.59
實(shí)測(cè)值C,62.45;H,5.92;N,2.99;S,6.49;Na,4.46IR(KBr)434,3280,3074,3007,2952,2873,1566,1467,1444,1417,1344,1315,1270,1248,1200,1189,1154,1124,1107,1075,1058,895,842,818/cm.1H NMR(CD3OD)δ1.02-2.05(16H,m),2.1 6-2.23(1H,m),2.94-3.00(1H,m),4.98-5.05(2H,m),7.41-7.48(1H,m),7.53-7.62(1H,m),7.66(1H,d,J=8.4Hz),7.77(1H,d,J=8.4Hz),8.57(1H,d,J=2.1Hz).[α]D=-15.2°(CH3OH,c=1.07%,22℃).
實(shí)例2
將按照日本專(zhuān)利公告No.79060/1993參考例4所述方法制得的(Z)-7-〔(1S,2R,3R,4R)-3-氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸甲酯三氟乙酸鹽(II-2)(232mg,0.636mmol)溶解在二氯甲烷(5ml)中。在冰冷卻下往該溶液中加入三乙胺(0.279ml,2.00mmol)和4-聯(lián)苯基碳酰氯,然后在同一溫度下攪拌7小時(shí)。反應(yīng)混合物經(jīng)硅膠柱色譜提純(乙酸乙酯/正己烷(1∶4))后得到(Z)-7-〔(1S,2R,3R,4R)-3-(4-聯(lián)苯基)碳酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸甲酯(1K-11)(221mg,0.512mmol)。將該化合物(1K-11)(190mg,0.440mmol)溶解在甲醇(6ml)中。在冰冷卻下往該溶液中加入1N KOH(1.10ml,1.10mmol),然后在室溫下攪拌15小時(shí)。將反應(yīng)混合物真空濃縮。往殘留物中加入水(20ml)和1N HCl(2ml),然后用乙酸乙酯萃取。有機(jī)層用飽和鹽水洗滌,用無(wú)水硫酸鈉干燥,然后濃縮。殘留物經(jīng)硅膠柱色譜提純(含0.3%乙酸的乙酸乙酯/己烷(1∶1))后得到(Z)-7-〔(1S,2R,3R,4R)-3-(4-聯(lián)苯基)碳酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸(1K-12)(172mg,0.412mmol)。產(chǎn)率94%。
按照下面的方式也可制備如下化合物。實(shí)例3
在室溫下在氮?dú)夥諊峦射寤?-羧基丁基三苯基磷鎓(14.8g,33.3mmol)和四氫呋喃(80ml)組成的懸浮液中加入叔丁酸鉀(7.55g,67.3mmol)。在室溫下攪拌1小時(shí)后混合物冷卻到-20℃,慢慢加入N-〔(1S,2S,3S,4R)-3-甲酰甲基二環(huán)[2.2.1]庚-2-基〕苯磺酰胺(III-1)(日本專(zhuān)利公開(kāi)No.256650/1990,參考例2)(3.25g,11.1mmol)的四氫呋喃(20ml)溶液。在-20℃攪拌約1小時(shí)后,撤除冰浴,混合物再攪拌1小時(shí)。往該反應(yīng)溶液中加入2N HCl,混合物用乙酸乙酯萃取,用水和鹽水洗滌,濃縮。往所得粗產(chǎn)物中添加甲苯和1N氫氧化鈉,然后分離出水層。有機(jī)層用水洗滌,洗滌液與前面得到的水層合并。加入2N HCl后,該水溶液用乙酸乙酯萃取。萃取物用水和鹽水洗滌,用硫酸鈉干燥,濃縮。殘留物用硅膠柱色譜提純,得到(Z)-7-〔(1R,2S,3S,4S)-3-苯磺酰氨基二環(huán)[2.2.1]庚-2-基〕-5-庚烯酸鈣(1d-1)(3.29g,產(chǎn)率79%,熔點(diǎn)62℃)。元素分析(C20H27N04S)
計(jì)算值C,63.63;H,7.21;N,3.71;S,8.49
實(shí)測(cè)值C,63.56;H,7.21;N,3.83;S,8.43[α]D=+5.3±0.5°(CHCl3,C=1.003%,22℃)[α]D=+27.1±0.7°(MeOH,c=1.015%,24℃)IR(液體石蠟)3282,3260,3300,2400,1708,1268,1248,1202,1162,1153,1095,1076/cm.1H NMRδ0.88-2.10(m,14H),2.14(brS,1H),2.34(t,J=7.2Hz,2H),2.95-3.07(m,1H),5.13-5.35(m,3H),7.45-7.64(m,3H),7.85-7.94(m,2H),9.52(brS,1H)。
按照上述實(shí)例所述方法制備的化合物列于下面各表中。表1a
No.R1 X1-X2-X3
1a-22 H
1a-23 H
No. R1 X1-X2-X3
1a-34 CH3
1a-41 H
No.R1X1-X2-X3
No. R1 X1-X2-X3
1a-84 H
1a-85 H
1a-86 H
1a-87 H
No.R1 X1-X2-X3
1a-94 H
1a-95 H
1a-96 H
1a-97 H
No R1 X1-X2-X3
1a-102 CH3
No. R1 X1-X2-X3
1a-124 CH3
1a-129 CH3
1a-134 H
No. R1X1-X2-X3
No. R1X1-X2-X31a-152 H
1a-155 H
1a-156 H
1a-157 H
1a-158 H
1a-159 H
1a-160 H
No. R1 X1-X2-X31a-161 H
1a-162 H
1a-163 H
1a-164 H
1a-165 H
1a-166 H
1a-167 H
1a-168 H
1a-169 H
1a-170 H
No. R1 X1-X2-X31a-173 H
1a-174 H
1a-181 H
No. R1X1-X2-X31a-184 H
1a-185 H
No.X1-X2-X31a-194
1a-195
1a-198
1a-199
1a-200
1a-0201
1a-202
1a-203
No.X1-X2-X31a-204
1a-205
1a-206
1a-207
1a-208
1a-209
1a-210
1a-211
1a-212
1a-213
No. X1-X2-X31a-214
1a-215
1a-216
1a-217
1a-218
1a-219
1a-220
1a-221
1a-222
1a-223
No. X1-X2-X31a-224
1a-225
1a-226
1a-227
1a-228
1a-229
1a-230
1a-231
1a-232
1a-233
1a-234
1a-235
No. X1-X2-X31a-236
1a-237
1a-238
1a-239
1a-240
1a-241
1a-242
1a-243
1a-244
1a-245
1a-246
No. X1-X2-X31a-247
1a-248
1a-249
1a-250
1a-251
1a-252
1a-253
1a-254
1a-255
1a-256
1a-257
No. X1-X2-X31a-258
1a-259
1a-260
1a-261
1a-262
1a-263
1a-264
1a-265
1a-266
1a-267
1a-268
1a-269
1a-270
1a-271
No. X1-X2-X31a-272
1a-273
1a-274
1a-277
1a-280
1a-281
1a-282
1a-283
No. X1-X2-X3
1a-293
1a-294
No. X1-X2-X3
表1b
No. R1 X1-X2-X31b-1 CH3
1b-2 CH3
1b-3 H
1b-6 H
1b-7 H
1b-8 H
1b-9 H
1b-10H
No. R1 X1-X2-X31b-11H
1b-12H N
1b-13H
1b-14H
1b-15H
表1c
No. R1 X1-X2-X31c-1 CH3
1c-2 CH3
1c-3 K
1c-4 H
1c-5 H
1c-6 H
1c-7 H
1c-8 H
1c-9 H
1c-10 H
表1d
No. R3 R4 X1-X2-X31d-1 H SO2CH3
1d-5 H SO2CH3
1d-6 H SO2CH3
1d-7 H SO2CH3
1d-8 H SO2CH3
1d-9 H SO2CH3
1d-10 H SO2CH3
No. R3 R4 X1-X2-X31d-11HSO2CH3
1d-12HSO2CH3
1d-13HSO2CH3
1d-14HSO2CH3
1d-15HSO2CH3
表1e
No.R1X1-X2-X3
1e-3 H
1e-4 H
1e-5 H
1e-6 H
1e-7 H
1e-8 H
1e-9 H
1e-10 H
表1f
No.R2 X1-X2-X31f-1 H
1f-2 H
1f-3 H
1f-4 H
1f-5 H
1f-6 H
1f-7 H
1f-8 H
1f-9 H
1f-10 H
表1g
No. R1 X1-X2-X31g-1H
1g-2H
1g-3H
1g-4H
1g-5H
1g-6H
1g-7H
1g-8H
1g-9H
1g-10 H
1g-11 H
表1h
No. R1 X1-X2-X31h-1H
1h-2H
1h-3H
1b-4H
1h-5H
1h-6H
1h-7H
1h-8H
1h-9H
1h-10 H
表Ii
No. R2X1-X2-X31i-1H
1i-2H
1i-3H
1i-6H
1i-7H
1i-12 H
表1j
No. R1 X1-X2-X3
1j-8CH3
No. R1 X1-X2-X31j-17H
1j-22H
1j-27H
No R1X1-X2-X31j-30H
1j-31H
1j-32H
1j-33H
1j-34H
1j-35H
1j-36H
1j-37H
1j-38H
表1k
No.R1 X1-X2-X31k-1 H
1k-4 H
1k-5 H
1k-6 H
1k-7 H
1k-8 H
1k-9 H
1k-10 H
1k-11 CH3
1k-12 H
No. R1 X1-X2-X31k-13H
11-14H
1k-15H
1k-16H
1k-17H
1k-18H
11-19H
1k-20H
表1m
No. R1X1-X2-X3
No. R1X1-X2-X3
1m-21H
1m-22H
1m-31H
1m-32H
1m-33H
No. R1 X1-X2-X31m-34H
1m-35H
1m-36H
1m-37H
1m-38H
1m-39H
1m-40H
表2a
No. R1 X1-X2-X3
No. R1 X1-X2-X3
2a-31CH3
No. R1 X1-X2-X3
No. R1 X1-X2-X3
No.R1 X1-X2-X3
No.R1X1-X2-X3
2a-119 H
2a-120 H
2a-121 H
2a-122 H
2a-123 H
2a-124 H
2a-125 H
No. R1 X1-X2-X32a-126H
2a-127H
2a-128H
2a-129H
2a-130H
2a-131H
2a-132H
2a-133H
2a-134H
2a-135H
2a-136H
No. R1 X1-X2-X32a-137H
2a-138H
2a-139H
2a-140H
2a-141H
2a-142H
2a-143H
2a-144H
2a-145H
2a-146H
2a-147H
No. R1 X1-X2-X32a-148H
2a-149H
2a-150H
2a-151H
2a-152H
2a-153H
2a-154H
2a-155H
2a-156H
2a-157H
2a-158H
2a-159H
No. R1 X1-X2-X32a-160H
2a-161H
2a-162H
2a-163H
2a-164H
2a-165H
2a-166H
2a-167H
2a-168H
2a-169H
2a-170H
No. R1X1-X2-X32a-171H
2a-172H
2a-173H
2a-174H
2a-175H
2a-176H
2a-177H
2a-178H
2a-179H
2a-180H
2a-181H
2a-182H
No. R1 X1-X2-X32a-183H
2a-184H
2a-185H
2a-186H
2a-187H
2a-188H
2a-189H
2a-190H
2a-191H
2a-192H
2a-193H
No. R1 X1-X2-X32a-194H
2a-195H
2a-196H
2a-197H
2a-200H
2a-201H
2a-202H
2a-203H
No. X1-X2-X32a-204
2a-205
2a-206
2a-207
2a-208
2a-209
2a-210
2a-211
2a-212
2a-213
No. X1-X2-X32a-214
2a-215
2a-216
2a-217
2a-218
2a-219
2a-220
2a-221
2a-222
2a-223
No. X1-X2-X32a-224
2a-225
2a-226
2a-227
2a-228
2a-229
2a-230
2a-231
2a-232
2a-233
No.X1-X2-X32a-234
2a-235
2a-236
2a-237
2a-238
2a-239
2a-240
2a-241
2a-242
2a-243
No. X1-X2-X32a-244
2a-245
2a-246
2a-247
2a-248
2a-249
2a-250
2a-251
No. X1-X2-X32a-252
2a-253
2a-254
2a-255
2a-256
2a-257
No. X1-X2-X32a-258
2a-259
2a-260
2a-261
2a-262
2a-263
2a-264
2a-265
2a-266
2a-267
No. X1-X2-X32a-268
2a-269
2a-270
2a-271
2a-272
2a-273
2a-274
2a-275
2a-276
2a-277
No. X1-X2-X32a-278
2a-279
2a-280
2a-281
2a-282
2a-283
2a-284
2a-285
2a-286
2a-287
No. X1-X2-X32a-288
2a-289
2a-290
2a-291
2a-292
2a-293
2a-294
2a-295
2a-296
No. X1-X2-X32a-297
2a-298
2a-299
2a-300
2a-301
2a-302
2a-303
2a-304
2a-305
2a-306
No. X1-X2-X32a-307
2a-308
2a-309
2a-310
2a-311
2a-312
2a-313
2a-314
2a-315
表2b
No. R1X1-X2-X32b-1H
2b-2H
表2C
No. R1X1-X2-X32c-1H
2c-2H
2c-3H
表2d
No. R1X1-X2-X32d-1H
2d-2H
2d-3H
表2e
No. R1 X1-X2-X32e-1H
2e-2H
2e-3H
表2f
No. R1 X1-X2-X32f.1H
2f-2H
2f-3H
表2g
No. R3 R4 X1-X2-X32g-1H SO2CH3
表2h
No. X1-X2-X32h-1
2b-2
2h-3
2h-4
2h-5
2b-6
表2i
No. X1-X2-X3
2i-3
2i-4
2i-5
2i-6
表2j
No. X1-X2-X3
2j-4
2j-5
2j-6
表2k
No. X1-X2-X3
2k-3
2k-4
2k-5
2k-6
表3a
No.R1 X1-X2-X3
3a-8 H
3a-9 H
3a-14 CH3
No. R1 X1-X2-X3
3a-25 H-(CH2)3CH33a-26CH33a-27 H-(CH2)7CH33a-28CH3
3a-29H
3a-30CH3
表3b
No.R1 X1-X2-X3
3b-3 H
3b-4 H
表3c
No.R1X 1-X2-X33c-1 H
表3d
No. R1 X1-X2-X3
3d-3 Na
3d-4 Na
No. R1X1-X2-X33d-16 H
3d-17 H
3d-18 H-(CH3)3CH33d-19 CH33d-20 H-NHCH6
3d-23 H
3d-24 H
外消旋化合物
外消旋化合物
外消旋化合物表3e
No. R1 X1-X2-X33e-11/2Ca
下面列出上述化合物的物理化學(xué)性質(zhì)。下面的化合物編號(hào)對(duì)應(yīng)于上面表中所列的化合物編號(hào)。No.1a-4[α]D=-11.5°(CHCl3,C=1.01,23.5℃)。No.1a-5[α]D=-10.0°(CHCl3,C=1.01,25.0℃)。No.1a-6 CDCl3300MHz 0.93-1.96(14H,m),2.20-2.26(3H,m),3.03(1H,m),3.67(3H,s),4.99(1H,d,J=6.6H z),5.10-5.24(2H,m),7.37-7.51(3H,m),7.54-7.64(3H,m),7.76-7.88(2H,m),8.11(1 H,m).IR(CHCl3)3384,3278,3026,2952,2874,1727,1436,1411,1324,1155,1097/cm.[α]D=-9.0°(CHCl3,C=1.04,22.0℃).No.1a-7 CDCl3300MHz 0.93-2.00(14H,m),2.18(1H,m),2.28(2H,t,J=7.2Hz),3.04(1H,m),5.15-5.25(2H,m),5.28(1H,d,J=6.9Hz),7.36-7.50(3H,m),7.54-7.63(3H,m),7.76-7.89(2H,m),8.12(1H,m).IR(CHCl3)3268,3028,2952,2872,1708,1452,1410,1324,1155,1097/cm.[α]D=-9.1°(CHCl3,C=1.01,24.0℃).No.1a-8CDCl3300MHz 0.94-1.99(14H,m),2.21-2.29(3H,m),3.05(1H,m),3.67(3H,s),4.92(1H,d,J=6.3Hz),5.14-5.30(2H,m),7.70-7.78(6H,m),7.96-8.01(2H,m).IR(CHCl3)3376,3272,3018,2946,2868,1727,1616,1435,1388,1324,1162,1130,1069/cm.[α]D=+1.6°(CHCl3,C=l.01,24.0℃)、mp.117-119℃.No.1a-9CDCl3 300MHz0.95-2.08(14H,m),2.19(1H,m),2.32(2H,t,J=7.2Hz),3.06(1H,m),5.20-5.30(2H,m),5.34(1H,d,J=6.6Hz),7.69-7.78(6H,m),7.96-8.03(2H,m).IR(CHCl3)3260,3020,2950,2868,1708,1389,1324,1162,1130,1069/cm.[α]D=+13.3°(CHCl3,C=1.05,24.0℃).mp. 118-120℃No.1a-10CDCl3 300MHz0.96-1.98(14H,m),2.15-2.32(3H,m),3.04(1H,m),3.66(3H,s),5.12-5.26(5H,m), 7.67-7.78(4H,m),7.93-8.07(4H,m).IR(CHCl3)3276,3018,2946,2868,1726,1595,1435,1341,1162,1095/cm.[α]D=-1.5 °(CHCl3,C=1.01,25.0℃).mp.133-139℃.No.1a-11CD3OD 300MHz1.05-1.98(14H,m),2.13-2.22(3H,m),2.97(1H,m),5.09-5.22(2H,m),7.85-7.92(4H,m),7.95-8.05(4H,m).IR(KBr)3385,3261,3069,3003,2954,2872,1708,1596,1428,1413,1378,1343,1326,1236,1186,1160,1096/cm.mp.144-146℃.No.1a-12CDCl3 300MHz0.96-1.96(14H,m),2.22-2.27(3H,m),3.03(1H,m),3.66(3H,s),3.87(3H,s),4.86(1H,d,J=6.9Hz),5.18-5.24(2H,m),6.99-7.02(2H,m),7.55-7.66(2H,m),7.66-7.69(2H,m),7.89-7.92(2H,m).IR(CHCl3)3374,3270,3016,2948,2870,1726,1608,1518,1487,1458,1437,1248,1157,1037.[α]D=+4.2°(CHCl3,C=1.01,24℃).mp.85-87℃.No.1a-13CDCl3 300MHz0.97-1.99(14H,m),2.18(1H,m),2.30(2H,t,J=7.2Hz), 3.04(1 H,m),3.86(3H,s),5.18(1H,d,J=5.7Hz),5.23-5.26(2H,m),6.99-7.02(2H,m),7.55-7.58(2H,m),7.66-7.68(2H,m),7.89-7.92(2H,m).IR(CHCl3)3380,3260,3020,2948,2868,1708,1608,1519,1487,1458,1306,1293,1248,1156/cm.[α]D=+18.3°(CHCl3,C=1.00,25.5℃).No.1a-14CDCl3 300MHz0.98-2.00(14H,m),2.20(1H,m),2.25(2H,t,J=7.2Hz),3.02(1H,m),3.67(3H,s),4.85(1H,d,J=6.3Hz),5.19-5.25(2H,m),7.13(1H,dd,J=4.8,3.6Hz),7.39(1H,d,J=4.8Hz),7.40(1H,d,J=3.6Hz),7.71-7.74(2H,m),7.86-7.89(2H,m).IR(CHCl3)3374,3270,3018,2946,2868,1727,1593,1434,1322/cm.[α]D= +5.6°(CHCl3,C=1.01,24℃).mp.69-71℃.No.1a-15CDCl3 300MHz0.95-2.00(14H,m),2.17(1H,m),2.32(2H,t,J=7.2Hz),3.03(1H,m),5.20(1H,d,J=6.9Hz),5.24 -5.28(2H,m),7.13(1H,dd,J=4.8,3.3Hz),7.38(1H,d,J=4.8Hz),7.43(1H,d,J=3.3Hz),7.73(2H,d,J=8.4Hz),7.87(2H,d,J=8.4Hz).IR(CHCl3)3260,3022,2948,2868,1709,1593,1404,1321,1154/cm.[α]D=+20.8°(CHCl3,C=1.07,23℃).mp.71-73℃.No.1a-16CDCl3 300MHz0.98-2.00(14H,m),2.27(2H,t,J=7.5Hz),2.28(1H,m),3.13(1H,m),3.66(3H,s),4.90(1H,d,J=6.9Hz),5.25-5.29(2H,m),7.40-7.65(6H,m),7.76(1H,d,J=8.4Hz),7.90-8.02(4H,m).IR(CHCl3)3376,3276,3018,2946,2868,1726,1593,1435,1394,1322,1159/cm.[α]D= +7.0°(CHCl3,C=1.07,24℃).No.1a-17CDCl3 300MHz1.02-2.07(14H,m),2.25(1H,m),2.34(2H,t,J=6.6Hz),3.14(1H,m),5.28-5.33(3H,m),7.39-7.57(4H,m),7.62-7.65(2H,m),7.76(1H,d,J=8.1Hz),7.89-8.02(4H,m).IR(CHCl3)3260,2948,2868,1709,1593,1394,1324,1157/cm.[α]D=+20.2 °(CHCl3,C=1.02,24℃).No.1a-18CDCl3 300MHz1.05-1.97(14H,m),2.25(2H,t,J=7.2Hz),2.33(1H,m),3.12(1H,m),3.67(3H,s),4.91(1H,d,J=6.6Hz),5.24-5.29(2H,m),7.24(1H,d,J=3.9Hz),7.39-7.45(3H,m),7.56(1H,d,J=3.9Hz),7.59-7.62(2H,m).IR(CHCl3)3372,3272,3018,2946,2868,1727,1433,1331,1152/cm.[α]D=-5.7°(CHCl3,C=1.01,23℃).No.1a-19CDCl3 300MHz1.05-2.05(14H,m),2.28-2.33(3H,m),3.13(1H,m),5.18(1H,d,J=6.3Hz),5.27-5.31(2H,m),7.24(1H,d,J=4.2Hz),7.39-7.42(3H,m),7.56(1H,d,J=4.2Hz),7.58- 7.62(2H,m).IR(CHCl3)3372,3254,3018,2948,2868,1707,1431,1328,1151/cm.[α]D=+4.5°(CHCl3,C=1.01,21.5℃).No.1a-20CDCl3 300MHz1.05-2.00(14H,m),2.26(2H,t,J=7.5Hz),2.33(1H,m),3.11(1H,m),3.68(3H,s),4.92(1H,d,J=6.0Hz),5.27(2H,m),7.05(1H,m),7.10(1H,d,J=3.6Hz),7.25(1H,m),7.32(1H,m),7.49(1H,d,J=3.6Hz).IR(CHCl3)3372,3272,3018,2946,2686,1727,1438,1417,1333,1151/cm.[α]D=-9.2°(CHCl3,C=1.01,25℃).No.1a-21CDCl3 300MHz1.02-2.01(14H,m),2.28-2.34(3H,m),3.13(1H,m),5.12(1H,d,J=6.9Hz),5.28-5.32(2H,m),7.06(1H,m),7.10(1H,d,J=3.9Hz),7.25(1H,m),7.32(1H,m),7.50(1H,d,J=3.9Hz).IR(CHCl3)3350,3250,2948,1709,1440,1420,1330,1151.[α]D=+2.5°(CHCl3,C=1.00,25℃).No.1a-22CDCl3 300MHz0.96-2.05(14H,m),2.25(1H,m),2.35(2H,t,J=7.0Hz),3.11(1H,m);5.20-5.34(2H,m),5.41(1H,d,J=6.6Hz),7.31-7.49(5H,m),7.62(1H,d,J=7.8Hz),8.11(1H,d.d,J=1.8and7.8Hz),8.35(1H,d,J=1.8Hz).IR(CHCl3)3384, 3271,3025,2958,1708,1608,1559,1537,1357,1168/cm.[α]D=+18.3°(CHCl3,C=0.31,22℃).No.1a-23CDCl3 300MHz0.97-2.07(14H,m),2.24(1H,m),2.35(2H,t,J=6.9Hz),3.09(1H,m),3.86(3H,s),5.24-5.35(2H,m),5.44(1H,d,J=6.3Hz),6.97-7.00(2H,m),7.26-7.28(2H,m),7.59(1H,d,J=8.1Hz),8.06(1H,d.d,J=2.1and8.1Hz),8.29(1H,d,J=2.1Hz).IR(CHCl3)3384,3270,2959,1709,1609,1535,1519,1357,1302,1255,1226,1169/cm.[α]D=+17.0 °(CHCl3,C=1.00,21℃).No.1No. 1a-24CDCl3 300MHz0.95-2.00(14H,m),2.20-2.25(1H,m),2.26(2H,t,J=7.2Hz),3.02-3.10(1H,m),3.66(3H,s),4.92(1H,d,J=6.6Hz),5.16-5.31(2H,m),7.52-7.60(3H,m),7.94-8.06(6H,m).IR(CHCl3)3376,3020,2946,2868,1726,1436,1366,1298,1164,1090,890/cm.[α]D=+11.2±0.5°(CHCl3,C=1.04,23.5℃)mp.101-103℃No.1a-25CDCl3 300MHz0.95-2.08(14H,m),2.15-2.22(1H,m),2.33(2H,t,J=6.9Hz),3.02-3.10(1H,m),5.21-5.31(2H,m),5.34(1H,d,J=6.3Hz),7.51-7.59(3H,m),7.92-8.07(6H,m).IR(CHCl3)3258,3022,2948,2868,1707,1399,1328,1298,1163,1089,1051,892/cm.[α]D=+29.8±0.7°(CHCl3,C=1.05,25℃)mp.158-160℃No.1a-26Anal.Calcd for C26H30N3O4SNa0.8H2OC,60.29;H,6.15;N,8.11;S,6.19;Na,4.44;FoundC,60.15;H,6.19;N,8.15;S,6.03;Na,4.98.[α]D=-16.6°(CHCl3,C=1.04,25.0℃).No.1a-27CDCl3 300MHz0.92-1.98(14H,m),2.20(1H,m),2.26(2H,t,J=7.5Hz),3.03(1H,m),3.12(6H,s),3.66(3H,s),4.87(1H,d,J=6.6Hz),5.16-5.32(2H,m),6.73-6.80(2H,m),7.88-8.00(6H,m).IR(CHCl3)3376,3020,2946,1726,1601,1518,1442,1419,1362,1312,1163,1133,1088/cm.[α]D=+55.3°(CHCl3,C=0.53,24.0℃).mp.158-168℃No.1a-28CDCl3+CD3OD 300MHz0.99-2.14(14H,m),2.21(1H,m),2.31(2H,t,J=7.2Hz),2.94(1H,m),3.12(6H,s),5.22-5.38(2H,m),6.73-6.81(2H,m),7.87-8.00(6H,m).IR(KBr)3434,3309,2946,1708,1604,1520,1442,1416,1366,1312,1252,1164,1155,1134,1091/cm.[α]D=不可測(cè)定(有顏色,能量不足)mp.193-196℃No.1a-29CD3OD 300MHz1.02-1.96(14H,m),2.10(2H,t,J=7.8Hz),2.16(1H,m),2.98(1H,m),3.11(6H,s),5.07-5.27(2H,m),6.80-6.87(2H,m),7.84-8.00(6H,m).IR(KBr)3433,308 7,3004,2949,2871,1604,1565,1520,1444,1420,1364,1312,1253,11638,1136,1090/cm.[α]D=不可測(cè)定No.1a-30CDCl3 300MHz0.95-1.99(14H,m),2.22(1H,m),2.26(2H,t,J=7.2Hz),2.35(3H,s),3.06(1H,m),3.66(3H,s),4.95(1H,d,J=6.9Hz),5.15-5.30(2H,m),7.26-7.32(2H,m),7.97-8.06(6H,m).IR(CHCl3)3374,2996,2946,2868,1763,1728,1591,1495,1435,1368,1299,1228,1192,1163,1139/cm.[α]D=+12.9°(CHCl3,C=1.04,26.0℃).No.1a-31CDCl3 300MHz0.93-2.01(14H,m),2.19(1H,m),2.31(2H,t,J=7.2Hz),2.35(3H,s),3.06(1H,m),5.17-5.32(2H,m),7.25-7.32(2H,m),7.96-8.07(6H,m).IR(CHCl3)3267,3028,2952,2874,1759,1708,1592,1495,1368,1328,1299,1163,1138,1088,1050,1008/cm.[α]D=+21.7°(CHCl3,C=0.51,22℃).No.1a-32CDCl3 300MHz0.93-1.99(14H,m),2.21(1H,m),2.27(2H,t,J=7.2Hz),3.05(1H,m),3.67(3H,s),4.92(1H,d,J=6.6Hz),5.15-5.30(2H,m),6.72(1 H,s),6.96-7.00(2H,m),7.86-8.04(6H,m).IR(CHCl3)3374,3276,3018,2946,2686,1725,1605,1589,1502,1433,1396,1330,1271,1164,1135,1089/cm. [α]D=+18.6°(CHCl3,c=1.00,26.0℃).No.1a-33CDCl3+CD3OD 300MHz0.98-2.08(14H,m),2.20(1H,m),2.28(2H,t,J=7.2Hz),2.98(1H,m),5.18-5.32(2H,m),6.92-6.99(2H,m), 7.85-8.02(6H,m).IR(KBr)3385,3248,2948,2876,1717,1601,1505,1430,1399,1296,1280,1219,1165,1136,1092/cm.[α]D=-16.0°(CH3OH,C=1.08,26.0℃).mp.208-210℃No.1a-34mp.82-83℃[α]D=+10.6°(CHCl3,C=1.01,23.5℃).No.1a-35mp.80-82℃[α]D=-1.8°(CHCl3,C=1.07,22.0℃).No.1a-36TLC Rf=0.25(ethyl acetate/n-hexane=1∶1(0.3%乙酸))No.1a-37CDCl3 300MHz0.92-1.96(14H,m),2.21(1H,m),2.27(2H,t,J=7.4Hz),3.01(1H,m),3.66(3H,s),4.71(1H,d,J=6.6Hz),5.14-5.29(2H,m),7.12(1H,d,J=16.2Hz),7.24(1H,d,J=16.2Hz),7.28-7.42(3H,m),7.52-7.56(2H,m),7.62(2H,d,J=8. 7Hz),7.85(2H,d,J=8.7Hz).IR(CHCl3)3384,3283,3023,2954,2876,1730,1595,1494,1317,1163,1147/cm.[α]D=+10.5°(CHCl3,C=1.01,24℃).mp 116-117℃.No.1a-38CDCl3 300MHz0.92-1.99(14H,m),2.17(1H,m),2.32(2H,t,J=7.2Hz),3.02(1H,m),5.23-5.29(3H,m),7.11(1H,d,J=16.2Hz),7.23(1H,d,J=16.2Hz),7.28-7.41(3H,m),7.52-7.55(2H,m),7.61(2H,d,J=8.7Hz),7.86 (2H,d,J=8.7Hz).IR(CHCl3)3515,3384,3270,3022,3015,2957,2876,2669,1708,1595,1496,1320,1157/cm.[α]D=+27.1°(CHCl3,C=1.02,24℃).No.1a-39CDCl3 300MHz0.92-1.99(14H,m),2.15(1H,m),2.28(2H,t,J=7.4Hz),3.0 1(1H,m),3.68(3H,s),4.96(1H,d,J=6.6Hz),5.16-5.32(2H,m),6.60(1H,d,J=12.0Hz),6.74(1H,d,J=12.0Hz),7.16-7.23(5H,m),7.35(2H,d,J=8.4Hz),7.72(2H,d,J=8.4Hz).IR(CHCl3)3384,3283,3023,3015,2954,2876,1730,1595,1493,1324,1163,1147/cm.[α]D=+13.7°(CHCl3,C=1.00,24℃).No.1a-40CDCl3 300MHz0.90-2.16(14H,m),2.12(1H,m),2.34 (2H,t,J=7.2Hz),3.02(1H,m),5.16(1H,d,J=6.9Hz),5.23-5.34(2H,m),6.60(1H,d,J=12.3Hz),6.74(1H,d,J=12.3Hz),7.14-7.24(5H,m),7.35(2H,d,J=8.1Hz),7.72(2H,d,J=8.1Hz).IR(CHCl3)3515,3384,3269,3025,3021,3014,2957,2876,2668,1709,1595,1322,1162,1147/cm.[α]D=+26.4°(CHCl3,C=1.00,24℃).No.1a-41CDCl3 300MHz0.98-1.99(14H,m),2.17(1H,m),2.32(2H,t,J=7.2Hz),3.00(1H,m),3.84(3H,s),5.20-5.26(3H,m),6.90-6.95(2H,m),6.98(1H,d,J=16.2Hz),7.17(1H,d,J=16.2Hz),7.46-7.49(2H,m),7.58(2H,d,J=8.4Hz),7.83(2H,d,J=8.4Hz).IR(CHCl3)3258,3018,3002,2950,1709,1590,1509,1457,1404,1302,1250,1153/cm.[α]D=+30.2°(CHCl3,C=1.00,23℃).mp.99-100℃No.1a-42CDCl3 300MHz1.01-1.99(14H,m),2.28(2H,t,J=7.2Hz),2.30(1H,m),3.10(1H,m),3.66(3H,s),5.07(1H,br),5.25-5.30(2H,m),6.98-7.04(2H,m),7.16(1H,d,J=16.2Hz),7.28-7.37(3H,m),7.47-7.50(3H,m).IR(CHCl3)3372,3276,3020,2946,2870,1727,1491,1433,1331,1152/cm.[α]D=-11.5°(CHCl3,C=1.07,21.5℃).No.1a-43CDCl3 300MHz0.98-2.00(14H,m),2.11-2.36(3H,m),3.12(1H,m),5.10(1H,d,J=6.6Hz),5.29-5.32(2H,m),6.99-7.04(2H,m),7.23(1H,d,J=21.6Hz),7.32-7.49(6H,m).IR(CHCl3)3380,3248,3020,2948,2868,1709,1491,1430,1329,1151/cm.[α]D=+3.4°(CHCl3,C=1.03,25℃).No.1a-44CDCl3 300MHz1.00-2.00(14H,m),2.13(1H,m),2.29(2H,t,J=7.4Hz),2.90-3.13(5H,m),3.68(3H,s),4.74(1H,d,J=6.6Hz),5.15-5.30(2H,m),7.18-7.29(7H,m),7.76(2H,d,J=8.1Hz).IR(CHCl3)3384,3282,3063,3028,3023,3016,2953,2876,1730,1599,1496,1319,1157/cm.[α]D=+2.3°(CHCl3,C=1.00,25℃).mp.85.0-86.0℃No.1a-45CDCl3 300MHz0.90-2.05(14H,m),2.09(1H,m),2.35(2H,t,J=6.9Hz),2.90-3.13(5H,m),5.18(1H,d,J=6.6Hz),5.24-5.34(2H,m),7.10-7.27(7H,m),7.76(2H,d,J=8.4Hz).IR(CHCl3)3510,3384,3270,3087,3063,3026,3018,3014,2955,2876,2670,1708,1599,1496,1318,1157/cm.[α]D=+8.5°(CHCl3,C=1.01,25℃).No.1a-46[α]D=+6.8°(CHCl3,C=1.05,25℃),mp.99-100℃.No.1a-47CDCl3 300MHz0.97-2.01(14H,m),2.14(1H,m),2.36(2H,t,J=7.2Hz),3.02(1H,m),5.23(1H,d,J=5.4Hz),5.26-5.30(2H,m),7.37-7.39(3H,m),7.54-7.58(2H,m),7.63-7.66(2H,m),7.85-7.88(2H,m).IR(CHCl3)3375,3260,3022,2948,2212,1707,1596,1497,1396,1322,1160/cm.[α]D=+25.0°(CHCl3,C=1.02,24℃). mp.117-118℃.No.1a-48CD3OD 30MHz1.05-1.93(14H,m),2.10-2.15(3H,m),2.96(1H,m),5.08-5.28(2H,m),7.38-7.40(3H,m),7.554-7.56(2H,m),7.69(1H,d,J=8.4Hz),7.87(1H,d,J=8.4Hz).No.1a-49CDCl3 300MHz0.96-1.97(14H,m),2.24(1H,m),2.31(2H,t,J=6.9Hz),3.05(1H,m),3.69(3H,s),5.15(1H,d,J=6.6Hz),5.25-5.27(2H,m),7.40-7.43(3H,m),7.61-7.64(2H,m),7.85(1H,d,J=8.1Hz),8.07(1H,dd,J=8.1,1.8Hz),8.58(1H,d,J=1.8Hz).IR(CHCl3)3374,3020,2948,2870,2212,1726,1606,1530,1493,1437,1345,11671cm.[α]D=+2.4°(CHCl3,C=1.03,25℃). mp.77-79℃.No.1a-50CDCl3 300MHz1.00-2.02(14H,m),2.20(1H,m),2.34(2H,t,J=6.6Hz),3.08(1H,m),5.26-5.29(2H,m),5.41(1H,d,J=6.9Hz),7.40-7.43(3H,m),7.61-7.64(2H,m),7.84(1H,d,J=8.1Hz),8.07(1H,dd,J=8.4,1.8Hz),8.57(1H,dd,J=1.8Hz).IR(CHCl3)3380,3254,2952,2880,2212,1707,1606,1531,1493,1409,1344,1166.[α]D=+23.4°(CHCl3,C=1.00,25℃).No.1a-51CDCl3 300MHz0.95-1.98(14H,m),2.23(1H,m),2.30(2H,t,J=7.2Hz),3.00(1H,m),3.66(3H,s),4.56(2H,br),4.70(1H,d,J=6.9Hz),5.20-5.29(2H,m),7.15(1H,dd,J=7.8,1.8Hz),7.23(1H,d,J=1.8Hz),7.36-7.39(3H,m),7.46(1H,d,J=7.8Hz),7.53-7.56(2H,m).IR(CHCl3)3494,3386,3028,2952,2874,1725,1611,1559,1497,1422,1317,1162/cm.No.1a-52CDCl3 300MHz0.96-2.04(16H,m),2.20(1H,m),2.36(2H,t,J=6.9Hz),2.99(1H,m),5.17(1H,d,J=6.3Hz),5.28-5.31(2H,m),7.18(1H,dd,J=9.6,1.8Hz),7.25(1H,m),7.36- 7.39(3H,m),7.46(1H,d,J=7.8Hz),7.52-7.56(2H,m).IR(CHCl3)3482,3378,3260,3022,2948,2868,1708,1612,1495,1422,1317/cm.[α]D=+15.0°(CHCl3,C=1.00,24℃).No.1a-53CDCl3 300MHz1.01-2.05(15H,m),2.31(2H,t,J=7.2Hz),3.10(1H,m),3.67(3H,s),5.02(1H,br),5.26-5.33(2H,m),7.18(1H,d,J=4.2Hz),7.36-7.39(3H,m),7.48(1H,d,J=4.2Hz),7.51-7.55(2H,m). IR(CHCl3)3372,3270,3018,3004,2946,2868,2202,1726,1486,1433,1336,1154/cm.[α]D=+0.6°(CHCl3,C=1.11,25℃),[α]436+17.8°(CHCl3,C=1.11,25℃).No.1a-54CDCl3 300MHz0.99-2.11(14H,m),2.27(1H,m),2.37(2H,t,J=7.5Hz),3.13(1H,m),5.16(1H,d,J=6.6Hz),5.31-5.35(2H,m),7.18(1H,d,J=3.6Hz),7.37-7.39(3H,m),7.50(1H,d,J=3.6Hz),7.52-7.55(2H,m).IR(CHCl3)3484,3370,3246,2948,2868,2202,1708,1486,1429,1335,1153/cm.[α]D=+17.8°(CHCl3,C=1.00,24℃). mp.95-96℃No.1a-55CDCl3 300MHz0.95-1.92(14H,m),2.15(1H,m),2.24(2H,t,J=7.5Hz),3.00(1H,m),3.66(3H,s),5.10-5.30(3H,m),7.40-7.60(7H,m),7.70(1H,d,J=7.8Hz),8.08(1H,d,J=8.1Hz). IR(CHCl3)3356,3020,2948,2868,2210,1727,1490,1458,1437,1341,1165/cm.[α]D=-58.4°(CHCl3,C=1.00,26℃). mp.84-85℃.No.1a-56CDCl3 300MHz0.95-1.95(14H,m),2.10(1H,m),2.27(2H,t,J=6.9Hz),3.00(1H,m),5.17-5.21(2H,m),5.38(1H,d,J=6.9Hz),7.39-7.60(7H,m),7.70(1H,dd,J=7.8,1.5Hz),8.07(1H,J=6.6,1.5Hz).IR(CHCl3)3364,3026,2952,2874,2212,1707,1597,1491,1458,1411,1341,1164/cm.[α]D=-43.1°(CHCl3,C=1.00,25℃).No.1a-57CDCl3 300MHz0.99-1.97(14H,m),2.23-2.30(3H,m),3.01 (1H,m),3.67(3H,s),5.17-5.26(3H,m),7.36-7.38(3H,m),7.50- 7.56(3H,m),7.60(1H,m),7.83(1H,m),8.05(1H,m).IR(CHCl3)3376,3020,2946,2870,1727,1598,1491,1437,1412,1330,1245,1163/cm.[α]D=-12.7°(CHCl3,C=1.00,24℃).No.1a-58CDCl3 300MHz0.97-1.98(14H,m),2.20(1H,m),2.33(2H,t,J=6.9Hz),3.02(1H,m),5.19-5.28(3H,m),7.36-7.38(3H,m),7.47-7.55(3H,m),7.69(1H,m),7.83(1H,m),8.04(1H,m).IR(CHCl3)3376,3260,3022,3002,2948,2868,2220,1708,1598,1490,1455,1412,1327,1162/cm.[α]D=-8.6°(CHCl3,C=1.01,24℃).No.1a-59CDCl3 300MHz0.95-1.99(24H,m),2.20(1H,m),2.28(2H,t,J=7.8Hz),2.53(1H,s),2.96(1H,m),3.69(3H,s),4.99(1H,d,J=6.6Hz),5.18-5.20(2H,m),7.53(2H,d,J=8.4Hz),7.82(2H,d,J=8.4Hz). IR(CHCl3)3583,3376,3002,2936,2852,1725,1591,1490,1437,1393,1325,1160/cm.[α]D=-8.8°(CHCl3,C=1.00,24℃).No.1a-60CDCl3 300MHz0.96-2.05(24H,m),2.22(1H,m),2.33(2H,m),2.88(1H,m),5.22-5.26(2H,m),5.30(1H,d,J=5.7Hz),7.50(2H,d,J=8.7Hz),7.80(2H,d,J=8.7Hz).IR(CHCl3)3376,3260,3022,2936,2852,1710,1592,1491,1452,1395,1325,1159/cm.[α]D=-8.9°(CHCl3,C=1.06,24℃),mp.88-91℃No.1a-61CDCl3 300MHz0.95-2.24(23H,m),2.29(2H,m),2.99(1H,m),3.69(3H,s),4.76(1H,d,J=6.3Hz),5.21-5.24(2H,m),6.28(1H,m),7.50-7.53(2H,m),7.77- 7.80(2H,m).IR(CHCl3)3374,3270,3018,2942,2868,2196,1726,1589,1490,1435,1324,1158/cm.[α]D=+7.7°(CHCl3,C=1.02,24℃), mp.93-95℃No.1a-62CDCl3 300MHz0.96-2.45(23H,m),2.36(2H,d,J=6.9Hz),2.99(1H,m),5.24(1H,d,J=6.3Hz),5.24-5.32(2H,m),6.28(1H,m),7.50-7.53(2H,m),7.78-7.8 1(2H,m).IR(CHCl3)3468,3374,3260,3020,2942,2868,2196,1598,1490,1455,1398,1322,1157/cm.[α]D=+19.4°(CHCl3,C=1.03,24℃).No.1a-63CDCl3 300MHz0.93-1.95(25H,m),2.16(1H,m),2.29(2H,t,J=7.2Hz),2.43(2H,t,J=6.9Hz),2.94(1H,m),3.69 (3H,s),4.95(1H,d,J=6.9Hz),5.21-5.24(2H,m),7.49(2H,d,J=8.7Hz),7.79(2H,J=8.7Hz). IR(CHCl3)3376,3018,2946,2866,2222,1727,1592,1456,1435,1325,1158/cm.[α]D=+3.7°(CHCl3,C=1.00,25℃).No.1a-64CDCl3 300MHz0.93-1.97(26H,m),2.35(2H,t,J=7.2Hz),2.43(2H,t,J=7.2Hz),3.00(1H,m),5.08(1H,d,J=6.6Hz),5.26-5.27(2H,m),7.49(2H,d,J=8.7Hz),7.78(2H,d,J=8.7Hz).IR(CHCl3)3260,3020,2948,2864,2222,1708,1592,1489,1456,1397,1324,1156/cm.[α]D=+14.4°(CHCl3,C=1.00,25℃) mp.70-71℃.No.1a-65CDCl3 300MHz0.95-1.98(14H,m),2.18(1H,m),2.30(2H,t,J=7.2Hz),3.00(1H,m),3.67(3H,s),4.83(1H,d,J=6.9Hz),5.22-5.25(2H,m),5.54(1H,br),6.82-6.85(2H,m),7.42-7.45(2H,m),7.59-7.62(2H,m),7.82-7.85(2H,m).IR(CHCl3)3576,3374,3018,2946,2868,2208,1725,1607,1587,1514,1435,1325,1270,1162,1133/cm.[α]D=+9.1°(CHCl3,C=1.03,24℃),mp.111-112℃No.1a-66CDCl3 300MHz0.97-2.03(14H,m),2.15(1H,m),2.35(2H,t,J=7.5Hz),3.00(1H,m),5.17(1H,d,J=6.6Hz),5.26-5.30(2H,m),6.82-6.85(2H,m),7.42-7.45(2H,m),7.59-7.62(2H,m),7.82-7.85(2H,m).IR(CHCl3)3260,2948,2870,2208,1709,1607,1587,1514,1396,1325,1270,1162,1133/cm.[α]D=-21.0°(CHCl3,C=1.00,23℃),mp.161-162℃No. 1a-67CDCl3 300MHz0.95-1.98(14H,m),2.20(1H,m),2.29(2H,t,J=7.2Hz),3.01(1H,m),3.67(3H,s),4.82(1H,d,J=6.6Hz),5.19-5.27(2H,m),7.05-7.10(2H,m),7.51-7.56(2H,m),7.61-7.64(2H,m),7.84-7.87(2H,m).IR(CHCl3)3374,3280,3020,2946,2868,2214,1727,1589,1509,1435,1327,1233,1161,1134/cm.[α]D=+6.7°(CHCl3,C=1.01,24℃), mp.84-85℃No.1a-68CDCl3 300MHz0.96-2.01(14H,m),2.15(1H,m),2.34(2H,t,J=6.9Hz),3.02(1H,m),5.23-5.27(3H,m),7.04-7.10(2H,m),7.51- 7.56(2H,m),7.61-7.64(2H,m),7.85- 7.88(2H,m).IR(CHCl3)3374,3258,3020,2948,2868,2214,1708,1589,1509,1455,1398,1322,1156/cm.[α]D=+22.6°(CHCl3,C=1.02,24℃),mp.135-136℃No.1a-69CDCl3 300MHz0.95-1.98(14H,m),2.19(1H,m),2.29(2H,t,J=7.2Hz),2.39(3H,s),3.01(1H,m),3.69(3H,s),4.80(1H,d,J=6.6Hz),5.20-5.29(2H,m),7.18(2H,d,J=8.1Hz),7.44(2H,d,J=8.1Hz),7.62(2H,d,J=8.4Hz),7.84(2H,d,J=8.4Hz).IR(CHCl3)3374,3022,2946,2868,2210,1727,1589,1511,1436,1323,1161,1133/cm.[α]D=+9.2°(CHCl3,C=1.02,24℃).mp.116-118℃No.1a-70CDCl3 300MHz1.15-2.00(14H,m),2.13(1H,m),2.33-2.38(5H,m),3.04(1H,m),5.14(1H,d,J=6.6Hz),5.25-5.30(2H,m),7.17(2H,d,J=7.8Hz),7.44(2H,d,J=7.8Hz),7.62(2H,d,J=8.4Hz),7.85(2H,d,J=8.4Hz).IR(CHCl3)3380,3260,3020,2948,2868,2210,1708,1590,1511,1396,1324,1160,1133/cm.[α]D=+24.6°(CHCl3,C=1.00,24℃).No.1a-71CDCl3 300MHz0.95-1.96(14H,m),2.19(1H,m),2.29(2H,t,J=7.2Hz),3.00(1H,m),3.20(1H,s),3.65(3H,s),4.81 (1H,d,J=6.6Hz),5.20-5.27(2H,m),7.46-7.54(4H,m),7.62-7.65(2H,m),7.85-7.88(2H,m).IR(CHCl3)3374,3290,3018,3002,2946,2868,2212,2110,1726,1591,1507,1435,1401,1324,1161/cm.[α]D=+9.6°(CHCl3,C=1.01,24℃),mp.136-138℃,No.1a-72CDCl3 300MHz0.96-2.01(14H,m),2.14(1H,m),2.35(2H,t,J=7.2Hz),3.05 (1H,m),3.20(1H,s),5.16(1H,d,J=7.2Hz),5.26-5.29(2H,m),7.45-7.53(4H,m),7.63(2H, d,J=8.4Hz),7.87(2H,d,J=8.4Hz).IR(CHCl3)3462,3374,3290,3024,2948,2868,2212,2110,1708,1591,1508,1455,1401,1321,1274,1160,1132/cm.[α]D=+24.3°(CHCl3,C=1.03,24℃),mp.96-99℃No.1a-73CDCl3 300MHz0.95-1.98(14H,m),2.19(1H,m),2.27-2.32(5H,m),3.01 (1H,m),3.67(3H,s),4.80(1H,d,J=6.6Hz),5.20-5.27(2H,m),7.12(2H,m),7.56(2H,m),7.63(2H,m),7.84(2H,m).IR(CHCl3)3374,3276,3018,2946,2868,2214,1762,1730,1589,1506,1435,1368,1161/cm.[α]D=+7.8°(CHCl3,C=1.02,24℃),mp.102-104℃No.1a-74CDCl3 300MHz0.95-2.05(14H,m),2.15 (1H,m),2.32-2.37(5H,m),3.02(1H,m),5.14(1H,d,J=6.6Hz),5.26-5.30(2H,m),7.10-7.13(2H,m),7.54-7.57(2H,m),7.62-7.64(2H,m),7.84-7.87(2H,m).IR(CHCl3)3482,3250,3022,2946,2868,2214,1716,1709,1589,1507,1454,1396,1368,1322,1195,1161/cm.[α]D=+15.0°(CHCl3,C=1.00,24℃),mp.129-131℃No.1a-75CDCl3 300MHz0.95-1.99(14H,m),2.20(1H,m),2.30(2H,t,J=7.2Hz),3.02(1H,m),3.67(3H,s),3.94(3H,s),4.79(1H,d,J=6.6Hz),5.19-5.29(2H,m),7.60-7.63(2H,m),7.65-7.67(2H,m),7.86-7.89(2H,m),8.04-8.06(2H,m).IR(CHCl3)3378,3018,2946,2880,1720,1604,1435,1307,1276,1161,1106/cm.[α]D=+7.3°(CHCl3,C=1.01,25℃),mp.132-133℃No.1a-76CDCl3+CD3OD 300MHz1.04-2.05(14H,m),2.19(1H,m),2.32(2H,t,J=6.9Hz),2.93(1H,m),5.27-5.31(2H,m),7.60-7.63(2H,m),7.65-7.68(2H,m),7.86-7.89(2H,m),8.05-8.07(2H,m).IR(CHCl3)3402,3299,2955,2876,2665,2549,1455,1422,1313,1281,1164/cm.[α]D=-21.1°(CH3OH,C=1.03,23℃),mp.227-229(dec.)No.1a-77CDCl3 300MHz0.96-1.99(14H,m),2.20(1H,m),2.30(2H,t,J=7.2Hz),3.02(1H,m),3.68(3H,s),4.88(1H,d,J=6.3Hz),5.19-5.29 (2H,m),7.67-7.72(4H,m),7.89-7.91(2H,m),8.24-8.27(2H,m). IR(CHCl3)3376,3276,3020,2946,2870,2214,1726,1594,1519,1455,1435,1389,1344,1161/cm.[α]D=+7.7°(CHCl3,C=1.02),mp.87-89℃No.1a-78CDCl3 300MHz 0.98-2.00(14H,m),2.18(1H,m),2.34(2H,t,J=7.2Hz),3.02(1H,m),5.24-5.28(2H,m),5.32(1H,d,J=5.7Hz),7.67-7.72(4H,m),7.89-7.92(2H,m),8.23-8.26(2H,m).IR(CHCl3)3374,3260,2948,2214,1708,1595,1344,1160/cm.[α]D=+23.3°(CHCl3,C=1.00),mp.102-103℃.No.1a-79CDCl3 300MHz0.93-2.02(14H,m),2.13(1H,m),2.36(2H,t,J=7.1Hz),3.05(1H,m),3.84(3H,s),5.18(1H,br),5.27-5.31(2H,m),6.88-6.91(2H,m),7.48-7.50(2H,m),7.60-7.63(2H,m),7.83-7.85(2H,m).IR(CHCl3)3380,3252,3020, 2950,2868,2208,1708,1589,1511,1457,1396,1321,1286,1160/cm.[α]D=+26.7°(CHCl3,C=1.00). mp.75-77℃No.1a-80CDCl3 300MHz0.96-1.99(14H,m),2.21(1H,m),2.30(2H,t,J=7.8Hz),3.02(1H,m),3.68(3H,s), 4.80(1H,d,J=6.6Hz),5.19-5.28(2H,m),7.51-7.77(5H,m), 7.87-7.90(2H,m),8.13(1H,m).IR(CHCl3)3374,3270,3018,2946,2868,2216,1726,1607,1567,1527,1495,1456,1436,1344,1296,1161/cm.[α]D=+7.4°(CHCl3,C=1.00,22℃),mp.68-70℃No.1a-81CDCl3 300MHz0.97-2.01(14H,m),2.16(1H,m),2.34(2H,t,J=7.2Hz),3.01(1H,m),5.22-5.28(3H,m),7.51(1H,m),7.65(1H,m)7.70-7.76(3H,m),7.88-7.91(2H,m),8.12(1H,dd,J=6.9Hz,1.5Hz).IR(CHCl3)3480,3382,3262,3026,2952,2872, 2218,1708,1607,1567,1526,1396,1343,1225,1160/cm.[α]D=+22.0°(CHCl3,C=1.00),mp.92-94℃No.1a-82CDCl3 300MHz0.95-1.98(14H,m),2.20(1H,m),2.29(2H,t,J=7.2Hz),3.01(1H,m ),3.67(3 H,s),4.30(2H,br),4.79(1H,d,J=6.9Hz),5.20-5.29(2H,m),6.71-6. 76(2H,m),7.18(1H,m),7.37(1H,dd,J=7.8,1.2Hz),7.61-7.65(2H,m),7.83-7.87(2H,m).IR(CHCl3)3376,3020,2946,2868,2202,1725,1613,1589,1484,1454,1315,1253,1161/cm.[α]D=+8.9°(CHCl3,C=1.00,22℃). mp.68-70℃No.1a-83CDCl3 300MHz0.97-1.99(14H,m),2.17(1H,m),2.33(2H,t,J=6.9Hz),2.99(1H,m),5.20-5.28(2H,m),5.37(1H,d,J=6.9Hz),6.45(2H,br),6.71-6.76(2H,m),7.19(1H,dd,J=7.8,6.6Hz),7.37(1H,m),7.62(2H,d,J=8. 4Hz),7.85(2H,d,J=8.4Hz).IR(CHCl3)3478,3378,3260,3022,2950,2868,2204,1708,1613,1589,1484,1454,1396,1316,1160/cm.[α]D=+17.1°(CHCl3,C=1.01).No.1a-84CDCl3 300MHz1.00-2.08(14H,m),2.21 (1H,m),2.37(2H,t,J=6.9Hz),3.06(1H,m),3.86 (3H,s),5.29-5.33(2H,m),5.45(1H,d,J=6.6Hz),6.91-6.94(2H,m),7.56- 7.59(2H,m),7.81(1H,d.t,J=8.1Hz),8.04(1H,d.d,J=8. 1&1.8Hz),8.57(1H,d,J=2.1Hz).IR(CHCl3)3492,3254,3028,2954,2202,1708,1597,1512,1344,1291,1250/cm.[α]D=+27.4°(CHCl3,C=0.53,23℃).No.1a-85CDCl3 300MHz0.96-2.05(14H,m),2.20(1H,m),2.35(2H,t,J=6.9Hz),2.99(1H,m),3.84(3H,s),5.22-5.31(3H,m),6.89(2H,d,J=8.7Hz),7.19(1H,brs),7.29(1H,brs),7.45-7.50(3H,m).IR(CHCl3)3478,3378,3020,2950,2868,2202,1708,1606,1511,1421,1311,1287,1248,1155/cm.[α]D=+17.1°(CHCl3,C=1.00,23℃).No.1a-86CDCl3 300MHz1.03-2.05(14H,m),2.21(1H,m),2.37(2H,t,J=6.9Hz),3.04(1H,m),5.29-5.33(2H,m),5.57(1H,d,J=6.3Hz),6.84-6.87(2H,m),7.50-7.53(2H,m),7.79(1H,d,J=8.1Hz),8.03(1H,d,d,J=1.5and8.1Hz),8.57(1H,d,J=1.5Hz).IR(CHCl3)3250,3024,2950,2868,2200,1707,1515,1344,1271,1166,1143/cm.[α]D=+21.2°(CHCl3,C=0.26,22℃).No.1a-87CD3OD 300MHz1.04-2.00(14H,m),2.18 (1H,m),2.26(2H,t,J=5.4Hz),2.93(1H,m),5.19-5.24(2H,m),6.77-6.80(2H,m),7.05(1H,d.d,J=2.1and8.1Hz),7.22(1H,d,J=2.1Hz),7.38-7.42(3H,m).IR(CHCl3)3377,2952,2873,2204,1705,1607,1515,1425,1312,1267,1222,1153/cm.[α]D=-15.6°(CH3OH,C=1.02,22℃).No.1a-88CDCl3 300MHz0.90-1.96(14H,m),2.22-2.31(3H,m),2.95(1H,m),3.65(3H,s),4.87(1H,d,J=6.6Hz),5.13-5.28(2H,m),7.46-7.62(3H,m),7.82-7.89(4H,m),7.90-7.96(2H,m),8.42(1H,brs).IR(CHCl3)3376,3016,2946,2868,1720,1677,1592,1514,1498,1429,1376,1314,1241,1156,1094 /cm.[α]D=-10.7°(CHCl3,C=1.04,22.0℃) mp.134-136℃No.1a-89CDCl3+CD3OD 300MHz0.96-2.08(14H,m),2.23(1H,m),2.28(2H,t,J=7.2Hz),2.89(1H,m),5.20-5.32(2H,m),7.46-7.62(3H,m),7.82-7.97 (6H,m).IR(KBr)3272,3007,2952,2874,1708,1660,1592,1527,1498,1433,1400,1317,1260,1152,1094/cm.[α]D=-24.4°(CH3OH,C=1.02,25.0℃).No.1a-90CDCl3 300MHz0.89-1.96(14H,m),2.23-2.33(3H,m),2.92(1H,m),3.67(3H,s),4.85(1H,d,J=6.3Hz),5.10-5.25(2H,m),7.81-7.90(4H,m),8.10-8.18(2H,m),8.31-8.40(2H,m),8.77(1H,s).IR(CHCl3)3372,3018,2946,2868,1718,1685,1592,1527,1436,1397,1346,1318,1256,1154,1099/cm.[α]D=-16.1°(CHCl3,C=1.00,23.0℃).No.1a-91CDCl3+CD3OD 300MHz0.94-2.02(14H,m),2.18-2.36(3H,m),2.87(1H,m),5.15-5.30(2H,m),7.82-7.92(4H,m),8.09-8.16(2H,m),8.30-8.37(2H,m).IR(KBr)3284,3112,3006,2952,2874,1707,1593,1528,1498,1399,1348,1320,1259,1153,1093/cm.[α]D=-26.3°(CH3OH,C=1.01,22℃).No.1a-92CDCl3 300MHz0.93-1.95(14H,m),2.22-2.31(3H,m),2.98(1H,m),3.68(3H,s),5.07(1H,d,J=6.9Hz),5.10-5.24(2H,m),7.18(1H,m),7.35-7.43(2H,m),7.70(2H,d,J=7.8Hz),7.88-8.05(4H,m),8.50(1H,brs).IR(CHCl3)3382,3008,2952,1720,1675,1599,1525,1499,1438,1321,1253,1161,1087/cm.[α]D=-16.6°(CHCl3,C=1.03,24.0℃) mp.100-101℃No.1a-93CDCl3+CD3OD 300MHz0.96-2.00(14H,m),2.18-2.35(3H,m),2.90(1H,m),5.15-5.30(2H,m),7.18(1H,m),7.33-7.42(2H,m),7.65-7.74(2H,m),7.90-8.08(4H,m).IR(KBr)3347,3194,3011,2955,2875,1706,1650,1602,1544, 1499,1443,1325,1265,1165,1091/cm.[α]D=-19.4°(CH3OH,C=1.00,24.0℃) mp.158-159℃No.1a-94CD3OD300MHz1.05-2.00(14H,m),2.14 (1H,m),2.23(2H,t,J=7.2Hz),2.98(1H,m),3.80(3H,s),5.13-5.27(2H,m),6.88-6.98(2H,m),7.54-7.64(2H,m),7.94-8.12(4H,m).IR(KBr)3370,3006,2953,1708,1649,1604,1541,1512,1460,1441,1414,1328,1302,1248,1162,1107,1090,1032/cm.[α]D=-19.1°(CH3OH,C=1.01,24℃).No.1a-95CD3OD300MHz1.04-2.02(14H,m),2.14(1H,m),2.23(2H,t,J=7.2Hz),2.93-3.02(7H,m),5.13-5.27(2H,m),6.82-6.92 (2H,m),7.51-7.59(2H,m),7.95-8.02(2H,m),8.04-8.11(2H,m).IR(KBr)3370,3006,2953,1708,1649,1604,1541,1512,1460,1441,1414,1328,1302,1248,1162,1107,1090,1032/cm.[α]D=-17.6°(CH3OH,C=1.01,24℃).No.1a-96CD3OD300MHz1.05-2.02(14H,m),2.14(1H,m),2.23(2H,t,J=7.2Hz),2.98(1H,m),5.13-5.27(2H,m),6.75-6.84(2H,m),7.43-7.52(2H,m),7.94-8.12(4H,m).IR(KBr)3339,3197,2953,2875,1707,1644,1606,1541,1514,1446,1325,1293,1259,1240,1225,1161,1091/cm.[α]D=-18.7°(CH3OH,C=1.00,24℃). mp.193-196℃No.1a-97d6-DMSO 300MHz1.05-2.08(15H,m),2.15(2H,t,J=7.5Hz),2.89(1H,m),5.18-5.28(2H,m),6.78-7.12(3H,m),7.73(1H,d.d,J=1.4and7.8Hz),7.91-7.95(3H,m),8.14(2H,d,J=8.4Hz),9.71(1H,s).IR(KBr)3407,3191,2953,1711,1646,1614,1603,1537,1457,1326,1162,1151/cm.[α]D=-20.7°(CH3OH,C=1.01,21℃).No.1a-98CDCl3 300MHz0.93-2.00(14H,m),2.21(1H,m),2.31(2H,t,J=7.2Hz),2.93(1H,m),3.84(3H,s),3.85(6H,s),5.15-5.30(2H,m),5.45(1H,d,J=6.3Hz),7.04 (2H,s),7.78-7.86(2H,m),7.90-7.98(2H,m),8.58(1H,s).IR(CHCl3)3264,3008,2954,2874,1707,1670,1607,1537,1506,1451,1421,1308,1158,1129,1088/cm.[α]D=-7.2°(CHCl3,C=1.01,23.5℃).mp.147-149℃.No.1a-99CD3OD 300MHz1.04-1.98(14H,m),2.21(1H,m),2.10(2H,t,J=7.2Hz),2.95(1H,m), 3.76(3H,s),3.86(6H,s),5.07-5.24 (2H,m),7.19(2H,s),7.99(2H,d,J=8.7Hz),8.13(1H,d,J=8.7Hz).IR(KBr)3354,3002,2950,2874,1656,1607,1570,1508,1452, 1413,1314,1233,1185,1157,1127,1092/cm.[α]D=-20.3°(CH3OH,C=1.00,23.5℃).No.1a-100CDCl3 300MHz1.14-1.97(14H,m),2.19(1H,m),2.28(2H,t,J=7.4Hz),3.04(1H,m),3.69(3H,s),5.03(1H,d,J=6.9Hz),5.15-5.29(2H,m),7.65(2H,d,J=8.4Hz), 7.87 (1H,s),7.98(2H,d,J=8.4Hz).IR(CHCl3)3386,3271,3025,3015,2955,2877,1755,1712,1608,1331,1162/cm.[α]D=-29.4°(CH3OH,C=1.01,25℃).No.1a-101d6-DMSO1.00-2.20(17H,m),2.84(1H,m),5.00-5.20(2H,m),7.78(2H,d,J=8.2Hz),7.84(1H,s),7.89-7.95(3H,m).IR(KBr)3269,3065,3008,2952,2874,2763,1746,1707,1607,1322,1157/cm.[α]D=-26.2°(CH3OH,C=1.01,25℃).No.1a-102CD3OD1.00-2.25(17H,m),2.92(1H,s),3.64(3H,s),5.07-5.21(2H,m),7.53(1H,s),7.77(2H,d,J=8.6Hz),7.90(2H,d,J=8.6).IR(KBr)3430,3277,3006,2952,2873,1720,1687,1620,1571,1438,1312,1156 /cm.[α]D=-27.3°(CH3OH,C=0.51,26℃),mp 230-232℃.No.1a-103CDCl3 300MHz0.94-1.96(14H,m),2.19(1H,m),2.28(2H,t,J=7.2Hz),3.04 (1H,m),3.69(3H,s),5.11(1H,d,J=6.6Hz),5.15-5.28(2H,m),7.60(2H,d,J=8.4Hz),7.67(1H,s),7.98(2H,d,J=8.4Hz).IR(CHCl3)3381,3021,2955,2876,1735,1605,1437,1411,1325,1231,1177/cm.[α]D=+8.6°(CHCl3,C=1.00,23℃).No.1a-104CDCl3 300MHz0.94-1.96(14H,m),2.21(1H,m),2.31(2H,t,J=6.8Hz),2.99(1H,m),5.18-5.28(2H,m),5.45(1H,d,J=6.6Hz),7.61(2H,d,J=8.7Hz),7.67(1H,s),7.99 (2H,d,J=8.7Hz).IR(CHCl3)3382,3222,3028,3019,2957,2876,1736,1709,1604,1412,1322,1301,1286,1179,1162/cm.[α]D=+10.4°(CHCl3,C=1.00,23℃).No.1a-105CDCl3 300MHz0.92-1.98(14H,m),2.17(1H,m),2.26(2H.d,J=7.5Hz),3.01(1H,m),3.69(3H,s),4.01(3H,s),4.84(1H,d,J=6.3Hz),5.14-5.30(2H,m),7.71(2H,d,J=8.7Hz),7.87(2H,d,J=8.7Hz),8.09(1H,s).IR(CHCl3)3385,3284,3025,3015,2954,2877,2821,1730,1598, 1459,1438,1403,1341,1160,1052/cm.[α]D=+3.6°(CHCl3,C=1.00,26℃).No.1a-106CDCl3 300MHz0.92-2.08(14H,m),2.14(1H,m),2.34(2H,d,J=7.2Hz),3.02(1H,m),4.01(3H,s),5.19(1H,d,J=6.9Hz),5.23-5.32(2H,m),7.71(2H,d,J=8.4Hz),7.88(2H,d,J=8.4Hz),8.09(1H,s).IR(CHCl3)3510,3384,3268,3028,3021,3014,2957,2877,2821,2667,2821,2666,1707,1598,1459,1404,1341,1324,1160,1052/cm.[α]D=+11.8°(CHCl3,C=1.01,25℃)、mp 955-96℃No.1a-107CDCl3 300MHz0.92-1.97(14H,m),1.34(3H,t,J=7.2Hz),2.18(1H,m),2.28(2H.d,J=7.4Hz),3.01 (1H,m),3.68(3H,s),4.26(2H,q,J=7.2Hz),4.86(1H,d,J-6.6Hz),5.15-5.29(2H,m),7.71(2H,d,J=8.7Hz),7.87(2H,d,J=8.7Hz),8.09(1H,s).IR(CHCl3)3385,3282,3025,3026,3015,2954,2877,1729,1599,1480,1458,1438,1403,1338,1161/cm.[α]D=+4.4°(CHCl3,C=1.00,25℃).No.1a-108CDCl3 300MHz0.90-2.04(14H,m),1.34(3H,t,J=7.2Hz),2.14(1H,m),2.34 (2H, d,J=7.1Hz),3.01(1H,m),4.27 (2H,q,J=7.2Hz),5.20(1H,d,J=6.6Hz),5.21-5.35(2H,m),7.71(2H,d,J=8.4 Hz),7.88(2H,d,J=8.4Hz),8.10(1H,s).IR(CHCl3)3514,3384,3270,3025,3015,3015,2957,2877,1708.1599,1458,1403,1324,1324,1160,1050/cm.[α]D=+12.7°(CHCl3,C=1.00,25℃).No.1a-109[α]D=+8.5°(CHCl3,C=1.00,25℃).mp109.0-111.0℃No.1a-110CDCl3∶CD3OD(95∶5)0.92-2.06(14H,m),2.20(1H,m),2.30(2H,d,J=7.2Hz),2.99(1H,m),5.22-5.33(2H,m),7.54-7.66 (3H,m),8.07(2H,d,J=9.0Hz),8.12-8.20(2H,m),8.29 (2H,d,J=9.0Hz).IR(Nujol)3270,2956,2924,2854,1716,1548,1485,1319,1167/cm.[α]D=+17.0°(CHCl3,C=1.00,25℃). mp.166.5-168℃No.1a-111[α]D=+2.6°(CHCl3,C=1.00,24℃).mp120.0-121.0℃No.1a-112CDCl3 300MHz0.96-2.04(14H,m),2.19(1H,m),2.33(2H,d,J=7.1Hz),3.07(1H,m),5.28-5.31(2H,m),5.33(1H,d,J=6.6Hz),7.54-7.63(3H,m),8.05(2H,d,J=8.4Hz),8.18-8.23(2H,n),8.41 (2H,d,J=8.4Hz).IR(CHCl3)3384,3269,3025,3015,2957,2877,1708,1598,1496,1457,1417,13261164 /cm.[α]D=+12.2°(CHCl3,C=1.00,24℃). mp.163-164℃No.1a-113[α]D=+22.1°(CHCl3,C=1.05,25℃). mp.90-92℃No.1a-114[α]D=+2.2°(CHCl3,C=1.02,25℃).No.1a-115CDCl3 300MHz0.90-1.98(14H,m),2.15-2.22(1H,m),2.27(2H,t,J=7.2Hz),2.95-3.04(1H,m),3.68(3H,s),4.04(2H,s),4.85(1H,d,J=6.6Hz),5.10-5.27(2H,m),7.12-7.34(7H,m),7.76-7.82(2H,m).IR(CHCl3)3384,3026,2952,1727,1595,1493,1436,1318,1155,1091,890/cm.[α]D=0 °[α]436=+4.9±0.4°(CHCl3,C=1.05,23℃)No.1a-116CDCl3 300MHz0.90-2.10(14H,m),2.10-2.18(1H,m),2.32(2H,t,J=7.2Hz),2.96-3.04(1H,m),4.04(2H,s),5.14(1H,d,J=6.6Hz),5.16-5.28(2H,m),7.12-7.34(7H,m),7.76-7.82(2H,m).IR(CHCl3)3260,3020,2950,1709,1407,1318,1154,1091,892/cm.[α]D=+9.1±0.5°(CHCl3,C=1.04,23℃)No.1a-117CD9OD 300MHz0.96-2.18(17H,m),2.89-2.92(1H,m),4.05 (2H,s),4.95-5.22(2H,m),7.15-7.42 (7H,m),7.75-7.81(2H,m).IR(KBr)3429,3279,2951,2872,1563,1494,1453,1408,1313,1155,1093,1057/cm.[α]D=-16.3±0.5°(CH3OH,C=1.06,25℃)No.1a-118CDCl3 300MHz0.98-1.70(15H,m),1.80-2.00(5H,m),2.20-2.40(3H,m),2.98(1H,m),4.06(2H,s),4.72(1H,d,J=6.3Hz),5.00-5.23(3H,m),7.16(2H,d,J=8.4Hz),7.26-7.33(5H,m),7.79(2H,d,J=8.1Hz).IR(CHCl3)3376,3020,2948,2868,1716,1596,1492,1453,1407,1318,1155,1105/cm.[α]D=+2.4°(CHCl3,C=1.08,24℃).No.1a-119CDCl3 300MHz0.90-2.02(14H,m),2.20(1H,m),2.29(2H,t,J=7.2Hz),3.00(1H,m),3.68(3H,s),4.86 (1H,d,J=6.9Hz),5.13-5.34(2H,m),7.00-7.09(4H,m),7.22(1H,m),7.37,7.45(2H,m),7.79-7.86(2H,m).IR(CHCl3)3376,3018,2946,2868,1727,1582,1486,1321,1243,1151,1093/cm.[α]D=+4.5°(CHCl3,C=1.05,23.5℃).No.1a-120CD3OD 300MHz1.00-2.00(14H,m),2.13(2H,t,J=7.5Hz),2.16(1H,m),2.91(1H,m),5.05-5.33(2H,m),7.04-7.11(4H,m),7.18-7.25 (1H,m),7.38-7.48(2H,m),7.80-7.87(2H,m).IR(KBr)3430,3278,3006,2952,2873,1583,1487,1410,1322,1298,1245,1152,1095/cm.[α]D=-8.8°(CH3OH,C=1.05,25.0℃).No.1a-121CDCl3 300MHz0.90-2.10(14H,m),2.15(1H,m),2.35(2H,t,J=7.2Hz),3.01(1H,m),5.20(1H,d,J=6.9Hz),5.22-5.35(2H,m),7.00-7.09(4H,m),7.18-7.25(1H,m),7.37-7.45(2H,m),7.79-7.86(2H,m).IR(CHCl3)3260,3020,2948,2868,1708,1582,1486,1409,1321,1296,1243,1151,1093/cm.[α]D=+13.1°(CHCl3,C=1.04,24.0℃).No.1a-122CDCl3 300MHz0.90-2.00(14H,m),2.23(1H,m),2.28(2H,t,J=7.5Hz),2.96 (1H,m),3.67(3H,s),4.69(1H,d,J=6.6Hz),5.15-5.32(2H,m),6.22(1H,s),6.98- 7.40(5H,m),7.30- 7.38(2H,m),7.68-7.74(2H,m).IR(CHCl3)3416,3370,3018,2946,2868,1725,1587,1508,1437,1400,1320,1149,1094/cm.[α]D=+6.2°(CHCl3,C=1.04,25.0℃).No.1a-123CDCl3 300MHz0.90-2.04(14H,m),2.18(1H,m),2.33(2H,t,J=7.2Hz),2.96(1H,m),5.04-5.35(3H,m),6.98-7.12(3H,m),7.12-7.20(2H,m),7.28-7.38(2H,m),7.66-7.74(2H,m).IR(CHCl3)3424,3270,3028,2952,2872,1708,1587,1508,1445,1399,1320,1148,1092/cm.[α]D=+20.9°(CHCl3,C=1.06,23.0℃).No.1a-124CDCl3 300MHz0.90-2.00(14H,m),2.18(1H,m),2.28(2H,t,J=7.2Hz),3.00(1H,m),3.14(3H,s),3.68(3H,s),4.56(2H,s),4.84(1H,d,J=6.3Hz),5.10-5.29 (2H,m),7.16-7.26(4H,m),7.26-7.34(2H,m),7.78-7.84(2H,m).IR(CHCl3)3384,3028,2952,2874,1727,1598,1501,1435,1410,1370,1329,1172,1148,1091/cm.[α]D=+2.7°(CHCl3,C=1.09,23.0℃).No.1a-125CDCl3 300MHz0.90-2.00(14H,m),2.18(1H,m),2.28(2H,t,J=7.2Hz),2.29(3H,s),3.00(1H,m),3.68(3H,s),4.04(2H,s),4.80(1H,d,J=6.6Hz),5.11-5.29(2H,m),6.99-7.06(2H,m),7.12-7.19(2H,m),7.31(2H,d,J=8.1Hz),7.79(2H,d,J=8.1Hz).IR(CHCl3)3382,3280,3024,2950,2874,1730,1596,1504,1435,1407,1367,1318,1196,1155,1091/cm.[α]D=+2.9°(CHCl3,C=1.06,23.0℃).No.1a-126CDCl3 300MHz0.90-2.02(14H,m),2.14(1H,m),2.29(3H,s),2.32(2H,t,J=7.2Hz),3.01(1H,m),4.03(2H,s),5.10(1H,d,J=6.6Hz),5.15-5.30(2H,m),6.98-7.06(2H,m),7.11-7.18(2H,m),7.30(2H,d,J=8.1Hz),7.79(2H,d,J=8.1Hz).IR(CHCl3)3374,3260,3020,2948,2868,1749,1708,1596,1504,1407,1369,1317,1195,1155,1091 /cm.[α]D=+10.0°(CHCl3,C=1.09,23.0℃).No.1a-127CDCl3 300MHz0.87-1.95(14H,m),2.18-2.32(3H,m),2.95(1H,m),3.69(3H,s),3.96(2H,s),4.79(1H,d,J=6.6Hz),4.97-5.17(2H,m),5.54(1H,s),6.75-6.82(2H,m),6.97-7.05(2H,m),7.25-7.33(2H,m),7.75-7.81(2H,m).IR(CHCl3)3382,3026,2950,2874,1722,1595,1511,1436,1407,1317,1257,1154,1090/cm.[α]D=-2.1°(CHCl3,C=1.00,21.5℃).No.1a-128CDCl3 300MHz0.85-2.02(14H,m),2.18(1H,m),2.31(2H,t,J=7.2Hz),2.96(1H,m),3.95(2H,s),5.05-5.27(3H,m),6.73-6.82(2H,m),6.96-7.04(2H,m),7.25-7.32(2H,m),7.74-7.81(2H,m).IR(CHCl3)3262,3020,2948,2868,1708,1596,1511,1407,1315,1242,1154,1091/cm.[α]D=+4.8°(CHCl3,C=1.04,22℃).No.1a-129CDCl3 300MHz0.89-1.98(14H,m),2.18(1H,m),2.27(2H,t,J=7.2Hz),2.99(1H,m),3.68(3H,s),3.79(3H,s),3.98(2H,s),4.81(1H,d,J=6.6Hz),5.10-5.27(2H,m),6.81-6.87(2H,m),7.03-7.10(2H,m),7.25-7.32(2H,m),7.75-7.82(2H,m).IR(CHCl3)3382,3276,3006,2950,2874,1726,1609,1509,1457,1436,1407,1315,1244,1154,1091,1033/cm.[α]D=+19.3°(CHCl3,C=1.05,23℃).No.1a-130CDCl3 300MHz0.90-2.00(14H,m),2.20(1H,m),2.30(2H,t,J=7.2Hz),2.98(1H,m),3.69(3H,s),4.81(1H,d,J=6.6Hz),5.12-5.32(2H,m),546(1H,brs),6.84- 7.01(6H,m),7.76-7.83(2H,m)IR(CHCl3)3380, 3284,3024,2952,2874,1724,1588,1504,1488,1436,1321,1296,1149,1091/cm.[α]D=+28.9°(CHCl3,C=1.01,23℃).No.1a-131CDCl3 300MHz0.92-2.10(14H,m),2.18(1H,m),2.34(2H,t,J=6.9Hz),2.96(1H,m),5.18-5.35(3H,m),6.84-7.01 (6H,m),7.75-7.83(2H,m).IR(CHCl3)3270,3028, 2952,2874,1708,1589,1505, 1489,1456, 1322,1297,1238,1148,1091/cm.[α]D=+7.7°(CHCl3,C=1.09,24℃).No.1a-132CDCl3 300MHz0.91-2.02(14H,m),2.19(1H,m),2.29(2H,t,J=7.2Hz),2.99(1H,m),3.68(3H,s),3.83(3H,s),4.82(1H,d,J=6.6Hz),5.14-5.33(2H,m),6.90-7.04(6H,m),7.76-7.83(2H,m).IR(CHCl3)3384,3006,2952,2874,1727,1589,1502,1488,1459,1438,1321,1295,1231,1150,1092,1033/cm.[α]D=+3.1°(CHCl3,C=1.01,23℃).No.1a-133TLC Rf=0.21 (乙酸乙酯/正已烷=1∶1(0.3%乙酸))No.1a-134CDCl3 300MHz0.97-2.10(14H,m),2.20(1H,m),2.36(2H,t,J=6.9Hz),3.04(1H,m),5.22-5.33(2H,m),5.41(1H,d,J=6.6Hz),7.02(1H,d,J=9.0Hz),7.09-7.13(2H,m),7.26-7.32(1H,m),7.43-7.49(2H,m),7.93(1H,d.d,J=2.4and9.0Hz),8.46(1H,d,J=2.4Hz).IR(CHCl3)3384,3270,3020,2958,1709,1610,1587,1537,1479,1352,1271,1252,1167/cm.[α]D+20.9°(CHCl3,C=0.51,22℃).No.1a-135CDCl3 300MHz0.96-2.02(14H,m),2.21(1H,m),2.29(2H,t,J=7.2Hz),3.07(1H,m),3.68(3H,s),5.04(1H,d,J=6.9Hz),5.16-5.33(2H,m),7.48-7.55(2H,m),7.64(1H,m),7.76-7.82(2H,m),7.88-7.94(2H,m),7.98-8.04(2H,m).IR(CHCl3)3384,3282,3026,2952,2874,1727,1663,1596,1446,1396,1316,1274,1163,1090/cm.[α]D=+3.1°(CHCl3,C=1.03,22.0℃).No.1a-136CDCl3 300MHz0.95-2.05(14H,m),2.19(1H,m),2.34(2H,t,J=7.2Hz),3.08(1H,m),5.10-5.40(2H,m),5.35(1H,d,J=6.8Hz),7.45-7.58(2H,m),7.64(1H,m),7.74-7.84(2H,m),7.84-7.95(2H,m),7.95-8.06(2H,m).IR(CHCl3)3260,3018,2950,2870,1708,1662,1595,1446,1395,1316,1274,1162,1090/cm.[α]D=+12.9°(CHCl3,C=1.05,21.5℃).No.1a-137CDCl3 300MHz0.97-2.04(14H,m),2.27(1H,m),2.31(2H,t,J=7.2Hz),3.07(1H,m),3.70(3H,s),5.15-5.30(3H,m),7.48- 7.68(5H,m),7.96-8.02(2H,m).IR(CHCl3)3382,3030,2952,2878,1725,1446,1329,1154,1098/cm.[α]D=-12.1°(CHCl3,C=1.03,22.0℃).No.1a-138CDCl3 300MHz0.95-2.04(14H,m),2.25(1H,m),2.35(2H,t,J=7.2Hz),3.08(1H,m),5.15-5.34(2H,m),5.41(1H,d,J=6.6Hz),7.48-7.68(5H,m),7.98-8.03(2H,m).IR(CHCl3)3370,3242,3022,2950,2870,1707,1445,1408,1329,1154,1099/cm.[α]D=-0.6°(CHCl3,C=1.06,21.5℃) [α]365+30.7°(CHCl3,C=1.06,21.5℃).No.1a-139CDCl3 300MHz0.92-2.19(14H,m),2.27-2.34(3H,m),3.26(1H,m),3.65(3H,s),4.28(2H,s),4.37(1H,d,J=7.4Hz),5.34-5.50(2H,m),7.37-7.62(9H,m).IR(CHCl3)3389,3294,3028,3015,2954,2877,1730,1600,1488,1325,1151,1129/cm.[α]D=-24.8°(CHCl3,C=1.01,24℃).No.1a-140CDCl3 300MHz0.92-2.22(15H,m),2.34(2H,t,J=7.1Hz),3.24 (1H,m),4.29(2H, s),4.81(1H,d,J=7.4Hz),5.32-5.52(2H,m),7.36-7.62(9H,m).IR(CHCl3)3510,3388,3251,3031,3015,2956,2877,2668,1708,1601,1488,1318,1151,1129/cm.[α]D=-24.6°(CHCl3,C=1.02,25℃).No.1a-141CDCl3 300MHz0.92-2.19(15H,m),2.32(2H,t,J=7.2Hz),3.26(1H,m),3.65(3H,s),4.31 (2H,s),4.48(1H,d,J=7.4Hz),5.33-5.49(2H,m),7.42-7.80(8H,m).IR(CHCl3)3388,3285,3018,2955,2877,2225,1730,1597,1479,1320,1152,1129/cm.[α]D=-20.1°(CHCl3,C=0.96,25℃).No.1a-142CDCl3 300MHz0.92-2.22(15H,m),2.35(2H,t,J=6.8Hz),3.25(1H,m),4.32(2H,s),4.86(1H,d,J=7.4Hz),5.33-5.53(2H,m),7.43-7.80(8H,m).IR(CHCl3)3512,3388,3258,3031,3023,3014,2956 2877,2225,1708,1597,1479,1319,1151,1128/cm.[α]D=-19.3°(CHCl3,C=1.09,23℃).No.1a-143CDCl3 300MHz1.00-1.93(14H,m),2.17(1H,m),2.27(2H,t,J=7.2Hz),3.07(1H,m),5.17-5.22(2H,m),5.36(1H,d,J=6.9Hz),7.77(1H,d,J=9.0Hz),8.11-8.17(2H,m),8.36(1H,d.d,J=2.1and9.0Hz),8.51(1H,d,J=1.8Hz),8.65(1H,d,J=2.1Hz).IR(CHCl3)3382,3266,3026,2954,2874,1708,1632,1585,1528,1458,1419,1345,1153/cm.[α]D=+7.6°(CHCl3,C=1.04,22℃).No.1a-144CDCl3 300MHz0.95-1.90(14H,m),2.17(1H,m),2.25(2H,t,J=7.5Hz),3.02(1H,m),5.09(1H,d,J=6.6Hz),5.15-5.21(2H,m),6.72(1H,d,J=8.4Hz),6.85(1H,s),7.54 (1H,d,J=8.4Hz),7.72(1H,d,J=9.0Hz),7.83(1H,d.d,J=1.8and9.0Hz),8.32(1H,d,J=1.8Hz).IR(CHCl3)3380,3260,3022,2948,2868,2352,1709,1636,1460,1425,1313,1291,1265,1148,1130/cm.[α]D=+12.9°(CHCl3,C=1.02,22.5℃).No.1a-145CDCl3 300MHz0.97-1.90(14H,m),2.15(1H,m),2.27(2H,t,J=6.9Hz),3.02(1H,m),3.08(6H,s),5.12(1H,d,J=6.3Hz),5.19-5.25(2H,m),6.78-6.84(2H,m),7.53(1H,d,J=8.7Hz),7.76-7.83(2H,m),8.30(1H,d,J=1.8Hz).IR(CHCl3)3272,3030,2950,2874,1708,1635,1601,1511,1457,1425,1357,1328,1151,1124/cm.[α]D=+6.3°(CHCl3,C=1.04,23℃).No.1a-146CDCl3 300MHz0.95-2.00(14H,m),2.16(1H,m),2.29(2H,t,J=7.2Hz),3.05(1H,m),4.10(3H,s),5.13-5.28(2H,m),5.38(1H,d,J=6.9Hz),7.67-7.74(2H,m),8.08(1H,d.d,J=1.8and9.0Hz),8.11(1H,s),8.61(1H,d,J=1.8Hz).IR(CHCl3)3260,3020,2948,2868,1708,1639,1606,1528,1470,1455,1424,1349,1311,1238,1174,1149,1120,1079,1060,1022/cm.[α]D=+7.8°(CHCl3,C=1.00,23℃).No.1a-147CDCl3 300MHz0.92-1.92(14H,m),2.17(1H,m),2.25(2H,t,J=7.2Hz),3.01(1H,m),3.97(3H,s),5.10-5.27(5H,m),6.92(1H,s),7.29(1H,s),7.52(1H,d,J=8.7Hz),7.82(1H,d.d,J=2.1and8.7Hz),8.33(1H,d,J=2.1Hz).IR(CHCl3)3380,3264,3002,2950,2868,1708,1634,1476,1452,1426,1317,1264,1218,1169,1147,1115,1068,1031/cm.[α]D=+5.6°(CHCl3,C=1.02,23℃).No.1a-148CDCl3 300MHz0.90-1.98(14H,m),2.15(1H,m),2.28(2H,t,J=6.9Hz),2.91 (6 H s),3.03(1H,m),4.01(3H,s),5.15-5.26(3H,m),7.18(1H,s),7.38(1H,s),7.59(1H,d,J=8.7Hz),7.87(1H,d.d,J=2.1和8.7Hz),8.40(1H,d,J=2.1Hz).IR(CHCl3)3384,3266,2956,1709,1632,1602,1495,1473,1458,1430,1317,1231,1148,1121/cm.[α]D=+11.2°(CHCl3,C=1.01,23℃).No.1a-149CDCl3 300MHz0.99-1.90(14H,m),2.17(1H,m),2.28(2H,t,J=7.2Hz),3.00(1H,m),5.13-5.19(2H,m),5.43(1H,d,J=6.0Hz),7.02(1H,d.d,J=2.4和9.0Hz),7.38-7.41(2H,m),7.58(1H,d,J=8.7Hz),7.96(1H,d.d,J=1.8和8.7Hz),8.45(1H,d,J=1.8Hz).IR(CHCl3)3270,3020, 2948,2868,1709,1601,1478,1448,1419,1315,1147,1120/cm.[α]D=-11.4°(CHCl3,C=1.01,23℃).No.1a-150CDCl3 300MHz0.97-1.88(14 H,m),2.12-2.31(3H,m),2.38(3H,s),3.01(1H,m),5.14-5.19(2H,m),5.36(1H,d,J=6.6Hz),7.24(1H,d.d,J=2.4和9.0Hz),7.59(1H,d,J=6.3Hz),7.66(1H,d,J=8.7Hz),7.72(1H,d,J=2.4Hz),8.01(1H,d.d,J=1.8和8.7Hz),8.49(1H,d,J= 1.8Hz).IR(CHCl3)3470,3374,3260,3018,2950,2868,1709,1474,1444,1412,1370,1319,1266,1162,1145,1118/cm.[α]D=+4.9°(CHCl3,C=1.00,24℃).No.1a-151CDCl3 300MHz0.97-1.89(14H,m),2.17(1H,m),2.25(2H,t,J=7.2Hz),3.03 (1H,m),3.92(3H,s),5.15-5.20(2H,m),5.32(1H,d,J=6.6Hz),7.11(1H,d.d,J=2.4and9.3Hz),7.45(1H,d,J=2.4Hz),7.50(1H,d,J=9.3Hz),7.62(1H,d,J=8.7H),7.97(1H,d.d,J=2.1and8.7Hz),8.50(1H,d,J=2.1Hz).IR(CHCl3)3260,3018,2948,1708,1483,1454,1432,1314,1287,1268,1188,1169,1147/cm.lα]D=+4.9°(CHCl3,C=1.01,23.5℃).No.1a-152CDCl3 300MHz0.98-2.04(14H,m),2.15(1H,m),2.30(2H,t,J=6.6Hz),3.04 (1H,m),5.17-5.29(3H,m),7.41(1H,d.d,J=1.5and8.1Hz),7.64-7.68(2H,m),7.92(1H,d,J=8.4Hz),8.00(1H,d.d,J=1.8and8.4Hz),8.49(1H,d,J=1.8Hz).IR(CHCl3)3266,3028,2952,2872,1707,1629,1591,1456,1416,1318,1275,1150/cm.[α]D=+3.2°(CHCl3,C=1.04,23℃).No.1a-153CDCl3 300MHz0.97-1.88(14H,m),2.16(1H,m),2.26 (2H,t,J=7.2Hz),3.03 (1H,m),4.64-4.65(2H,m),5.16-5.50(5H,m),6.13(1H,m),7.14(1H,d.d,J=2.7and9.0Hz),7.46-7.52(2H,m),7.63(1H,d,J=8.7Hz),7.97(1H,d.d,J=1.8and8.7Hz),8.49(1H,d,J=1.8Hz).IR(CHCl3)3374,3260,3020,2948,2868,1708,1599,1478,1446,1414,1314,1284,1268,1184,1148,1120/cm.[α]D=+5.3°(CHCl3,C=1.00,23℃).No.1a-154CDCl3 300MHz0.99-2.00(15H,m),2.26(2H,t,J=7.2Hz),3.03(1H,m),4.07(3H,s),5.23-5.27(2H,m),5.36(1H,d,J=7.2Hz),7.20(1H,s),7.36-7.48(2H,m),7.55-7.58(1H,m),7.91-7.93(1H,m),8.52(1H,s).IR(CHCl3)3362,3257,3020,2948,2868,1708,1637,1602,1579,1488,1457,1437,1413,1345,1318,1301,1276,1182,1104/cm.[α]D=+19.4°(CHCl3,C=1.01,25℃).mp.88-90℃No.1a-155CDCl3 300MHz0.92-2.02(14H,m),2.15(1H,m),2.31 (2H,t,J=7.2Hz),3.01(1H,m),4.10(2H,s),5.10(1H,d,J=6.6Hz),5.18-5.35(2H,m),7.04-7.26(5H,m),7.67-7.76(2H,m).IR(CHCl3)3266,3028,2952,2952,2872,1708,1599,1574,1478,1457,1418,1301,1258,1147,1124,1101,1080/cm.[α]365 +33.4°(CHCl3,C=1.00,23℃).No.1a-156CDCl3 300MHz0.91-2.21(15H,m),2.33(2H,t,J=6.9Hz),3.01(1H,m),5.11(1H,d,J=6.6Hz),5.27-5.35(2H,m),6.85-6.96(5H,m),7.35(1H,d,J=2.1Hz),7.42(1H,d.d,J=2.1and8.7Hz).IR(CHCl3)3384,3263,2957,1708,1587,1489,1462,1416,1290,1222,1151,1123/cm.[α]D=+6.4°(CHCl3,C=1.00,23℃).No.1a-157CDCl3 300MHz0.97-1.91(14H,m),2.18(1H,m),2.26(2H,t,J=6.9Hz),3.04(1H,m),5.18-5.26(3H,m),7.52-7.56(2H,m),7.88-8.00(3H,m),8.25(1H,m),8.69(1H,m).IR(CHCl3)3382,3268,2952,2874,1707,1457,1425,1409,1318,1152/cm.[α]D=+4.4°(CHCl3,C=1.02,22℃). No.1a-158 CDCl3 300MHz 1.02-1.97(14H,m),2.20(1H,m),2.29(2H,t,J=7.2Hz),3.06(1H,m),5.19-5.24 (2H, m),5.58(1H,d,J=6.6Hz),7.62(1H,m),7.72(1H,m),7.86- 7.91 (2H,m),7.96(1H,d,J =7.8Hz),8.04(1H,d.d,J=1.5and8.1Hz),8.34(1H,d,J=1.2Hz). IR(CHCl3)3490,3260,3020,2950,2870,1707,1456,1399,1312,1165/cm. [α]D=-8.3°(CHCl3,C=1.00,23℃). No.1a-159 CDCl3 300MHz 0.92-1.88(14H,m),2.13(1H,m),2.24(2H,m),3.02(1H,m),3.90(3H,s),5.12-5.26(3 H,m),7.29-7.58(4H,m),7.97(1H,d.d,J=1.8and7.5Hz),8.13(1H,d,J=7.5Hz),8.64 (1H,d,J=1.8Hz). IR(CHCl3)3382,3266,3018,2956,1708,1629,1594,1476,1467,1325,1245,1227, 1158,1146/cm. [α]D=+14.6°(CHCl3,C=1.00,22℃). No.1a-160 CDCl3 300MHz 0.93-1.88(14H,m),2.18-2.24(3H,m),3.00(1H,m),5.08-5.2 1(3H,m),7.28-7.33(1 H,m),7.47-7.51(3H,m),7.90(1H,d.d,J=1.5and7.8Hz),8.10(1H,d,J=7.8Hz),8.63 -8.64(2H,m). IR(CHCl3)3465,3380,3275,3020,2957,2876,1708,1627,1604,1495,1473,1457,1328,1240,1222,1156,1149/cm.[α]D=+8.2°(CHCl3,C=1.01,22℃).No.1a-161CDCl3 300MHz0.98-1.88(14H,m),2.17(1H,m),2.24(2H,t,J=7.2Hz),3.05(1H,m),5.16-5.20(2H,m),5.35(1H,d,J=6.6Hz),7.40(1H,m),7.55(1H,m),7.63(1H,d,J=8.1Hz),7.89(1H,d. d,J=1.5and8.1Hz),8.01(1H,m),8.06(1H,d,J=8.1Hz),8.12(1H,d,J=1.5Hz).IR(CHCl3)3478,3266,3028,2952,2874,1708,1454,1417,1323,1196,1148/cm.[α]D=+21.9°(CHCl3,C=1.01,23℃).No.1a-162CDCl3 300MHz0.96-1.98(14H,m),2.02(1H,m),2.25(2H,t,J=7.2Hz),3.05(1H,m),4.10(3H,s),5.14-5.25(2H,m),5.41(1H,d,J=7.2Hz),7.35-7.42(1H,m),7.51-7.64(3H,m),7.94-8.00(1H,m),8.16(1H,s).IR(CHCl3)3368,3274,3028,2952,2874,1708,1633,1583,1465,1452,1438,1413,1315,1151,1103,1053,1024/cm.[α]D=+15.1°(CHCl3,C=1.01,23℃). mp.108-110℃No.1a-163d6-DMSO 300MHz0.97-1.84(14H,m),1.92(1H,m),2.04(2H,t,J=7.5Hz),2.90(1H,m),5.08-5.23 (2H,m),7.32(1H,s),7.38-7.61(2H,m),7.62(1H,s)7.68-7.71(1H,m),7.92(1H,s),8.14-8.17(1H,m),10.7(1H,s),11.9(1H,s).IR(KBr)3350,3295,2952,2874,1707,1636,1601,1466,1431,1389,1315,1251,1174,1146,1106/cm.[α]D=-25.3°(CH3OH,C=1.01,25℃). mp.159-162℃No.1a-164CDCl3 300MHz0.98-1.96(17H,m),2.05(1H,m),2.25(2H,t,J=7.2Hz),3.07(1H,m),4.32(2H,q,J=7.2Hz),5.19-5.23(2H,m),5.31(1H,d,J=7.8Hz),7.38(1H,m),7.41-7.62(3H,m),7.95(1H,m),8.15(1H,s).IR(CHCl3)3360,3018,2946,2870,1709,1633,1457,1445,1425,1394,1314,1176,1152,1105/cm.[α]D=+12.7°(CHCl3,C=1.02,25℃). mp.108-109℃No.1a-165CDCl3 300MHz0.95-1.98(15H,m),2.26(2H,t,J=7.5Hz),3.04(1H,m),4.15 (3H,s),5.20-5.26(2H,m),5.34(1H,d,J=6.9Hz),7.41-7.47(1H,m),7.65-7.68(2H,m),7.89-7.92(1H,m),8.32(1H,s).IR(CHCl3)3366,3087,3022,2957,1708,1632,1538,1463,1408,1364,1346,1308,1227,1212,1205,1167/cm.[α]D=+19.6°(CHCl3,C=1.01,25℃).No.1a-166CDCl3 300MHz0.97-2.02(15H,m),2.27(2H,t,J=6.9Hz),3.07(1H,m),4.14(3H,3),5.21-5.27(2H,m),5.47(1H,d,J=6.9Hz),7.64(1H,s),7.72(1H,d.d,J=0.6和9.0Hz),8.25(1H,s),8.47(1H,d.d,J=2.4and9.0Hz),8.94(1H,d.d,J=0.6和2.4Hz).IR(CHCl3)3373,2957,1708,1639,1587,1528,1467,1428,1415,1345,1221,1184,1155/cm.[α]D=+14.4°(CHCl3,C=0.50,25℃)No.1a-167 CDCl3 300MHz0.92-2.00(14H,m),2.15(1H,m),2.27(2H,t,J=7.2Hz),3.04 (1H,m),3.97(2H,s),5.15-5.30(3H,m),7.35-7.47(2H,m),7.55-7.63(1H,m),7.80-7.96(3H,m),8.05(1H,d,J=0,3Hz).IR(CHCl3)3260,3020,2948,2868,1707,1451,1413,1319,1172,1144,1101,1071/cm.[α]D=+18.2°(CHCl3,C=1.04,22℃).No.1a-168CDCl3 300MHz0.90-1.85(14H,m),2.16(1H,m),2.25(2H,t,J=6.9Hz),3.00(1H,m),5.00-5.19(2H,m),5.35(1H,d,J=6.6Hz),7.25-7.30(1H,m),7.48-7.50(2H,m),7.73(1H,d.d,J=1.5and8.1Hz),8.08-8.14(3H,m),8.93(1H,s).IR(CHCl3)3466,3380,3276,3016,2957,1708,1630,1495,1458,1324,1241,1150/cm.[α]D=+18.0°(CHCl3,C=1.00,22℃).No.1a-169CDCl3 300MHz0.87-1.86(14H,m),2.15(1H,m),2.25(2H,t,J=6.9Hz),2.98(1H,m),3.89(3H,s),5.00-5.22(2H,m),5.27(1H,d,J=6.9Hz),6.88(1H,d.d,J=2.1和8.4Hz),6.94(1H,d,J=2.1Hz),7.69(1H,d.d,J=1.5和7.8Hz),7.92-8.01(3H,m),8.83(1H,s).IR(CHCl3)3465,3378,3276,3022,2957,1708,1630,1609,1569,1459,1433,1314,1281,1229,1151/cm.[α]D=+19.3°(CHCl3,C=1.01,21℃).No.1a-170CDCl3 300MHz0.88-2.25(17H,m),3.04(1H,m),3.84(3H,s),3.95(3H,s),5.06-5.26(3H,m),6.87-6.93(2H,m),7.69(1H,d.d,J=1.6和8.2Hz),7.93-9.05(3H,m).IR(CHCl3)3026,2957,1708,1630,1601,1460,1331,1243,1224,1152/cm.[α]D=+17.2°(CHCl3,C=1.00,22℃).No.1a-171CDCl3 300MHz0.95-2.00(14H,m),2.16-2.32(3H,m),2.66(3H,s),3.14(1H,m),3.68(3H,s),5.09(1H,d,J=6.8Hz),5.10-5.28(2H,m),7.45(1H,d.d.,J=1.8&8.6Hz),7.75-7.84(2H,m).IR(CHCl3)3374,3018,2946,2868,1725,1585,1513,1436,1340,1278,1153,1112/cm.[α]D=-14.7°(CHCl3,C=1.07,25.0℃).No.1a-172CDCl3 300MHz0.97-2.02(14H,m),2.23(1H,m),2.28(2H,t,J=7.2Hz),2.66(3H,s),3.14(1H,m),5.12-5.22(2H,m),5.41(1H,d,J=7.2Hz),7.45(1H,d.d.,J=2.1&8.7Hz),7.76(1H,d,J=8.7Hz),7.78(1H,d,J=2.1Hz).IR(CHCl3)3372,3250,3022,2950,2868,1707,1514,1419,1336,1279,1154,1112/cm.[α]D=-4.1°(CHCl3,C=1.08,26.0℃) m.p.141-143℃No.1a-173CDCl3 300MHz1.15-2.42(17H,m),2.91(1H,m),5.15(1H,d,J=4.2Hz),5.25-5.40(2H,m),7.85(1H,t,J=7.2Hz),8.00(1H,t,J=8.1Hz),8.15-8.20(2H,m),8.67(1H,d,J=8.1Hz),8.73(1H,d,J=8.1Hz),8.83(1H,s),9.43(1H,s).IR(KBr)3422,3269,3046,2952,2871,1711,1617,1447,1333,1243,1161,1146/cm.[α]D=-41.0°(CH3OH,C=1.01,23℃).No.1a-174CDCl3+d6-DMSO 300MHz1.00-1.92(14H,m),2.20(2H,t,J=6.6Hz),2.35(1H,m),2.92(1H,m),5.05-5.22(2H,m),6.63(1H,d,J=5.4Hz),7.77-7.92(3H,m),8.31(1H,d.d,J=1.8和8.7Hz),8.59(1H,d,J=8.7Hz),8.73(1H,d,J=8.7Hz),9.01(1H,s),9.55(1H,d,J=1.8Hz).IR(KBr)3433,3252,2952,2871,1696,1578,1423,1335,1308,1219,1185,1160,1106/cm.[α]D=-19.3°(DMSO,C=0.50,23℃).No.1a-175CDCl3 300MHz0.96-1.87(14H,m),2.20-2.25 (3H,m),2.95(1H,m),3.66 (3H,s),4.74(1H,d,J=6.6Hz),5.10-5.12(2H,m),6.88(1H,d,J=1.2Hz),7.37-7.50(3H,m),7.56(1H,dd,J=8.7,1.5Hz),7.68-7.77(3H,m),8.06(1H,s),9.44(1H,dd,J=1.2Hz).IR(CHCl3)3462,3374,3026,3006,2952,2872,1724,1610,1580,1484,1452,1358,1309,1147.[α]D=+16.4°(CHCl3,C=1.05,26℃). mp.130-132℃.No.1a-176CDCl3+CD3OD 300MHz 1.00-2.02(14H,m),2.22(1H,m),2.29(2H,t,J=6.9Hz),2.88 (1H,m),5.16-5.26(2H,m),6.87(1H,s),7.28-7.57(4H,m),7.69(1H,d,J=8.4Hz),7.75-7.78(2H,m),7.99(1H,s).IR(KBr)3254,2944,1704,1484,1453,1358,1305,1147.[α]D=+13.0°(CH3OH,C=1.02,24℃),mp.160-161℃No.1a-177CDCl3 300MHz0.96-1.88(14H,m),1.88-2.26(3H,m),2.94(1H,m),3.67(3H,s),3.87(3H,s),4.67(1H,brs),5.08-5.14(2H,m),6.77(1H,d,J=1.5Hz),6.99-7.02(2H,m),7.53-7.57(1H,m),7.65-7.70(3H,m),8.00(1H,s),9.27(1H,brs).IR(CHCl3)3426,3376,3006,2952,1724,1610,1495,1438,1357,1308,1282,1249,1177,1147/cm.[α]D=+18.1°(CHCl3,C=1.02,22℃).No.1a-178CDCl3+CD3OD 300MHz0.96-1.91(14H,m),2.19(1H,m),2.27(2H,t,J=6.0Hz),2.85(1H,m),3.87(3H,s),5.16-5.23(2H,m),6.99-7.02(2H,m),7.41(1H,m),7.64-7.73(3H,m),7.92(1H,m).IR(CHCl3)3366,3261,3004,2954,2873,1705,1611,1496,1458,1438,1304,1286,1253,1180,1149,1128/cm.[α]D=+14.6°(CHCl3,C=1.02,22℃).No.1a-179CDCl3+CD3OD300MHz0.96-1.87(14H,m),2.15-2.23(3H,m),2.93(1H,m),3.85(3H,s),5.10-5.16(2H,m),6.90-6.93(2H,m),7.50(1H,m),7.60-7.65(3H,m),7.91(1H,d,J=0.9Hz).IR(CHCl3)3369,3270,2950,2873,1719,1612,1498,1456,1440,1359,1306,1269,1219,1146,1127/cm.[α]D=+18.1°(CH3OH,C=1.00,22℃).No.1a-180CDCl3+CD3OD300MHz1.03-1.86(14H,m),2.08-2.17(3H,m),2.91(1H,m),5.06-5.10(2H,m),6.76(1H,m),6.86-6.90(2H,m),7.48(1H,m),7.61-7.69(3H,m),7.89(1H,m).IR(CHCl3)3360,3259,2954,2873,1706,1612,1497,1457,1360,1306,1272,1230,1176,1148,1126/cm.[α]D=+20.3°(CH3OH,C=1.00,22℃).No.1a-181CDCl3 300MHz0.97-1.96(14H,m),2.15(1H,m),2.29(2H,t,J=6.9Hz),3.05(1H,m),3.81(3H,s),5.08(1H,d,J=6.9Hz),5.23-5.25(2H,m),6.62(1H,s),7.47-7.54(5H,m),7.59(1H,m),7.70(1H,m),7.97(1H,m).IR(CHCl3)3380,3260,3020,2946,2868,1708,1466,1388,1328,1149/cm.[α]D=+32.9°(CHCl3,C=1.07,22℃).No.1a-182CDCl3 300MHz0.94-1.90(14H,m),2.25(2H,t,J=7.5Hz),2.30(1H,m),2.98(1H,m),3.70(3H,s),4.83(1H,d,J=6.6Hz),5.13-5.16(2H,m),6.95(1H,d,J=1.5Hz),7.11-7.23(2H,m),7.43(1H,d,J=8.1Hz),7.65(1H,d,J=8.1Hz),7.79-7.93(4H,m),9.08(1H,br).IR(CHCl3)3458,3372,3020,3002,2946,2868,1719,1598,1452,1422,1321,1300,1157/cm.[α]D=-6.6°(CHCl3,C=1.00),mp150-151℃No.1a-183CDCl3 300MHz0.95-1.94(14H,m),2.26(1H,m),2.28(2H,t,J=7.5Hz),3.00(1H,m),5.16-5.19(2H,m),5.32(1H,d,J=7.2Hz),6.93(1H,d,J=1.2Hz),7.13(1H,m),7.22(1H,dd,J=7.8,6.6Hz),7.42(1H,d,J=7.8Hz),7.63(1H,d,J=7.8Hz),7.76 (2H,d,J=8.4Hz),7.90(2H,d,J=8.4Hz),8.95(1H,br).IR(CHCl3)3458,3374,3260,3020,3002,2948,2868,1708,1598,1452,1422,1301,1156/cm.[α]D=+17.9°(CHCl3,C=1.01,22℃).No.1a-184CDCl3 200MHz0.92-2.00(14H,m),2.20(1H,m),2.34(2H,t,J=6.8Hz),3.05(1H,m),5.20-5.36(3H,m),7.39 -7.44(2H,m),7.61-7.66(1H,m),7.80-7.84(1H,m),8.05(2H,d,J=8.6Hz),8.40(2H,d,J=8.6Hz).IR(CHCl3)3384,3271,3019,2958,1709,1615,1599,1551,1453,1405,1344,1326,1243,1163/cm.[α]D=+18.5°(CHCl3,C=1.00,21℃).No.1a-185CDCl3 300MHz0.89-2.20(15H,m ),2.26(2H,d.t,J=2.1and7.2Hz),2.99(1H,m),5.08(1H,d,J=6.3Hz),5.09-5.24(2H,m),6.90(1H,d,J=1.2Hz),7.32-7.48(4H,m),7.64-7.72(3H,m),8.20(1H,d,J=1.2Hz),9.00(1H,s).IR(CHCl3)3464,3375,3275,3022,2956,1707,1605,1490,1449, 1356,1322,1219,1147,1131/cm.[α]D=+21.6°(CHCl3,C=1.01,23℃).No.1a-186CDCl3300MHz1.36-2.24(14H,m),2.31(2H,t,J=7.4Hz),2.49(1H,brs),3.37(1H,m),3.67(3H,s),5.38-5.50(2H,m),7.40-7.68(9H,m).IR(CHCl3)3375,1727,1602,1435,1362,1221,1207,1168,1045/cm.No.1a-187CDCl3300MHz1.10-2.25(14H,m),2.36(2H,t,J=7.2Hz),2.47(1H,m),3.37(1H,m),5.35-5.54(2H,m),5.62(1H,d,J=7.2Hz),7.39-7.70(9H,m).IR(CHCl3)3674,3496,3376,3234,3012,2952,2880,2650,1725(sh),1709,1602,1485,1420,1360,1167/cm.[α]D=+32°(CHCl3,C=1.69).No.1a-188CDCl3 200MHz0.86-1.92(14H,m),2.22(3H,m),2.36(3H,s),2.95(1H,m),3.67(3H,s),3.93(3H,s),4.81(1H,d,J=6.2Hz),5.04-5.20(2H,m),7.02-7.05(2H,m),7.31(1H,d,J=8.6Hz),7.39(1H,d,J=7.8Hz),7.79-7.89(3H,m).IR(CHCl3)3385,3286,3029,3019,3015,2954,2877,1718,1617,1598,1567,1507,1311,1269,1153/cm.[α]D=-29.4°(CHCl3,C=1.01,25℃).No.1a-189[α]D=-7.7°(CHCl3,C=1.00,24℃).No.1a-190[α]D=-17.3°(CHCl3,C=1.00,24℃).No.1a-191CDCl3 300MHz0.95-2.20(14H,m),2.30(1H,m),2.36(2H,d,J=6.9Hz),3.21(1H,m),4.25(2H,s),5.07(1H,d,J=7.8Hz),5.35-5.48(2H,m),7.25(1H,dd,J=1.8和8.1Hz),7.32-7.35(2H,m),7.59(1H,d,J=8.1Hz),7.94(1H,s),8.14(1H,d,J=2.7Hz),8.23(1H,d.d,J=2.7and8.7Hz).IR(CHCl3)3386,3026,3015,2957,2877,2633,1702,1617,1573,1530,1348,1123/cm.[α]D=-6.1°(CHCl3,C=1.01,25℃).No.1a-192CDCl3 300MHz0.92-2.20(14H,m),2.13(3H,m),3.23(1H,m),3.64(3H,s),3.94(3H,s),4.22(2H,s),4.36(1H,d,J=7.8Hz),5.37-5.42(2H,m),7.16-7.42(6H,m),7.53(1H,d,J=8.4Hz),7.94(1H,s).IR(CHCl3)3389,3022,3013,2953,2877,1716,1616,1560,1485,1340,1326,1124/cm.[α]D=-15.2°(CHCl3,C=1.01,25℃).No.1a-193CDCl3 300MHz0.92-2.20(14H,m),2.25(1H,m),2.35(2H,t,J=7.2Hz),3.17(1H,m),4.22(2H,s),4.91(1H,d,J=7.5Hz),5.37-5.42(2H,m),7.13-7.43(6H,m),7.60(1H,d,J=8.1Hz),8.05(1H,s).IR(CHCl3)3511,3387,3029,3020,3011,2957,2877,2651,1698,1614,1560,1505,1320,1280,1252,1126/cm.[α]D=-0.9°(CHCl3,C=1.00,25℃).No.1b-1CDCl3 300MHz0.98-1.56(15H,m),1.85-1.90(5H,m),2.23(1H,m),3.05 (1H,m),3.66(3H,s),4.77(1H,d,J=6.0Hz),5.08-5.28(2H,m),7.46(3H,m),7.38-7.54(2H,d,J=7.5Hz),7.72(2H,d,J=8.4Hz),7.93(2H,d,J=8.4Hz).IR(CHCl3)3384,3028,2952,2876,1719,1595,1391,1322,1155/cm.[α]436 +4.0~+6.0(CHCl3,C=1.00,23℃).mp.96-98℃No.1b-2CDCl3 300MHz0.98-1.52(15H,m),1.85-1.90(5H,m),2.17(1H,m),3.00(1H,m),3.67(3H,s),4.05(2H,s),4.83(1H,d,J=6.0Hz),5.05-5.23(2H,m),7.14(2H,d,J=7.2Hz),7.17-7.32(5H,m),7.78(2H,d,J=8.4Hz).IR(CHCl3)3384,3026,2952,2874,1719,1595,1453,1407,1320,1180/cm.[α]D=+2.5°(CHCl3,C=1.02,24℃).No.1b-3CDCl3 300MHz0.96-2.05(20H,m),2.07(1H,m),3.07(1H,m),4.04(2H,s),5.21-5.35(2H,m),5.55(1H,d,J=6.9Hz),7.14(2H,d,J=6.6Hz),7.20-7.32(5H,m),7.78(2H,d,J=8.1H).IR(CHCl3)3250,3022,2950,1699,1596,1495,1453,1405,1318,1153/cm.[α]D=+17.1°(CHCl3,C=1.01,25℃).mp.129-131℃.No.1b-4CDCl3 200MHz0.90-2.10(15H,m),1.19(3H,s),1.20(3H,s),3.11(1H,m),5.24-5.32(2H,m),5.70(1H,d,J=6.6Hz),7.38-7.68(4H,m),7.96-8.04(2H,m),8.53(1H,d,J= 1.4Hz).IR(CHCl3)3384,3246,2958,1701,1632,1595,1468,1445,1322,1216,1202,1190,1155,1122/cm.[α]D=+10.8°(CHCl3,C=0.51,23℃).No.1b-51.02-2.10(15H,m),1.16(6H,s),3.02(1H,m),4.09(3H,s),5.23-5.28(2H,m),5.76(1H,d,J=7.2Hz),7.36-7.63(4H,m),7.97(1H,d,J=7.8Hz),8.16(1H,s).IR(CHCl3)3369,2959,1702,1635,1585,1468,1454,1441,1415,1318,1222,1189,1170,1154/cm.[α]D=+9.9°(CHCl3,C=1.00,23℃).No.1c-1CDCl3 300MHz1.10-2.02(14H,m),2.27(2H,t,J=7.5Hz),2.50(1H,m),2.89(3H,s),3.31(1H,m),3.64(3H,s),5.16-5.30(2H,m),7.34-7.42(3H,m),7.50-7.59(2H,m),7.62-7.68(2H,m),7.76-7.82(2H,m).IR(CHCl3)3020,2946,2868,2212,1727,1596,1495,1437,1339,1156,1135,1084/cm.[α]D=-16.1°(CHCl3,C=1.05,25.0℃).m.p. 100-102℃No.1c-2CDCl3 300MHz1.10-2.05(14H,m),2.23(2H,t,J=7.5Hz),2.53(1H,m),2.91(3H,s),3.35(1H,m),3.62(3H,s),5.02-5.30(2H,m),7.50-7.60(3H,m),7.90-8.08(6H,m).IR(CHCl3)3016,2946,2868,1728,1437,1398,1340,1160,1086/cm.[α]D=-32.5°(CHCl3,C=1.00,25.0℃).No.1c-3CD3OD 300MHz1.15-2.05(14H,m),2.13(2H,t,J=7.2Hz),2.47(1H,m),2.91(3H,s),3.27(1H,m),4.90-5.30(2H,m),7.37-7.44(3H,m),7.53-7.61(2H,m),7.71-7.77(2H,m),7.81-7.87(2H,m).IR(KBr)3412,2999,2951,2871,2217,1560,1399,1243,1159,1137,1103,1084.[α]D=-8.6°(CH3OH,C=1.03,23℃).No.1d-1CDCl3 300MHz1.00-2.16(15H,m),2.36(2H,t,J=7.2Hz),3.17(1H,m),3.33(3H,s),5.23-5.43(3H,m),7.51-7.59(3H,m),7.91-8.10(6H,m),9.02(1H,brs).IR(CHCl3)3382,3268,3028,2954,2874,1715,1442,1400,1337,1162,1120,1089/cm.[α]D=+40.0°(CHCl3,C=0.53,22℃).No.1d-2CDCl3 300MHz1.03-2.30(17H,m),3.03(1H,m),4.03(2H,s),5.26(2H,m),5.84(1H,br),5.25-5.29(1H,d,J=6.6Hz),6.03(1H,br),7.14(2H,d,J=8.1Hz),7.26-7.31(5H,m),7.80(2H,d,J=8.1Hz).IR(CHCl3)3376,3002,2946,1669,1595,1492,1454,1406,1318,1154/cm.[α]D=+4.3°(CHCl3,C=1.00,23℃).No.1d-3CDCl3 300MHz0.96-2.17(17H,m),2.33(2H,t,J=6.9Hz),3.01(1H,m),4.04(2H,s),5.10(1H,d,J=6.6Hz),5.21-5.26(2H,m),7.14(2H,d,J=8.7Hz),7.16-7.32(5H,m),7.78(2H,d,J=8.4Hz).IR(CHCl3)3260,3020,2946,1711,1596,1492,1457,1407,1318,1154/cm.[α]D=+9.3°(CHCl3,C=1.09,25℃).No.1d-4CDCl3 300MHz0.95-2.14(15H,m),2.34(2H,t,J=7.2Hz),3.09(1H,m),3.30(3H,s),4.04(2H,s),5.19(1H,d,J=7.2Hz),5.22-5.39(2H,m),7.10-7.35(7H,m),7.8 1(2H,d,J=8.1Hz),9.10(1H,brs).IR(CHCl3)3382,3260,3028,2952,2874,2670,1713,1595,1492,1450,1405,1338,1160,1120,1092/cm.[α]D=+22.2°(CHCl3,C=1.07,22℃).No.1d-5CDCl3 300MHz1.00-2.10(14H,m),2.30-2.39(3H,m),3.15(1H,m),3.35(3H,s),5.18-5.40(3H,m),7.41(1H,d.t.,J=0.9and7.8Hz),7.50-7.69(3H,m),7.88-8.15(2H,m),8.60(1H,d,J=1.5Hz),9.06(1H,s).IR(CHCl3)3382,3268,3028,2954,2874,1714,1442,1402,1338,1188,1155,1121,1072/cm.[α]D=+15.3°(CHCl3,C=1.00,22℃).No.1e-1CDCl3 300MHz1.19-2.45(19H,m),2.58(1H,m),5.63(1H,d,J=3.0Hz),7.42- 7.65(4H,m),7.94-8.03(2H,m),8.49-8.50(1H,m).IR(CHCl3)3293,3024,1710,1595,1584,1467,1445,1410,1324,1222,1213,1206,1190,1160/cm.[α]D=-41.1°(CHCl3,C=1.01,23℃).No.1e-2CDCl3 300MHz1.10-2.25(19H,m),2.94(1H,m),4.12(3H,s),5.53(1H,d,J=7.2Hz),7.39(1H,m),7.50-7.62(3H,m),7.96(1H,d,J=7.5Hz),8.13(1H,s).IR(CHCl3)3367,3025,2955,1711,1634,1600,1584,1468,1454,1440,1415,1342,1317,1222,1189,1157/cm.[α]D=+1.2°(CHCl3,C=1.00,25℃).No.1f-1CDCl3 300MHz1.08-2.47(19H,m),2.56(1H,m),3.52(2H,t,J=6.6Hz),5.59(1H,d,J=2.4Hz),7.40-7.66(4H,m),7.95-8.04(2H,m),8.50(1H,d,J=1.8Hz).IR(CHCl3)3624,3383,3295,2950,2877,1705,1595,1584,1468,1445,1405,1347,1337,1324,1224,1190,1160/cm.[α]D=-54.1°(CHCl3,C=1.01,23℃).No.1f-2CDCl3 300MHz1.08-2.24(19H,m),2.94(1H,m),3.53(2H,t,J=6.3Hz),4.13(3H,s),5.47(1H,d,J=6.6Hz),7.36-7.63(4H,m),7.96(1H,d,J=6.3Hz),8.14(1H,s).IR(CHCl3)3625,3368,3025,3013,2949,2877,1710,1634,1600,1584,1468,1454,1440,1415,1342,1317,1232,1220,1189,1157/cm.[α]D=-5.6°(CHCl3,C=1.00,25℃).No.1g-1CDCl3 200MHz1.17-2.34(15H,m),3.22(1H,m),5.10-5.16(2H,m),5.45(1H,d,J=7.0Hz),7.35-7.66(4H,m),7.95-8.01(2H,m),8.51(1H,d,J=2.0Hz).IR(CHCl3)3383,3275,2959,1707,1595,1584,1468,1445,1425,1319,1269,1248,1190,1149,1123/cm.[α]D=+64.3°(CHCl3,C=1.01,23℃).No.1g-2CDCl3 300MHz1.10-2.15(13H,m),2.36(2H,t,J=7.2Hz),3.21(1H,m),4.09(3H,s),5.10-5.22(2H,m),5.43(1H,d,J=7.8Hz),7.36-7.62(4H,m),7.96(1H,d,J=7.8Hz),8.12(1H,s).IR(CHCl3)3366,2959,1708,1635,1600,1585,1467,1454,1440,1415,1345,1318,1233,1189,1152/cm. [α]D=+103.1°(CHCl3,C=1.01,23℃).No.1h-1CDCl3 300MHz0.90-1.60(17H,m),1.83(1H,m),2.11(1H,m),2.22(2H,t,J=7.2Hz),3.07(1H,m),5.11(1H,d,J=7.2Hz),7.38-7.47(1H,m),7.50-7.60(1H,m),7.60-7.72(2H,m),7.88-8.12(2H,m),8.54 (1H,d,J=0.9Hz).IR(CHCl3)3382,3274,2926,1707,1464,1442,1318,1266,1188,1153,1121,1105,1071,1019/cm.[α]D=-2.8°(CHCl3,C=1.01,23℃).No.1i-1[α]365+50.9°(CHCl3,C=1.01,24℃).No.1i-2CDCl3 300MHz0.98-1.70(11H,m),1.80-2.00(5H,m),2.19(1H,m),3.03(1H,m),3.64(2H,t,J=6.6Hz),4.05(2H,s),4.69(1H,d,J=6.6Hz),5.15(1H,m),5.25(1H,m),7.16(2H,d,J=7.2Hz),7.27-7.32(5H,m),7.77(2H,d,J=8.4Hz).IR(CHCl3)3376,3004,2946,2316,1596,1492,1453,1407,1318,1154/cm.[α]D=+3.5°(CHCl3,C=1.00,22℃).mp.80.5-82.0℃No.1j-1[α]436=-7.5±0.5°(CHCl3,C=1.05,22℃).No.1j-2[α]D=-9.7±0.5°(CHCl3,C=1.06,22℃).No.1j-3[α]D=+15.0±0.5°(CH3OH,C=1.06,24.5℃).mp.101-108℃No.1j-4[α]D=-28.0±0.6°(CHCl3,C=1.06,24℃).mp.159-161℃1j-5[α]D=-12.5±0.5°(CHCl3,C=1.04,23℃).mp.99-101℃No.1j-6CDCl3 300MHz0.90-2.03(14H,m),2.20(1H,m),2.30(2H,t,J=7.3Hz),3.00(1H,m)3.68(3H,s),4.76(1H,d,J=6.8Hz),5.13-5.35(2H,m),7.01-7.08(4H,m),7.19-7.26(1H,m),7.37-7.46(2H,m),7.80-7.84(2H,m).IR(CHCl3)3382,3280,3080,3016,2952,2900,1727,1582,1486,1432,1322,1150/cm.[α]D=-31.0°(CHCl3,C=1.05,26℃).No.1j-7CDCl3 300MHz0.91-2.09(14H,m),2.15(1H,m),2.35(2H,t,J=7.5Hz),3.01(1H,m),5.17(1H,d,J=6.8Hz),5.21-5.34(2H,m),7.01-7.08(4H,m),7.15-7.27(1H,m),7.37-7.43(2H,m),7.80-7.85(2H,m).IR(CHCl3)3474,3386,3270,3024,2958,2900,2675,1711,1584,1488,1420,1323,1298,1150/cm.[α]D=-13.4°(CHCl3,C=1.01,26℃).No.1j-8CDCl3 300MHz0.95-2.14(13H,m),2.30(2H,t,J=7.5Hz),2.36(1H,m),2.84(1H,m),2.91(1J=4.8Hz),3.66 (3H,s),5.33-5.52(2H,m),6.82-6.87(1H,m),6.93-7.00(2H,m),7.09-7.15(4H,m),7.28-7.36 (2H,m),7.54-7.59(1H,m).IR(CHCl3)3350,3010,2950,2880,1728,1603,1582,1489 1461,1438,1360,1160/cm.[α]D=+75.1°(CHCl3,C=1.13,26℃).No.1j-9CDCl3 300MHz0.95-2.03(14H,m),2.20(1H,m),2.29(2H,t,J=7.5Hz),3.06(1H,m),3.68(3H,s),4.98(1H,d,J=7.4Hz),5.14-5.34(2H,m),7.46-7.54(2H,m),7.60-7.68(1H,m),7.75-7.80(2H,m),7.88-7.92(2H,m),7.99-8.03(2H,m).IR(CHCl3)3384,3280,3020,2960,2888,1727,1662,1600,1316,1273,1163/cm.[α]D=-41.0°(CHCl3,C=1.17,26℃).No.1j-10CDCl3+CD3OD 300MHz0.94-2.08(14H,m),2.21(1H,m),2.34(2H,t,J=6.2Hz),3.04(1H,m),5.21-5.35(2H,m),5.40(1H,m),7.49-7.58(2H,m),7.64-7.68(1H,m),7.79-8.06(6H,m).IR(CHCl3)3475,3370,3250,3018,2956,2976,2650,1709,1662,1595,1445,1420,1395,1317,1274,1163/cm.[α]D=-17.1°(CHCl3,C=1.13,25℃).No.1j-11CDCl3 300MHz1.06-1.98(14H,m),2.24-2.29(3H,m),3.13(1H,m),3.66(3H,s),5.10-5.24(2H,m),5.40(1H,d,J=6.3Hz),7.39-7.49(3H,m),7.59-7.64(3H,m),7.80-7.83(2H,m),8.08-8.11(1H,m).IR(CHCl3)3302,3012,2948,2905,1727,1661,1593,1435,1332,1312,1287,1271,1165/cm.[α]D=+15.6°(CHCl3,C=1.03,26℃).No.1j-12 CDCl3 300MHz 1.08-1.98(14H,m),2.23(1H,m),2.33(2H,t,J=7.5Hz),3.16(1H,m),5.18-5.26(2H,m),5.39-5.45(1H,m),7.39-7.49(3H,m),7.60-7.64(3H,m),7.80-7.83(2H,m),8.09-8.12(1H,m).IR(CHCl3)3325,3022,2956,2872,2680,1708,1662,1603,1598,1425,1340,1316,1288,1271,1165/cm.[α]D=+9.7°(CHCl3,C=0.52,25℃).No.1j-13CDCl3 300MHz0.95-2.00(14H,m),2.20(1H,m),2.27(2H,t,J=6.3Hz),3.03(1H,m),3.67(3H,s),4.99(1H,d,J=6.6Hz),5.12-5.31(2H,m),7.47-7.55(2H,m),7.60-7.69(2H,m),7.76-7.81(2H,m),7.96-8.05(1H,m),8.08-8.14(1H,m),8.27-8.28(1H,m).IR(CHCl3)3674,3538,3376,3276,3012,2948,2860, 1726,1662,1595,1440,1335,1317,1297,1274,1166,1150/cm.[α]D=+10.2°(CHCl3,C=1.00,25℃).No.1j-14CDCl3 300MHz0.93-2.08(14H,m),2.21(1H,m),2.32(2H,t,J=6.3Hz),3.00(1H,m),5.20-5.36(2H,m),5.38(1H,d,J=6.2Hz),7.50-7.55(2H,m),7.63-7.71(2H,m),7.77-7.81(2H,m),7.99-8.04(1H,m),8.10-8.18(1H,m),8.32-8.36(1H,m).IR(CHCl3)3674,3480,3374,3258,3012,2950,2875,2650,1709,1662,1598,1418,1335,1317,1274,1143/cm.[α]D=+61.0°(CHCl3,C=1.19,25℃).No.1j-15CDCl3 300MHz0.90-2.00(14H,m),2.19(1H,m),2.30(2H,t,J=7.3Hz),3.01(1H,m),3.67(3H,s),4.82(1H,d,J=6.6Hz),5.14-5.34(2H,m),7.36-7.39(3H,m), 7.53-7.57(2H,m),7.62-7.66(2H,m),7.83-7.88(2H,m).IR(CHCl3)3376,3276,3010,2948,2868,2212,1727,1597,1500,1437,1325,1161/cm.[α]D=-7.2°(CHCl3,C=1.00,26℃).No.1j-16CDCl3 300MHz0.93-2.03(14H,m),2.15(1H,m),2.36(2H,t,J=7.5Hz),3.05(1H,m),5.20-5.40(3H,m),7.36-7.39(3H,m),7.55-7.66(4H,m),7.84-7.88(2H,m).IR(CHCl3)3470,3376,3260,3012,2950,2868,2675,2212,1708,1596,1503,1416,1396,1322,1160.[α]D=-22.4°(CHCl3,C=1.00,26℃).No.1j-17CDCl3 300MHz1.00-1.60(9H,m),1.79-1.89(5H,m),2.17(1H,brs),2.23(2H,t,J=7.2Hz),3.03(1H,m),5.10-5.23(2H,m),5.49(1H,d,J=6.6Hz),7.40(1H,t,J=7.4Hz),7.53(1H,t,J=7.2Hz),7.60-7.68(2H,m),7.98-8.03(2H,m),8.55(1H,d,J=1.5Hz).IR(CHCl3)3516,3384,3270,2666,1708,1632,1595,1584,1467,1445,1425,1374,1345,1321,1269,1248,1218/cm.[α]D=-7.8°(CHCl3,C=1.01,22℃).No.1j-18CDCl3 300MHz0.90-2.03(14H,m),2.19(1H,m),2.30(2H,t,J=7.5Hz),3.00(1H,m),3.67(3H,s),4.80(1H,d,J=6.4Hz),5.14-5.35(2H,m),6.99-7.04(2H,m),7.16-7.22(2H,m),7.34-7.49(4H,m),7.57-7.61(1H,m).IR(CHCl3)3376,3276,3012,2948,2875,1727,1583,1488,1471,1432,1330,1311,1150/cm.[α]D=+54.0°(CHCl3,C=0.99,25℃).No.1j-19CDCl3 300MHz0.91-2.09(14H,m),2.15(1H,m),2.34(2H,t,J=7.5Hz),3.01(1H,m),5.16(1H,d,J=6.6Hz),5.24-5.40(2H,m),7.01-7.08(2H,m),7.15-7.25(2H,m),7.35- 7.53(4H,m),7.59-7.65(1H,m).IR(CHCl3)3470,3376,3260,3012,2950,2875,2640,1708,1583,1488,1471,1430,1335,1305,1149/cm.[α]D=-21.0°(CHCl3,C=1.30,25℃).No.1j-20CDCl3 300MHz1.17(1H,m),1.26-1.34(2H,m),1.54-2.24(11H,m),2.31(2H,t,J=7.4Hz),2.48(1H,brs),3.37(1H,m),3.67(3H,s),5.35-5.50(2H,m),7.39-7.68(9H,m).IR(CHCl3)3377,1727,1601,1435,1362,1168/cm.No.1j-21CDCl3 300MHz1,10-2.25(14H,m),2.36(2H,t,J=7.2Hz),2.47(1H,m),2.89(1H,m),5.35-5.53(2H,m),5.63(1H,d,J=7.2Hz),7.40-7.71(9H,m).IR(CHCl3)3674,3496,3374,3234,3010,2952,2870,2640,1730(sh),1710,1605,1485,1425,1360,1167/cm.[α]D=-43.0°(CHCl3,C=1.01,25℃).No.1j-22CDCl3 300MHz0.98-1.95(14H,m),2.25-2.31(3H,m),2.95(1H,m),5.19-5.30(2H,m),5.33(1H,d,J=3.9Hz),6.58(1H,d,J=7.5Hz),6.80(1H,t,J=7.5Hz),6.99-7.05(1H,m),7.44-7.53(6H,m),7.60-7.73(9H,m),7.94-7.73(3H,m),8.23-8.26(2H,m),10.66(1H,s).IR(CHCl3)3475,3372,3260,3008,2952,2868,2722,1725,1710(sh),1663,1590,1571,1525,1448,1437,1345,1314,1161,1112/cm.[α]D=+12.9°(CHCl3,C=0.12,23℃).No.1j-23CDCl3 300MHz0.94~1.94(14H,m),2.23-2.30(3H,m),2.98(1H,m),3.68(3H,s),5.09 (1H,d,J=6.2Hz),5.15-5.28(2H,m),7.14-7.22(1H,m),7.34-7.42(2H,m),7.68-7.73(2H,m),7.89-8.03(4H,m),8.51(1H,s).IR(CHCl3)3372,3275,1724,1673,1599,1438,1320,1161/cm.[α]D=+17.0°(CHCl3,C=1.38,25℃).No.1j-24CDCl3+CD3OD 300MHz0.96-2.05(14H,m),2,25-2.34(3H,m),2.92(1H,m),5.16- 5.34(2H,m),7.14-7.22(1H,m),7.29-7.42(2H,m),7.70(2H,d,J=7.6Hz),7.92-8.05(4H,m).IR(CHCl3)3616,3426,3375,3010,2950,2828,2645,1708,1672,1599,1439,1323,1161/cm.[α]D=+21.0°(CH3OH,C=1.00,22℃).No.1j-25CDCl3 300MHz1.03(1H,m),1.18-2.01(13H,m),2.20(1H,brs),2.27(2H,t,J=7.4Hz),3.08(1H,m),3.66(3H,s),5.11(1H,d,J=6.6Hz),5.14-5.34(2H,m),7.54- 7.62(3H,m),8.04-8.32(6H,m). IR(CHCl3)3384,3278,1726,1605,1484,1448,1331,1161/cm. No.1j-26 CDCl3+CD3OD 300MHz 1,03-2.10(14H,m),2.22(1H,m).2.31(2H,t,J=7.5Hz),2.98(1H,m),5.23-5.38(2H, m),7.55-7.66(3H,m),8.05-8.08(2H,m),8.14-8.18(2H,m),8.28-8.31(2H,m). IR(Nujol)3260,2720,2660,1711,1545,1460,1317,1163/cm. [α]D=+15.8°(CH3OH,C=1.01,22℃).No.1j-27[α]D=+16.7°(CHCl3,C=1.00,23℃).No.1j-28CDCl3 300MHz1.01(1H,m),1.14-1.29(2H,m),1.46-2.19(11H,m),2.33(2H,t,J=7.2Hz),2.41(1H,brs),3.18-3.21(5H,m),3.68(3H,s),3.73-3.76(4H,m),4.37(1H,d,J=7.2Hz),5.35- 5.45(2H,m).IR(CHCl3)3392,1727,1435,1335,1148/cm.[α]D=+10.7°(CHCl3,C=1.39,26℃).No.1j-29CDCl3 300MHz1.00(1H,m),1.20-1.29(2H,m),1.48-2.25(12H,m),2.37(2H,t,J=7.2Hz),3.17-3.22(5H,m),3.74-3.79(4H,m),4.79(1H,d,J=7.8Hz),5.34-5.54(2H,m).IR(CHCl3)3470,3390,3270,2675,1709,1455,1420,1315,1147/cm.[α]D=+16.8°(CHCl3,C=1.42,26℃).No.1k-1[α]D=-25.4°(CHCl3,C=1.08,23℃).No.1k-2CDCl3 200MHz1.07-2.28(14H,m),2.32(2H,t,J=7.4Hz),2.63(1H,m),3.63(3H,s),3.93(1H,m),5.30-5.52(2H,m),6.35(1H,d,J=7.0Hz),7.48-7.60(3H,m),7.88-8.02(6H,m) .IR(CHCl3)3438,3002,2946,2868,1727,1652,1514,1485,1363,1310,1245,1154/cm.[α]D=-80.4°(CHCl3,C=1.01,24.0℃).No.1k-3CDCl3 200MHz1.10-2.26(14H,m),2.37(2H,t,J=7.2Hz),2.60(1H,m),3.93 (1H,m),5.30-5.50(2H,m),6.33(1H,d,J=7.5Hz),7.48-7.58(3H,m),7.88-7.99(6H,m).IR(CHCl3)3446,3004,2952,2874,1709,1652,1515,1485,1305,1153/cm.[α]D=-96.4°(CHCl3,C=1.05,23.0℃).No.1k-4CDCl3 300MHz1.05-2.17(14H,m),2.38(2H,t,J=7.2Hz),2.52(1H,m),3.8 1(1H,m),5.33-5.50(2H,m),6.08(1H,d,J=7.6Hz),7.39-7.53(3H,m),7.57-7.62(6H,m).IR(CHCl3)3420,3250,3008,2948,2870,2660,2208,1735(sh),1705,1640,1500/cm.[α]D=-21.9±0.6°(CHCl3,C=1.02,22℃).No.1k-5CDCl3 300MHz1.05-2.14(14H,m),2.38(2H,t,J=7.2Hz),2.51(1H,m),3.81(1H,m),5.34-5.46(2H,m),6.07(1H,d,J=7.6Hz),7.33-7.56(5H,m).IR(CHCl3)3422,3250,3010,2950,2876,2664,2558,2210,1735(3h),1705,1645,1502,1441,1410,1307,1276/cm.[α]D=-63.6±1.9°(CHCl3,C=0.56,22℃).No.1k-6CDCl3 300MHz1.04-2.24(14H,m),2.36(2H,t,J=7.5Hz),2.58(1H,m),3.88(1H,m),5.30-5.43(2H,m),6.21(1H,d,J=7.2Hz),7.41-7.49(3H,m),7.73-7.77(2H,m).IR(CHCl3)3447,3011,2955,1708,1653,1603,1578,1515,1486,1457,1312,1211,1164/cm.[α]D=-60.3°(CHCl3,C=1.00,23℃).No.1k-7CDCl3 300MHz1.04-2.22(14H,m),2.36(2H,t,J=7.2Hz),2.57(1H,m),3.87(1H,m),5.30-5.44(2H,m),6.17(1H,d,J=8.7Hz),6.99-7.40(7H,m),7.73(2H,d,J=7.5Hz).IR(CHCl3)3449,3013,2955,1739,1708,1651,1609,1588,1522,1487,1243,1227,1169/cm.[α]D=-60.2°(CHCl3,C=0.92,23℃).No.1k-8CDCl3 300MHz1.04-2.25(14H,m),2.34(2H,t,J=7.5Hz),2.56(1H,m),3.87(1H,m),5.30-5.44(2H,m),6.19(1H,d,J=7.5Hz),6.83-6.94(6H,m),7.69(2H,d,J=8.7Hz).IR(CHCl3)3599,3455,3012,2955,1711,1644,1604,1577,1524,1507,1492,1290,1236,1197,1170/cm.[α]D=-47.7°(CHCl3,C=1.01,22℃).No.1k-9CDCl3 300MHz1.04-2.20(14H,m),2.31(3H,s),2.36(2H,t,J=7.2Hz),2.56(1H,m),3.86(1H,m),5.30-5.43(2H,m),6.16(1H,d,J=7.2Hz),7.00-7.11(6H,m),7.74(2H,d,J=8.7Hz).1R(CHCl3)3450,3010,2955,1750,1709,1651,1609,1596,1523,1489,1370,1247,1227,1183/cm.[α]D=-54.7°(CHCl3,C=1.01,22℃).No.1k-10CDCl3 300MHz1.04-2.22(14H,m),2.35(2H,t,J=7.2Hz),2.56(1H,m),3.82(3H,s),3.86(1H,m),5.30-5.43(2H,m),6.17(1H,d,J=6.9Hz),6.89-7.01(6H,m),7.70(2H,d,J=8.7Hz).IR(CHCl3) 3023,2955,1742,1708,1649,1613,1602,1577,1522,1507,1490,1227,1210,1170/cm.[α]D=-58.1°(CHCl3,C=1.01,22℃).No.1m-1CDCl3 300MHz1.06-2.25(14H,m),2.32(2H,t,J=7.4Hz),2.61(1H,m),3.63 (3H,s),3.91 (1H,m),5.33-5.47(2H,m),6.24(1H,d,J=6.9Hz),7.35-7.38(3H,m),7.53-7.60(4H,m),7.75-7.78(2H,m).IR(CHCl3)3438,3008,2946,2875,2212,1732,1650,1605,1519,1496/cm.[α]D=+76°(CHCl3,C=1.39,24℃)No.1m-2CDCl3 300MHz1.05-2.20(14H,m),2.36(2H,t,J=6.2Hz),2.59(1H,m),3.89(1H,m),5.29-5.48(2H,m),6.26(1H,d,J=7.0Hz),7.26-7.38(3H,m),7.52- 7.60(4H,m),7.73-7.77(2H,m).IR(CHCl3)3444,3012,2952,2874,2664,2214,1718(sh),1708,1649,1605,1520,1498/cm.[α]D=+81.4°(CHCl3,C=1.01,23℃)No.1m-3CDCl3 300MHz1.06-2.23(14H,m),2.32(2H,t,J=7.0Hz),2.62(1H,m),3.63(3H,s),3.93(1H,m),5.30-5.50(2H,m),6.28(1H,d,J=7.0Hz),7.38-7.51(3H,m),7.58-7.67(4H,m),7.83-7.88(2H,m).IR(CHCl3)3438,3008,2948,2875,1783(w),1727,1650,1608,1580(w),1523,1501,1482/cm.[α]D= +59°(CHCl3,C=1.49,25℃)No.1m-4CDCl3 300MHz1.08-2.25(14H,m),2.36(2H,t,J=7.4Hz),2.59(1H,m),3.91(1H,m),5.28-5.48(3H,m),6.29(1H,d,J=7.4Hz),7.38-7.50(3H,m),7.61-7.67(4H,m),7.81-7.86(2H,m).IR(CHCl3)3436,3010,2948,2868,1727,1715(sh),1649,1615(w),1524,1502,1482,1372/cm.[α]D=+72°(CHCl3,C=0.98,25℃)No.1m-5CDCl3 300MHz1.09-2.20(14H,m),2.32(2H,t,J=7.2Hz),2.63(1H,m),3.63(3H,s),3.92(1H,m),5.31-5.51(2H,m),6.35(1H,d,J=7.0Hz),7.51-7.60(3H,m),7.92-7.97(6H,m).IR(CHCl3)3436,3008,2946,2875,1727,1652,1608(w),1515,1484/cm.[α]D=+82°(CHCl3,C=0.99,25℃)No.1m-6CDCl3 300MHz1.09-2.23(14H,m),2.37(2H,t,J=7.2Hz),2.60(1H,m),3.92(1H,m),5.30-5.49(2H,m),6.32(1H,d,J=7.4Hz),7.51-7.55(3H,m),7.85-7.98(6H,m).IR(CHCl3)3436,3010,2950,2875,2670,1727,1715(sh),1650,1605(w),1515,1484/cm.[α]D=+84°(CHCl3,C=1.54,25℃)No.1m-7CDCl3 300MHz1.03-2.18(14H,m),2.32(2H,t,J=7.4Hz),2.59(1H,m),3.64(3H,s),3.89(1H,m),5.29-5.49(2H,m),6.16(1H,d,J=7.8Hz),6.98-7.06(4H,m),7.14-7.20(1H,m),7.34-7.41(2H,m),7.73-7.78(2H,m).IR(CHCl3)3438,3008,2946,2868,1727,1648,1610,1586,1519,1485/cm.[α]D=+54°(CHCl3,C=1.29,25℃).No.1m-8CDCl3 300MHz1.06-2.21(14H,m),2.36(2H,t,J=7.5Hz),2.58(1H,m),3.88(1H,m),5.31- 5.46(2H,m),6.17(1H,d,J=6.9Hz),6.99-7.05(4H,m),7.15-7.21(1H,m),7.36-7.41(2H,m),7.72-7.75(2H,m).IR(CHCl3)3436,3010,2948,2868,2675,1730(sh),1709,1647,1608,1586,1520,1485/cm.[α]D=+56°(CHCl3,C=0.97,25℃)No.1m-9CDCl3 300MHz1.05-2.18(14H,m),2.29-2.34(5H,m),2.59(1H,m),3.64(3H,s),3.89(1H,m),5.32-5.46(2H,m),6.16(1H,d,J=7.5Hz),7.00-7.11(6H,m),7.74-7.77(2H,m).IR(CHCl3)3440,3010,2946,2868,1729,1649,1595,1519,1488/cm.[α]D=+47°(CHCl3,C=0.82,25℃).No.1m-10CDCl3 300MHz 1.04-2.20(14H,m),2.31-2.39(5H,m),2.57(1H,m),3.87(1H,m),5.28-5.47(2H,m),6.17(1H,d,J=7.0Hz),6.99-7.12(6H,m),7.72-7.76(2H,m).IR(CHCl3)3674,3572,3438,3010,2948,2868,2626,1748,1710,1648,1615,1595,1520,1489/cm.[α]D=+51°(CHCl3,C=0.91,25℃)No.1m-11CDCl3 300MHz1.04-2.16(14H,m),2.31(2H,t,J=7.2Hz),2.59(1H,m),3.63(3H,s),3.89(1H,m),5.29-5.49(2H,m),6.24(1H,d,J=7.4Hz),6.54(1H,s),6.83-6.93(6H,m),7.69-7.73(2H,m).IR(CHCl3)3674,3588,3438,3296,3010,2946,2868,1725,1646,1603,1520,1504,1489/cm.[α]D=+51°(CHCl3,C=0.91,25℃)No.1m-12CDCl3 300MHz1.04-2.21(14H,m),2.33(2H,t,J=8.0Hz),2.56(1H,m),3.87(1H,m),5.28- 5.48(2H,m),6.23(1H,d,J=8.0Hz),6.75(1H,m),6.87-6.94(6H,m),7.66-7.71(2H,m),9.63(1H,brs).IR(CHCl3)3674,3582,3436,3275,3010,2950,2868,2675,1727,1710(sh),1643,1603,1522,1504,1490/cm.[α]D=+30°(CHCl3,C=0.97,25℃)No.1m-13CDCl3 300MHz1.01-2.18(14H,m),2.31(2H,t,J=7.4Hz),2.58(1H,m),3.63(3H,s),3.82(3H,s),3.89(1H,m),5.29-5.48(2H,m),6.14(1H,d,J=7.0Hz),6.88- 7.02(6H,m),7.70-7.74(2H,m).IR(CHCl3)3442,3402,3004,2946,2868,1727,1648,1600,1518,1499/cm.[α]D=+42°(CHCl3,C=1.82,26℃)No.1m-14CDCl3 300MHz1.05-2.21(14H,m),2.35(2H,t,J=7.2Hz),2.55(1H,m),3.82(3H,s),3.88(1H,m),5.27-5.46(2H,m),6.16(1H,d,J=7.2Hz),6.88-7.02(6H,m),7.68-7.73(2H,m).IR(CHCl3)3438,3012,2948,2870,2650,1730(sh),1709,1647,1615(sh),1601,1519,1492/cm.[α]D=+64°(CHCl3,C=0.70,25℃)No.1m-15CDCl3 300MHz1.05-2.20(14H,m),2.29-2.36(5H,m),2.62(1H,m),3.63(3H,s),3.92(1H,m),5.30-5.50(2H,m),6.25(1H,d,J=7.2Hz),7.16-7.21(2H,m),7.59-7.64(4H,m),7.83-7.87(2H,m).IR(CHCl3)3446,3010,2946,2868,1745(sh),1728,1650,1615,1525,1507,1486/cm.[α]D=+65.0°(CHCl3,C=1.02,23℃)No.1m-16CDCl3 300MHz1.08-2.21(14H,m),2.34-2.40(5H,m),2.59(1H,m),3.90(1H,m),5.29-5.48(2H,m),6.29(1H,d,J=7.0Hz),7.18(2H,d,J=8.6Hz),7.58-7.64(4H,m),7.83(2H,d,J=8.2Hz).IR(CHCl3)3438,3012,2948,2870,2622,1749,1710,1649,1610,1526,1508,1487/cm.[α]D=+66°(CHCl3,C=1.21,24℃)No.1m-17CDCl3 300MHz1.06-2.19(14H,m),2.32(2H,t,J=7.2Hz),2.62(1H,m),3.63(3H,s), 3.93(1H,m),5.30-5.50(2H,m),6.32(1H,d,J=7.6Hz),6.41(1H,s),6.94 (2H,d,J=9.0Hz),7.47(2H,d,J=9.0Hz),7.58(2H,d,J=8.6Hz),7.81(2H,d,J=8.6Hz).IR(CHCl3)3580,3434,3284,3010,2946,2868,1726,1646,1606,1528,1490/cm. [α]D=+62.4°(CHCl3,C=1.01,23℃)No.1m-18CDCl3+CD3OD 300MHz1.11-2.18(14H,m),2.32(2H,t,J=7.4Hz),2.59(1H,m),3.88(1H m),5.30-5.49(2H,m),6.55(1H,d,J=7.0Hz),6.92(2H,d,J=8.6Hz),7.47(2H,d,J=8.6Hz),7.59(2H,d,J=8.6Hz),7.79(2H,d,J=8.2Hz).IR(Nujol)3398,3175,2725,1696,1635,1601,1531,1510/cm.[α]D=+99.5°(CH3OH,C=1.011,25℃)No.1m-19CDCl3 300MHz1.05-2.20(14H,m),2.32(2H,t,J=7.4Hz),2.61(1H,m),3.63(3H,s),3.86(3H,s),3.94(1H,m),5.30-5.50(2H,m),6.24(1H,d,J=7.0Hz),6.99(2H,d,J=8.6Hz),7.53-7.63(4H,m),7.82(2H,d,J=8.6Hz).IR(CHCl3)3440,3006,2946,2875,1726,1649,1606,1527,1510,1489/cm.[α]D=+68°(CHCl3,C=0.88,26℃)No.1m-20CDCl3 300MHz1.09-2.20(14H,m),2.35(2H,t,J=7.3Hz),2.58(1H,m),3.85(3H,s),3.89(1H,m),5.28-5.48(2H,m),6.35(1H,d,J=7.2Hz),6.98(2H,d,J=8.8Hz),7.51-7.61(4H,m),7.81(2H,d,J=8.4Hz),8.34(1H,brs).IR(CHCl3)3446,3012,2952,2881,2640,1730(sh),1707,1647,1606,1527,1510,1489/cm.[α]D=+83°(CHCl3,C=1.00,25℃).No.1m-21CDCl3 300MHz1.05-2.14(14H,m),2.37(2H,t,J=7.2Hz),2.51(1H,m),3.81(1H,m),5.34-5.46(2H,m),6.11(1H,d,J=7.5Hz),7.33-7.48(3H,m),7.53-7.55(2H,m).IR(CHCl3)3420,3250,3008,2948,2870,2660,2210,1735(sh),1705,1645,1503,1441,1409/cm.[α]D=+59.2±1.0°(CHCl3,C=1.023,22℃).No.1m-22CDCl3 300MHz1.05-2.17(14H,m),2.37(2H,t,J=7.2Hz),2.52(1H,m),3.82(1H,m),5.32-5.47(2H,m),6.20(1H,d,J=7.6Hz),7.38-7.53 (3H,m),7.58-7.61(6H,m),9.11(1H,brs).IR(CHCl3)3420,3250,3010,2984,2870,2675,2208,1730(sh),1705,1640,1500,1406/cm.[α]D=+57.4°(CHCl3,C=1.83,23℃).No.1m-23CDCl3 300MHz1.05-2.18(14H,m),2.31(2H,t,J=7.5Hz),2.60(1H,m),3.63(3H,s),3.90(1H,m),5.32-5.47(2H,m),6.22(1H,d,J=6.9Hz),7.40-7.49(3H,m),7.76-7.79(2H,m).IR(CHCl3)3438,3008,2946,2868,1727,1651,1603,1585,1512,1484/cm.[α]D=+52°(CHCl3,C=1.49,25℃).No.1m-24 CDCl3 300MHz 1.05-2.21(14H,m),2.36(2H,t,J=7.2Hz),2.57(1H,m),3.89(1H,m),5.28-5.47(2H, m),6.22(1H,d,J=7.0Hz),7.39-7.55(3H,m),7.73-7.79(2H,m). IR(CHCl3)3676,3572,3436,3010,2948,2875,1730(sh),1709,1650,1600,1580,1 514,1484/cm. [α]D=+57°(CHCl3,C=0.97,26℃). No.1m-25 CDCl3 300MHz 1.04-2.18(14H,m),2.28-2.35(5H,m),2.59(1H,m),3.62(3H,s),3.88(1H,m),5.29-5. 49(2H,m),6.20(1H,d,J=7.2Hz),7.15(2H,d,J=9.0Hz),7.80(2H,d,J=8.8Hz).IR(CHCl3)3436,3010,2946,2868,1752,1727,1653,1602,1519,1491/cm. [α]D=+53°(CHCl3,C=1.63,25℃).No.1m-26CDCl3 300MHz1.05-2.19(14H,m),2.32-2.38(5H,m),2.56(1H,m),3.88(1H,m),5.29-5.47(2H,m),6.25(1H,d,J=7.4Hz),7.15(2H,d,J=9.0Hz),7.78(2H,d,J=8.6Hz).IR(CHCl3)3434,3016,3006,2948,2880,2622,1752,1730(sh),1710,1651,1605,1520,1492/cm.[α]D=+58°(CHCl3,C=3.68,24℃)No.1m-27CDCl3 300MHz1.05-2.16(14H,m),2.30(2H,t,J=7.5Hz),2.57(1H,m),3.62(3H,s),3.87(1H,m),5.27-5.47(2H,m),6.32(1H,d,J=7.4Hz),6.85(2H,d,J=8.6Hz),7.62(2H,d,J=8.6Hz),8.35(1H,s).IR(CHCl3)3580,3450,3216,3010,2946,2868,1726,1640,1608,1584,1528,1496/cm.[α]D=+56.2°(CHCl3,C=0.713,23℃)No.1m-28CDCl3 200MHz1.10-2.25(14H,m),2.32(2H,t,J=7.2Hz),2.55(1H,brs),3.82-3.93(1H,m),5.27-5.47(2H,m),6.25 (1H,d,J=7.4Hz),6.86(2H,d,J=8.6Hz),7.62(2H,d,J=8.6Hz).IR(CHCl3)3438,3242,2675,1730(sh),1708,1639,1607,1585/cm.No.1m-29CDCl3 300MHz1.05-2.18(14H,m),2.31(2H,t,J=7.4Hz),2.58(1H,m),3.64(3H,s),3.85(3H,s),3.89(1H,m),5.29-5.48(2H,m),6.14(1H,d,J=6.6Hz),6.92(2H,d,J=9.0Hz),7.74(2H,d,J=9.0Hz).IR(CHCl3)3445,3008,2946,2858,1727,1646,1606,1578,1523,1493/cm.[α]D=+53°(CHCl3,C=2.03,24℃)No.1m-30CDCl3 300MHz1.04-2.21(14H,m),2.36(2H,t,J=7.3Hz),2.56(1H,m),3.85(3H,s),3.88(1H,m),5.27-5.46(2H,m),6.15(1H,d,J=7.2Hz),6.92(2H,d,J=8.6Hz),7.73(2H,d,J=8.6Hz)IR(CHCl3)3440,3010,2950,2870,2645,1727,1710(sh),1646,1606,1575,1524,1494/cm.[α]D=+62°(CHCl3,C=1.10,24℃).No.1m-31CDCl3+CD3OD 300MHz1.16-2.20(14H,m),2.31(2H,t,J=7.2Hz),2.59(1H,m),3.85(1H,m),5.31-5.51(2H,m),7.13-7.21(1H,m),7.31-7.42(2H,m),7.68-7.93(6H,m).IR(液蠟)3344,3175,2715,2675,1699,1631,1566/cm. [α]D=+67°(CH3OH,C=1.01,24℃). No.1m-32 CDCl3 200MHz 1.09-2.23(14H,m),2.33(2H,t,J=7.1Hz),2.57(1H,brs),3.40-3.93(9H,m),4.41(1H, brs),5.29-5.48(2H,m),6.44(1H,d,J=7.4Hz),7.43(2H,d,J=8.2Hz),7.80(2H,d,J=7. 8Hz). IR(CHCl3)3434,3354,1726,1720(sh),1660(sh),1626/cm. No.1m-33 CDCl3 200MHz 1.14-2.25(14H,m),2.37(2H,t,J=7.3Hz),2.64(1H,brs),3.93-4.01(1H,m),5.30-5.5 1(2H,m),6.47(1H,d,J=7.4Hz),7.63-7.74(2H,m),7.79(2H,s),7.89-7.93(1H,m),8.00(1H,dd,J=2.3,1.0Hz),8.30(1H,d,J=1.0Hz),8.65-8.73(2H,m).IR(CHCl3)3450,2675,1728,1707,1649,1528,1509/cm.[α]D=+82.8±1.2°(CHCl3,C=1.01,23℃).No.2a-1[α]D=+69.0°(MeOH,C=1.01,25℃)No.2a-2CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.15和1.24(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),4.30(1H,m).5.35-5.52(2H,m),6.32(1H,d,J=8.7Hz),7.36-7.49(3H,m),7.58-7.62(2H,m),7.66和 7.80(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3116,3014,2925,2870,2663,1708,1651,1610,1524,1504,1484,1472/cm.[α]D=+64.1°(MeOH,C=1.02,25℃).No.2a-3[α]D=+76.6°(MeOH,C=1.18,26℃).No.2a-4CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.15和 1.25(每個(gè)3H,每個(gè)s),1.64-2.51(14H,m),4.31(1H,m),5.36-5.53(2H,m),6.33(1H,d,J=8.4z),7.50-7.56(3H,m),7.85-7.98(6H,m).IR(CHCl3)3515,3452,3014,2925,2870,1740,1708,1654,1517,1486,1470/cm.[α]D=+79.5°(MeOH,c=1.18,22℃).No.2a-5 CD3OD 300MHz 0.98(1H,d,J=9.9Hz),1.18和 1.25(每個(gè)3H,每個(gè)s),1.56-1.71(3H,m),1.98-2.40(11H,m),4.17(1H,m),5.41-5.52(2H,m),7.52-7.61(3H,m),7.91-8.01(6H,m). IR(KBr)3416,3063,2983,2921,2869,1704,1643,1566,1518,1488,1408/cm.[α]D=+62.0°(MeOH,C=1.00,25℃).No.2a-6[α]D=+64.1°(MeOH,C=1.01,25℃).No.2a-7[α]D=+65.3°(MeOH,C=0.99,25℃).No.2a-8[α]D=+74.0°(MeOH,C=1.01,25℃).No.2a-9[α]D=+71.0°(MeOH,C=1.10,25℃).No.2a-10[α]D=+74.7°(MeOH,C=1.00,25℃).No.2a-11[α]D=+72.1°(MeOH,C=1.00,25℃).No.2a-12[α]D=+53.1°(CHCl3,C=1.01,26℃).m.p.155.0-156.0℃No.2a-13 CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.18和1.25(每個(gè)3H,每個(gè)s),1.63-2.40(14H,m),4.30(1H,m),5.46-5.58(2H,m),6.44(1H,d,J=8.4Hz),7.49和7.77(每個(gè)2H,每個(gè) d,J=8.7Hz),7.54(1H,s).IR(CHCl3)3689,3378,3028,3014,2924,1713,1652,1602,1522,1496/cm.[α]D=+78.3°(MeOH,C=0.84,25℃).m.p.205.0-206.0℃No.2a-14[α]D=+72.5°(MeOH,C=1.07,25℃).No.2a-15 CDCl3 300MHz0.99(1H,d,J=9.9Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.55-2.44(14H,m),4.27(1H,m),5.30-5.50(2H,m),6.29(1H,d,J=9.0Hz),7.11和7.20(每個(gè)1H,每個(gè)d,J=16.2Hz),7.29-7.55(5H,m),7.57和7.72(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3453,3083,3022,3013,2925,2870,1708,1650,1607,1560,1522,1496/cm.[α]D=+72.3°(MeOH,C=1.00,27℃).m.p.115.0-117.0℃No.2a-16 CDCl3 300MHz 0.92(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.50-2.48(14H,m),3.6 2(3H,s),4.29(1H,m),5.30-5.50(2H,m),6.20(1H,d,J=8.7Hz),6.59和6.68(每個(gè)1H,每個(gè)d,J=12.3Hz),7.23(5H,s),7.29和7.59(每個(gè)2H,每個(gè)d,J=8.1Hz).IR(CHCl3)3453,3024,3016,2924,2870,1730,1651,1607,1520,1495/cm.[α]D=+56.8°(MeOH,C=1.04,24℃).No.2a-17CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.50-2.38(14H,m),4.26(1H,m),5.30-5.50(2H,m),6.23(1H,d,J=8.4Hz),6.59和6.70(每個(gè)1H,每個(gè)d,J=12.3Hz),7.23(5H,s),7.30和7.57(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3452,3081,3019,3014,2925,2870,2665,1708,1650,1607,1521,1495/cm.[α]D=+61.6°(MeOH,C=1.00,27℃).No.2a-18CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),3.61(3H,s),4.31(1H,m),5.35-5.51(2H,m),6.33(1H,d,J=8.4Hz),7.48-7.64(4H,m),7.79-7.83(2H,m),7.91(1H,dt,J=1.5和7.8Hz),8.01(1H,dt,J=1.5和7.8Hz),8.13(1H,t,J=1.5Hz).IR(CHCl3)3450,3026,3013,2925,2870,1730,1659,1600,1510/cm.[α]D=+56.0°(MeOH,C=1.01,25℃).No.2a-19CDCl3 300MHz0.95(1H,d,J=9.9Hz),1.14和1.21(每個(gè)3H,每個(gè)s),1.53-2.60(14H,m),4.25(1H,m),5.35-5.64(2H,m),7.21(1H,d,J=7.8Hz),7.49-7.68(4H,m),7.76-7.84(3H,m),8.25(1H,m),8.43(1H,m).IR(CHCl3)3382,3196,3025,3015,2925,2870,1725,1652,1599,1577,1521/cm.[α]D=+55.9°(MeOH,C=1.00,25℃).No.2a-20CDCl3300MHz0.98(1H,d,J=10.2Hz),1.13和1.24(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),3.62(3H,s),4.31(1H,m),5.35-5.51(2H,m),6.24(1H,d,J=8.4Hz),7.40-7.52(3H,m),7.71-7.76(2H,m).IR(CHCl3)3453,3025,3013,2925,2870,1730,1753,1579,1514,1486/cm.[α]D=+61.2°(MeOH,C=1.04,25℃).No.2a-21CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.13和1.23(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.28(1H,m),5.34-5.51(2H,m),6.27(1H,d,J=8.7Hz),7.41-7.53(3H,m),7.71-7.74(2H,m).IR(CHCl3)3452,3063,3027,3014,2925,2871,1708,1652,1578,1515,1486/cm.[α]D=+62.0°(MeOH,C=1.01,27℃).No.2a-22d6-DMSO 300MHz0.86(1H,d,J=9.9Hz),1.10和1.16(每個(gè)3H,每個(gè)s),1.42-1.52(3H,m),1.85-2.46(11H,m),3.98(1H,m),5.32-5.43(2H,m),7.41(3H,m),7.88(2H,d,J=6.6Hz),8.19(1H,d,J=6.6Hz).IR(KBr)3367,3060,2984,2922,2868,1634,1563,1529,1487/cm.[α]D=+47.7°(MeOH,C=1.00,25℃).No.2a-23[α]D=+62.7°(MeOH,C=1.01,27℃).No.2a-24CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.14和1.25(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.31(1H,m),5.36-5.52(2H,m),6.34(1H,d,J=8.4Hz),7.47-7.52(2H,m),7.59-7.64(1H,m),7.78-7.83(6H,m).IR(CHCl3)3449,3027,3013,2925,2869,1708,1656,1599,1518,1493/cm.[α]D=+63.1°(MeOH,C=1.00,25℃).No.2a-25[α]D=+35.1°(MeOH,C=1.00,25℃).No.2a-26[α]D=+35.5°(MeOH,C=1.02,25℃).No.2a-27CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),3.63(3H,s),4.29(1H,m),5.36-5.51(2H,m),6.18(1H,d,J=8.4Hz),7.01和7.71(每個(gè)2H,每個(gè)d,J=8.7Hz,),6.98-7.05(2H,m),7.16(1H,t,J=7.5Hz),7.34-7.41(2H,m).IR(CHCl3)3455,3024,3016,2924,2870,1730,1651,1588,1520,1487/cm.[α]D=+56.4°(MeOH,C=1.01,25℃).No.2a-28CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.26(1H,m),5.34-5.51(2H,m),6.20(1H,d,J=9.0Hz),7.01和7.70(每個(gè)2H,每個(gè)d,J=9.0Hz,),6.98-7.15(2H,m),7.17(1H,t,J=7.5Hz),7.34-7.40(2H,m).IR(CHCl3)3454,3031,3018,2925,2870,1708,1650,1588,1523,1487/cm.[α]D=+56.2°(MeOH,C=1.00,25℃).No.2a-29[α]D=+53.0°(MeOH,C=1.03,25℃).No.2a-30CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.10和1.23(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.25(1H,m),5.30-5.50(2H,m),6.23(1H,d,J=8.7Hz),6.36(1H,s),7.26-7.39(10H,m),7.60和 7.68(每個(gè)2H,每個(gè)d,J=8.4Hz,).IR(CHCl3)3451,3088,3064,3029,3014,2925,2869,1707,1652,1522,1495/cm.[α]D=+54.2°(MeOH,C=1.00,25℃).No.2a-31CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),3.63(3H,s),4.31(1H,m),5.30-5.50(2H,m),6.26(1H,d,J=8.4Hz),6.90(1H,t,J=7.4Hz),7.13(1H,d,J=8.7Hz),7.29(2H,t,J=8.0Hz),7.67-7.75(5H,m),7.82(1H,s).IR(Nujol)3380,3244,1723,1638,1601,1578,1535,1495/cm.[α]D=+73.6°(MeOH,C=0.50,26℃)。m.p.133.0-134.0℃No.2a-32[α]D=+56.1°(MeOH,C=1.02,26℃).No.2a-33CDCl3 300MHz0.95(1H,d,J=10.2Hz),1.10和1.21(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),4.25(1H,m),5.13(2H,s),5.30-5.70(3H,m),6.41(1H,d,J=8.2Hz),6.89(1H,s),7.09(1H,s),7.17和7.72(每個(gè)2H,每個(gè)d,J=8.2Hz),7.62(1H,s).IR(CHCl3)3450,3125,3031,3013,2925,2870,2467,1917,1708,1654,1615,1575,1523,1497/cm.[α]D=+55.2°(MeOH,C=1.01,26℃).No.2a-34[α]D=+72.9°(MeOH,C=1.03,25℃).No.2a-35CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.13和1.24(每個(gè)3H,每個(gè)s),1.52-2.48(14H,m),4.28(1H,m),5.35-5.51(2H,m),6.28(1H,d,J=8.7Hz),7.34-7.37(3H,m),7.52-7.55(2H,m),7.58和 7.71(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3515,3452,3030,3012,2925,2870,1739,1708,1652,1607,1555,1521,1497/cm.[α]D=+74.3°(MeOH,C=1.01,25℃).No.2a-36[α]D=+23.4°(MeOH,C=1.07,25℃).No.2a-37CDCl3 300MHz0.83(1H,d,J=10.5Hz),0.95和1.18(每個(gè)3H,每個(gè)s),1.44-2.46(14H,m),3.92(1H,m),5.34-5.52(3H,m),7.26-7.54(9H,m),7.62(1H,s).IR(CHCl3)3432,3310,3189,3023,3014,2924,2870,1704,1610,1594,1523,1487/cm.[α]D=+25.3°(MeOH,C=1.00,26℃).No.2a-38[α]D=+70.9°(MeOH,C=1.02,25℃).No.2a-39[α]D=+70.6°(MeOH,C=1.01,25℃).No.2a-40[α]D=+74.7°(MeOH,C=1.00,25℃).No.2a-41[α]D=+72.1°(MeOH,C=1.01,24℃).No.2a-42[α]D=+69.2°(MeOH,C=1.00,25℃).No.2a-43[α]D=+70.8°(MeOH,C=1.00,25℃).No.2a-44[α]D=+60.4°(MeOH,C=1.00,26℃).No 2a-45CDCl3 300MHz0.97(1H,d,J=9.9Hz),1.13和1.23(每個(gè)3H,每個(gè)s),1.55-2.52(14H,m),4.29(1H,m),5.34-5.54(2H,m),6.33(1H,d,J=9.0Hz),7.10(1H,t,J=7.4Hz),7.34(2H,t,J=7.4Hz),7.52(2H,m),7.68和7.75(每個(gè)2H,每個(gè)d,J=8.4Hz),7.80(1H,s),8.10(1H,s),10.09(1H,s).IR(CHCl3)3393,3195,3093,3033,3013,2925,2870,1698,1656,1598,1537,1498/cm.[α]D=+59.4°(MeOH,C=1.01,24℃).No.2a-46[α]D=+63.5°(MeOH,C=1.00,25℃).No.2a-47CDCl3 300MHz0.97(1H,d,J=9.9Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),4.29(1H,m),5.35-5.52(2H,m),6.32(1H,d,J=8.7Hz),7.26(1H,m),7.41(2H,t,J=7.8Hz),7.64(2H,d,J=7.5Hz),7.73和7.77(每個(gè)2H,每個(gè)d,J=8.4Hz),7.95(1H,s),9.20(1H,s),10.38(1H,s).IR(CHCl3)3450,3339,3003,2992,2925,2870,1706,1653,1596,1523,1495/cm.[α]D=+63.3°(MeOH,C=1.00,25℃).No.2a-48[α]D=+63.8°(MeOH,C=1.00,24℃).No.2a-49CDCl3 300MHz1.00(1H,d,J=10.5Hz),1.17和1.26(每個(gè)3H,每個(gè)s),1.55-2.52(14H,m),4.34(1H,m),5.36-5.54(2H,m),6.35(1H,d,J=9.0Hz),7.50-7.62(3H,m),7.90和8.33(每個(gè)2H,每個(gè)d,J=8.4Hz),8.21(2H,m).IR(CHCl3)3451,3029,3022,3016,2925,2870,1708,1655,1542,1508,1498,1471,1459/cm.[α]D=+63.5°(MeOH,C=1.02,25℃).m.p.135.0-137.0℃No.2a-50[α]D=+68.9°(MeOH,C=1.01,24℃).No.2a-51 d6-DMSO 300MHz0.87(1H,d,J=9.9Hz),1.10和1.17(每個(gè)3H,每個(gè)s),1.40-1.60(3H,m),1.90-2.40(11H,m),3.98(1H,m),5.35-5.46(2H,m),7.64(1H,s),7.65和7.91(每個(gè)2H,每個(gè)d,J=8.7Hz),8.06(1H,d,J=6.0Hz),9.32(1H,brs).IR(KBr)3385,2962,1734,1707,1632,1529,1498/cm.[α]D=+68.4°(MeOH,C=1.01,24℃).No.2a-52[α]D=+76.2°(MeOH,C=1.01,24℃).No.2a-53[α]D=+73.9°(MeOH,C=1.02,24℃).No.2a-54[α]D=+68.1°(MeOH,C=1.00,24℃).No.2a-55[α]D=+67.8°(MeOH,C=1.00,24℃).No.2a-56[α]D=+65.4°(MeOH,C=1.03,25℃).No.2a-57[α]D=+63.4°(MeOH,C=1.01,24℃).No.2a-58[α]D=+66.6°(MeOH,C=1.01,24℃).No.2a-59[α]D=+65.5°(MeOH,C=1.00,24℃).No.2a-60[α]D=+60.9°(MeOH,C=1.02,25℃).No.2a-61CDCl3 300MHz0.97(1H,d,J=10.0Hz),1.10和1.22(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),4.26(1H,m),5.30-5.54(2H,m),6.28(1H,d,J=8.6Hz),6.60和6.82(每個(gè)1H,每個(gè)d,J=12.4Hz,),7.12(2H,d,J=6.0Hz),7.25和7.62(每個(gè)2H,每個(gè)d,J=8.6Hz),8.47(2H,d,J=6.0Hz).IR(CHCl3)3452,3027,3019,3013,2925,2870,2480,1708,1651,1606,1520,1494/cm.[α]D=+61.6°(MeOH,C=1.01,25℃).No.2a-62[α]D=+72.0°(MeOH,C=0.93,25℃).No.2a-63CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),4.29(1H,m),5.36-5.55(2H,m),6.35(1H,d,J=9.1Hz),7.04和7.27(每個(gè)1H,每個(gè)d,J=16.5Hz),7.37(2H,d,J=6.6Hz),7.56和7.76(每個(gè)2H,每個(gè)d,J=8.4Hz),8.57(2H,d,J=6.6Hz).IR(CHCl3)3452,3024,3018,3014,2925,2870,2470,1933,1708,1652,1605,1521,1496/cm.[α]D=+69.2°(MeOH,C=1.01,25℃).No.2a-64[α]D=+56.9°(MeOH,C=1.24,25℃).No.2a-65CDCl3 300MHz0.98(1H,d,J=10.5Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.54-2.46(14H,m),4.27(1H,m),5.23(2H,s),5.34-5.52(2H,m),6.26(1H,d,J=8.4Hz),7.32-7.45(5H,m),7.64和7.71(每個(gè)2H,每個(gè)d,J=8.4Hz),8.15(1H,s).IR(CHCl3)3452,3088,3065,3032,3013,2925,2870,1708,1653,1611,1559,1522,1496/cm.[α]D=+61.0°(MeOH,C=0.91,25℃).No.2a-66[α]D=+76.0°(MeOH,C=1.01,25℃).No.2a-67CDCl3 300MHz0.98(1H,d,J=10.4Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.54-2.46(14H,m),4.28(1H,m),5.32-5.53(2H,m),6.27(1H,d,J=8.6Hz),6,92-7.31(每個(gè)1H,每個(gè)d,J=16.4Hz),7.02(1H,dd,J=5.8 和3.6Hz),7.12(1H,d,J=3.6Hz),7.24(1H,d,J=5.8Hz),7.51和7.70(每個(gè)2H,每個(gè)d,J=8.4Hz).IR(CHCl3)3453,3029,3013,2925,2870,1739,1650,1604,1524,1515,1494/cm.[α]D=+76.2°(MeOH,C=1.00,24℃).m.p.104.0-106.0℃No.2a-68[α]D=+57.7°(MeOH,C=1.01,25℃).No.2a-69CDCl3 300MHzo.99(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),4.28(1H,m),5.34-5.53(2H,m),6.29(1H,d,J=9.0Hz),6,54-6.74(每個(gè)1H每個(gè)d,J=12.oHz),7.02(1H,dd,J=4.8和 3.3Hz),6.97(1H,dd,J=3.3和1.2Hz),7.13(1H,dd,J=4.8和1.2Hz),7.44和7.70(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3453,3025,3010,2925,2870,1708,1650,1607,1559,1523,1493/cm.[α]D=+58.4°(MeOH,C=1.00,25℃).No.2a-70[α]D=+48.6°(MeOH,C=1.00,25℃).No.2a-71CDCl3 300MHz0.98(1H,d,J=10.2Hz)1.12和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),2.31(3H,s),4.26(1H,m),5.33-5.52(2H,m),6.20(1H,d,J=9.3Hz),7.02-7.11(6H,m),7.70(2H,d,J=9.0Hz).IR(CHCl3)3460,3031,3022,3011,2925,2870,1750,1708,1650,1608,1597,1523,1490/cm.[α]D=+48.9°(MeOH,C=1.01,25℃).No.2a-72[α]D=+51.2°(MeOH,C=1.02,25℃).No.2a-73CDCl3 300MHz0.97(1H,d,J=9.9Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),4.27(1H,m),5.32-5.52(2H,m),6.24(1H,d,J=9.0Hz),6.83-6.94(6H,m),7.65(2H,d,J=9.0Hz).IR(CHCl3)3598,3451,3199,3033,3012,2925,2870,1708,1642,1604,1524,1507,1491/cm.[α]D=+52.2°(MeOH,C=1.01,25℃).No.2a-74[α]D=+51.5°(MeOH,C=0.92,25℃).No.2a-75 CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.55-2.46(14H,m),3.82(3H,s),4.25(1H,m),5.32-5.52(2H,m),6.19(1H,d,J=8.7Hz),6.89-7.01(6H,m),7.65-7.68(2H,m).IR(CHCl3)3450,3025,3008,2925,2870,2837,1741,1649,1612,1521,1505,1490/cm.[α]D=+51.1°(MeOH,C=1.00,25℃).No.2a-76[α]D=+60.4°(MeOH,C=0.98,25℃).No.2a-77CDCl3 300MHz0.99(1H,d,J=10.5Hz),1.15和1.24(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),2.34(3H,s),4.29(1H,m),5.32-5.54(2H,m),6.32(1H,d,J=8.4Hz),7.19和7.60(每個(gè)2H,每個(gè)d,J=8.4Hz),7.63和7.79(每個(gè)2H,每個(gè)d,J=8.4Hz).IR(CHCl3)3452,3027,3012,2925,2870,1751,1709,1651,1611,1560,1527,1509,1489/cm.[α]D=+61.2°(MeOH,C=1.00,25℃).No.2a-78[α]D=+67.4°(MeOH,C=1.01,25℃).No.2a-79 CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.15和1.24(每個(gè)3H,每個(gè)s),1.54-2.54(14H,m),4.31(1H,m),5.32-5.54(2H,m),6.36(1H,d,J=8.2Hz),6.93和7.48(每個(gè)2H,每個(gè)d,J=8.6Hz),7.59和7.75(每個(gè)2H,每個(gè)d,J=8.4Hz).IR(CHCl3)3593,3448,3192,3030,3010,2925,2870,1708,1644,1608,1591,1559,1530,1516,1491/cm.[α]D=+65.8°(MeOH,C=1.01,25℃).No.2a-80[α]D=+66.9°(MeOH,C=1.01,25℃).No.2a-81 CDCl3 300MHz0.99(1H,d,J=10.5Hz),1.15和1.24(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),3.86(3H,s),4.29(1H,m),5.34-5.52(2H,m),6.20(1H,d,J=8.7Hz),6.99和7.55(每個(gè)2H,每個(gè)d,J=9.0Hz),7.61和7.77(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3450,3009,2925,2870,2838,1740,1708,1650,1608,1557,1528,1512,1491/cm.[α]D=+66.2°(MeOH,C=1.01,25℃).No.2a-82[α]D=+57.7°(MeOH,C=1.02,24℃).No.2a-83CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),2.33(3H,s),4.26(1H,m),5.32-5.52(2H,m),6.25(1H,d,J=8.7Hz),7.16和7.75 (每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3452,3030,3022,3012,2925,2870,1754,1709,1654,1604,1585,1522,1493/cm.[α]D=+57.4°(MeOH,C=1.01,24℃).No.2a-84[α]D=+57.8°(MeOH,C=1.01,24℃).No.2a-85CDCl3 300MHz0.95(1H,d,J=10.2Hz),1.12和1.22(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),4.25(1H,m),5.32-5.52(2H,m),6.28(1H,d,J=8.7Hz),6.87和7.57(每個(gè)2H,每個(gè)d,J=9.0Hz).IR(CHCl3)3590,3450,3166,3019,3012,2925,2871,1708,1637,1608,1583,1531,1498/cm.[α]D=+56.0°(MeOH,C=1.01,24℃).No.2a-86[α]D=+59.3°(MeOH,C=1.01,22℃).No.2a-87CDCl3 300MHz0.98(1H,d,J=10.0Hz),1.13和1.23(每個(gè)3H,每個(gè)s),1.54-2.48(14H,m),3.85(3H,s),4.25(1H,m),5.32-5.53(2H,m),6.19(1H,d,J=8.8Hz),6.93和7.69(每個(gè)2H,每個(gè)d,J=9.0Hz).IR(CHCl3)3450,3030,3017,3012,2925,2870,2840,1740,1708,1647,1606,1575,1525,1496/cm.[α]D=+58.2°(MeOH,C=0.99,22℃).No.2a-88[α]D=+50.9°(MeOH,C=1.02,25℃).No.2a-89CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.18和1.26(每個(gè)3H,每個(gè)s),1.56-2.48(14H,m),4.29(1H,m),5.36-5.54(2H,m),7.03(1H,d,J=8.7Hz),7.21(1H,s),7.43(2H,m),7.74(1H,ddd,J=1.8,6.9和8.7Hz),8.22(1H,dd,J=1.8和8.1Hz).IR(CHCl3)3443,3087,3023,3014,2925,2870,1708,1685,1658,1630,1517,1466/cm.[α]D=+57.1°(MeOH,C=1.01,22℃).m.p.117.0-118.0℃No.2a-90[α]D=+54.1°(MeOH,C=1.01,22℃).No.2a-91CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.13和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),4.24(1H,m),5.34-5.52(2H,m),6.49-6.53(2H,m),7.11(1H,dd,J=0.9和3.6Hz),7.44(1H,dd,J=0.9和1.8Hz).IR(CHCl3)3437,3033,3022,3014,2925,2870,1739,1708,1655,1595,1520,1472/cm.[α]D=+55.0°(MeOH,C=1.00,22℃).No.2a-92[α]D=+50.3°(MeOH,C=1.00,22℃).No.2a-93CDCl3 300MHz0.95(1H,d,J=10.5Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),4.25(1H,m),5.34-5.52(2H,m),6.12(1H,d,J=8.7Hz),7.07(1H,dd,J=3.9和5.1Hz),7.45-7.48(2H,m).IR(CHCl3)3450,3023,3011,2925,2870,1739,1708,1645,1531,1501,1471/cm.[α]D=+49.1°(MeOH,C=1.02,24℃).No.2a-94[α]D=+51.5°(MeOH,C=1.00,24℃).No.2a-95CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),4.25(1H,m),5.34-5.56(2H,m),6.14(1H,d,J=8.7Hz),7 34(2H,d,J=2.0Hz),7.85(1H,t,J=2.0Hz).IR(CHCl3)3452,3114,3030,3013 2925,2870,1708,1649,1535,1498,1471/cm.[α]D=+55.5°(MeOH,C=1.00,25℃).m.p.87.0-88.0℃No.2a-96D3OD 300MHz0.94(1H,d,J=10.2Hz),1.13和1.22(每個(gè)3H,每個(gè)s),1.50-1.76(3H,m),1.94-2.39(11H,m),4.11(1H,m),5.39-5.49(2H,m),7.43-7.51(2H,m),8.05(1H,m).IR(KBr)3369,3084,2985,2921,2868,1630,1566,1538,1503/cm.[α]D=+38.8°(MeOH,C=1.01,22℃).No.2a-97CD3OD 300MHz0.93(1H,d,J=9.9Hz),1.13和1.22(每個(gè)3H,每個(gè)s),1.48-1.58(3H,m),1.96-2.36(11H,m),4.10(1H,m),5.35-5.50(2H,m),7.42-7.51(2H,m),8.06(1H,m).IR(KBr)3447,3087,2987,2922,2868,1629,1545,1501/cm.[α]D=+52.9°(MeOH,C=1.01,24℃).No.2a-98[α]D=+53.2°(MeOH,C=1.02,23℃).No.2a-99CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.12和1.22(每個(gè)3H,每個(gè)s),1.26-2.45(24H,m),4.25(2H,m),5.34-5.52(2H,m),6.18(1H,d,J=8.7Hz),6.91和7.66(每個(gè)2H,每個(gè)d,J=9.0Hz).IR(CHCl3)3455,3029,3019,2939,2862,1738,1709,1645,1605,1523,1494/cm.[α]D=+51.4°(MeOH,C=1.00,23℃).No.2a-100[α]D=+49.3°(MeOH,C=1.00,24℃).No.2a-101[α]D=+51.3°(MeOH,C=1.00,24℃).No.2a-102[α]D=+48.8°(MeOH,C=1.01,23℃).No.2a-103CDCl3 300MHz0.94(1H,d,J=10.2Hz),1.12和1.22(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),2.48(3H,d,J=O.3Hz),4.20(1H,m),5.32-5.54(2H,m),6.46(1H,brs),7.12(1H,d,J=9.OHz).IR(CHCl3)3415,3144,3029,3011,2926,2871,1708,1671,1598,1538,14564/cm[α]D=+49.6°(MeOH,C=1.01,23℃).No.2a-104[α]D=+77.0°(MeOH,C=1.02,23℃).No.2a-105CDCl3 300MHz93(1H,d,J=9.9Hz),1.09和1.21(每個(gè)3H,每個(gè)s),1.51-2.44(14H,m),3.90(6H,s),4.20(1H,m),5.38-5.50(2H,m),5.87(1H,d,J=9.0Hz),6.25和7.54(每個(gè)1H,每個(gè)d,J=15.6Hz),6.84(1H,d,J=8.1Hz),7.03(1H,d,J=1.8Hz),7.09(1H,dd,J=1.8 and 8.1Hz).IR(CHCl3)3439,3028,3012,2937,2871,2841,1739,1708,1661,1620,1600,1513/cm.[α]D=+77.3°(MeOH,C=1.01,23℃).No.2a-106[α]D=+67.O°(MeOH,C=1.00,25℃).No.2a-107[α]D=+66.6°(MeOH,C=1.01,24℃).m.p.168.0-170.0℃No.2a-108 [α]D=+61.8°(MeOH,C=1.00,22℃).No.2a-109CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.10和1.22(每個(gè)3H,每個(gè)s),1.51-2.45(14H,m),4.25(1H,m),5.33-5.49(2H,m),6.21(1H,d,J=8.7Hz),7.25和 7.60(每個(gè)2H,每個(gè)d,J=8.7Hz),7.33-7.41(5H,s).IR(CHCl3)3453,3062,3028,3014,2925,2870,1739,1708,1651,1594,1557,1515,1481/cm.[α]D=+61.0°(MeOH,C=1.01,22℃).No.2a-110CD3OD 300MHz0.94(1H,d,J=9.9Hz),1.13和1.22(每個(gè)3H,每個(gè)s),1.54-2.37(14H,m),4.12(1H,m),5.38-5.49(2H,m),7.25和7.68(每個(gè)2H,每個(gè)d,J=8.7Hz),7.41(5H,s)IR(KBr)3435,3058,2986,2920,2866,1635,1595,1562,1521,1482,1439,1411/cm.[α]D=+47.3°(MeOH,C=1.01,23℃).No.2a-111[α]D=+65.6°(MeOH,C=1.01,24℃).No.2a-112CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.51-2.46(14H,m),4.27(1H,m),5.35-5.50(2H,m),6.22(1H,d,J=8.4Hz),7.40和7.66(每個(gè)2H,每個(gè)d,J=9.0Hz).IR(CHCl3)3439,3028,3012,2937,2871,2841,1739,1708,1661,1620,1600,1513/cm.[α]D=+65.6°(MeOH,C=1.01,22℃).No.2a-113[α]D=+59.6°(MeOH,C=1.00,24℃).No.2a-114CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.12和1.24(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),4.29(1H,m),5.35-5.51(2H,m),6.28(1H,d,J=8.4Hz),7.70和7.83(每個(gè)2H,每個(gè)d,J=8.4Hz).IR(CHCl3)3439,3028,3012,2937,2871,2841,1739,1708,1661,1620,1600,1513/cm.[α]D=+60.6°(MeOH,C=1.01,22℃).No.2a-115[α]D=+59.7°(MeOH,C=0.99,24℃).No.2a-116CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),2.39(3H,s),4.27(1H,m),5.33-5.51(2H,m),6.24(1H,d,J=9.0Hz),7.23和7.62(每個(gè)2H,每個(gè)d,J=8.4Hz).IR(CHCl3)3439,3028,3012,2937,2871,2841,1739,1708,1661,1620,1600,1513/cm.[α]D=+59.7°(MeOH,c=0.99,24℃).No.2a-117[α]D=+56.7°(MeOH,c=1.00,23℃).No.2a-118CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.53-2.44(14H,m),4.23(1H,m),5.34-5.51(2H,m),6.02(2H,s),6.13(1H,d,J=8.7Hz),6.83(1H,dd,J=1.2and 7.8Hz),7.22-7.25(2H,m).IR(CHCl3)3453,3031,3020,3012,2924,2870,1740,1708,1650,1619,1605,1519,1504.1480/cm.[α]D=+57.2°(MeOH,c=1.02,23℃).No.2a-119CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.07和1.23(每個(gè)3H,每個(gè)s),1.51-2.44(14H,m),2.32(3H,s),4.26(1H,m),5.37-5.52(2H,m),6.40(1H,d,J=9.0Hz),7.09(1H,m),7.30(1H,m),7.46(1H,m),7.66(1H,m).IR(CHCl3)3443,3028,3012,2925,2870,1766,1747,1709,1657,1607,1516,1479/cm.[α]D=+53.2°(MeOH,c=0.99,21℃).No.2a-120CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.53-2.44(14H,m),4.30(1H,m),5.35-5.52(2H,m),6.42(1H,d,J=8.7Hz),6.85(1H,m),6.99(1H,dd,J=1.2and 8.4Hz),7.27(1H,m),7.39(1H,m).IR(CHCl3)3463,3033,3021,3014,2992,2924,2870,1708,1643,1597,1523,1488/cm.[α]D=+46.3°(MeOH,c=1.01,21℃).No.2a-121CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.14和1.23(每個(gè)3H,每個(gè)s),1.47-2.47(14H,m),3.95(3H,s),4.31(1H,m),5.32-5.50(2H,m),6.98(1H,dd,J=0.9和8.4Hz),7.09(1H,ddd,J=0.9,7.7和8.4Hz),7.45(1H,m),8.19(1H,dd,J=2.1和8.1Hz),8.32(1H,d,J=9.0Hz).IR(CHCl3)3400,3078,3028,3020,3007,2924,2870,2842,1736,1708,1640,1600,1536,1483,1470/cm.[α]D=+38.1°(MeOH,c=1.02,23℃).No.2a-122[α]D=+42.3°(MeOH,c=0.99,23℃).No.2a-123[α]D=+38.7°(MeOH,c=1.00,21℃).No.2a-124[α]D=+45.0°(MeOH,c=1.01,21℃).m.p.119.0-120.0℃No.2a-125[α]D=+49.8°(MeOH,c=1.01,22℃).No.2a-126CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.52-2.47(14H,m),4.26(1H,m),5.34-5.50(2H,m),6.22(1H,d,J=8.7Hz),7.55-7.61(4H,m).IR(CHCl3)3400,3078,3028,3020,3007,2924,2870,2842,1736,1708,1640,1600,1536,1483,1470/cm.[α]D=+63.0°(MeOH,c=1.01,23℃).No.2a-127CDCl3 300MHz0.91(1H,d,J=10.2Hz),1.10和1.20(每個(gè)3H,每個(gè)s),1.50-2.42(14H,m),4.23(1H,m),5.31-5.51(2H,m),6.45(1H,d,J=8.4Hz),7.01(1H,t,J=7.4Hz),7.22-7.27(2H,m),7.33-7.40(4H,m),7.53(2H,d,J=9.0Hz),8.30和8.48(每個(gè)1H,每個(gè)s)IR(CHCl3)3452,3028,3022,3015,2925,2870,1708,1654,1590,1514,1478/cm.[α]D=+59.5°(MeOH,c=1.01,23℃).No.2a-128d6-DMSO 300MHz0.84(1H,d,J=9.9Hz),1.06和1.19(每個(gè)3H,每個(gè)s),1.37-2.37(14H,m),3.79(1H,m),5.35-5.51(2H,m),6.08(1H,d,J=8.7Hz),6.85-6.90(1H,m),7.18-7.23(2H,m),7.35-7.38(2H,m),8.42(1H,s),12.00(1H,s).IR(Nujol)3395,3345,2925,2866,2623,2506,1697,1658,1638,1597,1557/cm.[α]D=+26.0°(MeOH,c=1.01,23℃).m.p.164.0-166.0℃No.2a-129CDCl3 300MHz1.01(1H,d,J=10.0Hz),1.17和1.25(每個(gè)3H,每個(gè)s),1.54-2.52(14H,m),4.34(1H,m),5.36-5.57(2H,m),6.42(1H,d,J=8.6Hz),7.51-7.60(2H,m),7.77(1H,dd,J=1.8和8.6Hz),7.85-7.96(3H,m),8.24(1H,brs).IR(CHCl3)3451,3060,3028,3010,2925,2870,1708,1652,1629,1600,1517,1502/cm.[α]D=+68.6°(MeOH,c=1.00,22℃).No,2a-130CDCl3 300MHz1.02(1H,d,J=10.2Hz),1.04和1.26(每個(gè)3H,每個(gè)s),1.54-2.52(14H,m),4.41(1H,m),5.41-5.58(2H,m),6.14(1H,d,J=9.0Hz),7.43-7.59(4H,m),7.85-7.92(2H,m),8.27(1H,dd,J=1.8和7.2Hz).IR(CHCl3)3436,3032,3010,2924,2870,2664,1708,1652,1512,1498/cm.[α]D=+93.9°(MeOH,c=1.00,22℃)m.p.94.0-96.0℃No.2a-131[α]D=+50.2°(MeOH,c=0.95,21℃).No.2a-132[α]D=+10.9°(MeOH,c=0.92,21℃).No.2a-133[α]D=+60.4°(MeOH,c=1.00,21℃).No.2a-134[α]D=+38.5°(MeOH,c=1.01,23℃).No.2a-135[α]D=+52.5°(MeOH,c=1.01,23℃).m.p.180.0-182.0℃No 2a-136[α]D=+35.3°(MeOH,c=1.02,23℃).m.p.79.0-80.0℃No.2a-137CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.22(每個(gè)3H,每個(gè)s),1.43(3H,t,J=6.9Hz),1.52-2.44(14H,m),4.03(2H,q,J=6.9Hz),4.26(1H,m),5.33-5.50(2H,m),6.19(1H,d,J=8.7Hz),6.88-7.00(6H,m),7.65-7.68(2H,m).IR(CHCl3)3455,3031,3024,3014,2988,2925,2870,1741,1708,1649,1602,1521,1504,1490/cm.[α]D=+52.0°(MeOH,c=1.01,23℃).No.2a-138CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.22(每個(gè)3H,每個(gè)s),1.35(6H,d,J=6.0Hz),1.53-2.46(14H,m),4.25(1H,m),4.51(1H,m),5.33-5.50(2H,m),6.12(1H,d,J=9.0Hz),6.87-6.99(6H,m),7.65-7.68(2H,m).IR(CHCl3)3454,3031,3014,2980,2925,2870,1741,1708,1649,1602,1522,1490/cm.[α]D=+50.0°(MeOH,c=1.05,22℃).No.2a-139CDCl3 300MHz1.00(1H,d,J=10.2Hz),1.16和1.24(每個(gè)3H,每個(gè)s),1.59-2.52(14H,m),4.31(1H,m),5.40-5.53(2H,m),6.36(1H,d,J=8.7Hz),6.70(1H,d,J=1.5Hz),7.12(1H,m),7.30(1H,m),7.47(1H,dd,J=0.6和 8.1Hz),7.61(1H,d,J=8.4Hz).IR(CHCl3)3449,3243,3029,3022,3013,2925,2871,1707,1631,1542,1505/cm.[α]D=+63.4°(MeOH,c=1.00,23℃).m.p.178.0-179.0℃No.2a-140CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.18和1.23(每個(gè)3H,每個(gè)s),1.57-2.50(14H,m),4.35(1H,m),5.32-5.55(2H,m),6.42(1H,d,J=8.7Hz),6.70(1H,d,J=1.5Hz),7.21-7.24(2H m),7.46(1H,m),7.76(1H,m),7.86(1H,d,J=3.0Hz),10.20(1H,s).IR(CHCl3)3465,3010,2924,1739,1604,1546,1504/cm.[α]D=+39.4°(MeOH,c=1.01,22℃).m.p.167.0-168.0℃No.2a-141CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.55-2.44(14H,m),3.84(3H,s),4.27(1H,m),5.34-5.52(2H,m),6.28(1H,d,J=9.0Hz),6.91和7.47(每個(gè)2H,每個(gè)d,J=9.0Hz),6.98和7.14(每個(gè)1H,每個(gè)d,J=16.5Hz),7.54和7.70(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3453,3025,3015,2925,2870,2839,1740,1708,1649,1602,1510,1493,1470/cm.[α]D=+73.4°(MeOH,c=1.02,22℃).m.p.155.0-157.0℃No.2a-142CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.52-2.45(14H,m),3.79(3H,s),4.27(1H,m),5.34-5.50(2H,m),6.24(1H,d,J=9.0Hz),6.49和6.62(每個(gè)1H每個(gè)d,J=12.3Hz),6.77和7.16(每個(gè)2H,每個(gè)d,J=8.7Hz),7.32和 7.59(每個(gè)2H,每個(gè)d,J=8.1Hz).IR(CHCl3)3453,3025,3014,2925,2870,2839,1739,1708,1649,1606,1510,1494/cm.[α]D=+60.7°(MeOH,c=0.99,22℃).No.2a-143[α]D=+57.3°(MeOH,c=1.01,23℃).No.2a-144[α]D=+12.2°(MeOH,c=1.00,23℃).m.p.114.0-116.0℃No.2a-145CDCl3 300MHz0.95(1H,d,J=10.2Hz),1.10和1.21(每個(gè)3H,每個(gè)s),1.52-2.44(14H,m),4.25(1H,m),5.33-5.49(2H,m),6.37(1H,d,J=8.7Hz),7.45-7.47(3H,m),7.62-7.66(2H,m),7.69和7.80(每個(gè)2H,每個(gè)d,J=7.5Hz,).IR(CHCl3)3449,3058,3027,3012,2925,2870,1708,1655,1513,1481,1043/cm.[α]D=+61.0°(MeOH,c=1.01,23℃).No.2a-146CDCl3 300MHz0.95(1H,d,J=10.5Hz),1.09和1.21(每個(gè)3H,每個(gè)s),1.50-2.41(14H,m),4.25(1H,m),5.33-5.49(2H,m),6.33(1H,d,J=8.4Hz),7.49-7.61(3H,m),7.91.7.92(2H,m),7.82和7.97(每個(gè)2H,每個(gè)d,J=8.7Hz,).IR(CHCl3)3447,3029,3023,3015,2925,2870,1708,1660,1514,1484,1321,1161/cm.[α]D=+62.0°(MeOH,c=1.00,22℃).No.2a-147CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),2.51(3H,s),4.26(1H,m),5.34-5.51(2H,m),6.23(1H,d,J=8.4Hz),7.26和7.64(每個(gè)2H,每個(gè)d,J=8.4Hz).IR(CHCl3)3453,3027,3015,2925,2870,2665,1708,1648,1596,1516,1484/cm.[α]D=+67.7°(MeOH,c=0.82,22℃).No.2a-148[α]D=+72.5°(MeOH,c=1.01,25℃).No.2a.149[α]D=+67.8°(MeOH,c=0.98,25℃).No.2a-150CDCl3 300MHz0.94(1H,d,J=10.2Hz),1.10和1.23(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.22(1H,m),5.36-5.55(2H,m),6.48(1H,d,J=8.4Hz),8.35(1H,s),8.90(1H,s).IR(CHCl3)3443,3374,3091,3024,3012,2925,2871,1709,1652,1525,1494/cm.[α]D=+58.1°(MeOH,c=1.01,23℃).m.p.120.0-122.0℃No.2a-151[α]D=+40.6°(MeOH,c=1.01,23℃).No.2a-152CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.10和1.24(每個(gè)3H,每個(gè)s),1.50-2.50(14H,m),2.71(3H,s),4.26(1H,m),5.37-5.51(2H,m),6.02(1H,d,J=9.0Hz),8.73(1H,s).IR(CHCl3)3463,3435,3087,3025,3014,2925,2870,1708,1649,1523,1503/cm.[α]D=+54.1°(MeOH,c=1.02,22℃).No.2a-153CDCl3 300MHz0.95(1H,d,J=9.9Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.50.2.50(14H,m),2.50(3H,s),4.26(1H,m),5.36-5.51(2H,m),6.01(1H,d,J=8.4Hz),6.88(1H,d,J=5.1Hz),7.26(1H,d,J=5.1Hz).IR(CHCl3)3469,3431,3025,3013,2925,2871,2664,1708,1639,1544,1505/cm.[α]D=+35.8°(MeOH,c=1.03,22℃).No.2a-154CDCl3 300MHz0.95(1H,d,J=9.9Hz),1.10和1.22(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),2.51(3H,d,J=1.2Hz),4.26(1H,m),5.34-5.50(2H,m),6.00(1H,d,J=8.4Hz),6.73(1H,dd,J=5.1和3.6Hz),7.29(1H,d,J=3.6Hz).IR(CHCl3)3450,3431,3026,3011,2925,2869,1739,1708,1639,1547,1508/cm.[α]D=+50.5°(MeOH,c=1.01,22℃).No.2a-155CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.19和1.25(每個(gè)3H,每個(gè)s),1.53-2.48(14H,m),4.31(1H,m),5.36-5.51(2H,m),6.79(1H,d,J=9.3Hz),7.29(1H,m),7.41(1H,m),7.48(1H,s),7.51(1H,m),7.66(1H,d,J=8.1Hz).IR(CHCl3)3436,3029,3024,3015,2925,2871,2670,1708,1659,1598,1510/cm.[α]D=+69.1°(MeOH,c=1.01,22℃).No.2a-156CDCl3∶CD3OD=10∶1 300MHz0.99(1H,d,J=9.9Hz),1.11和1.21(每個(gè)3H,每個(gè)s),1.56-2.58(14H,m),4.22(1H,m),5.35-5.59(2H,m),6.83(1H,d,J=8.4Hz),7.48(1H,d,J=8.4Hz),7.61(1H,dd,J=1.5和8.4Hz),8.09(1H,d,J=1.5Hz),8.12(1H,s).IR(KBr)3422,3 115,2985,2922,2869,2609,1708,1636,1578,1529,1470/cm.[α]D=+62.8°(MeOH,c=1.01,22℃).No.2a-157[α]D=+40.0°(MeOH,c=0.95,22℃).No.2a-158CDCl3 300MHz1.00(1H,d,J=10.5Hz),1.17和1.24(每個(gè)3H,每個(gè)s),1.54-2.50(14H,m),4.34(1H,m),5.36-5.52(2H,m),7.80(1H,d,J=9.0Hz),9.30(1H,s).IR(CHCl3)3410,3122,3030,3012,2925,2871,2668,1709,1667,1538,1466/cm.[α]D=+44.9°(MeOH,c=0.99,22℃).No.2a-159CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.13和1.22(每個(gè)3H,每個(gè)s),1.55-2.43(14H,m),3.03(6H,s),4.23(1H,m),5.32-5.51(2H,m),6.16(1H,d,J=8.7Hz),6.87和7.63(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3457,3028,3006,2924,2870,2654,1739,1709,1637,1608,1608,1534,1501/cm.[α]D=+64.8°(MeOH,c=1.01,22℃).No.2a-160d6-DMSO 300MHz0.83(1H,d,J=9.9Hz),1.02和1.19(每個(gè)3H,每個(gè)s),1.38-1.61(3H,m),1.90-2.32(11H,m),3.90(1H,m),5.41-5.44(2H,m),7.32(1H,dd,J=0.9和 7.2Hz),7.45-7.60(2H,m),7.77(1H,dd,J=0.9和7.8Hz),8.03(1H,d,J=6.9Hz),12.40(1H,s).IR(液蠟)3315,2924,2856,2656,2535,1737,1703,1637,1598,1581,1541/cm.[α]D=+78.5°(MeOH,c=1.01,24℃).m.p.161.0-162.0℃No.2a-161[α]D=+65.3°(MeOH,c=1.00,22℃).No.2a-162CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.13和1.25(每個(gè)3H,每個(gè)s),1.53-2.45(14H,m),4.30(1H,m),5.36-5.51(2H,m),6.32(1H,d,J=8.4Hz),7.88和8.28(每個(gè)2H,每個(gè)d,J=9.0Hz).IR(CHCl3)3448,3029,3016,2925,2870,1708,1664,1602,1527,1484,1347/cm.[α]D=+72.7°(MeOH,c=1.02,22℃).No.2a-163CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.55-2.51(14H,m),4.26(1H,m),5.36-5.57(2H,m),6.68(1H,d,J=7.8Hz),7.41(1H,dd,J=4.8和8.1Hz),8.20(1H,d,J=8.1Hz),8.66(1H,d,J=4.8Hz),9.00(1H,s).IR(CHCl3)3448,3026,3013,2925,2870,2534,1709,1658,1590,1515,1471/cm.[α]D=+71.3°(MeOH,c=1.01,22℃).No.2a-164[α]D=+40.8°(MeOH,c=0.98,22℃).No.2a-165CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.11和1.24(每個(gè)3H,每個(gè)s),1.55-2.52(14H,m),4.24(1H,m),5.37-5.57(2H,m),6.63(1H,d,J=7.8Hz),7.59和8.63(每個(gè)2H每個(gè)d,J=6.0Hz).IR(CHCl3)3447,3346,3028,3016,2925,2870,2538,1941,1708,1662,1556,1516/cm.[α]D=+75.4°(MeOH,c=1.01,22℃).No.2a-166CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.22(每個(gè)3H,每個(gè)s),1.51-2.44(14H,m),2.95(6H,s),4.25(1H,m),5.33-5.50(2H,m),6.19(1H,d,J=8.7Hz),6.77和6.97(每個(gè)2H,每個(gè)d,J=8.4Hz),6.94和7.65(每個(gè)2H,每個(gè)d,J=9.0Hz).IR(CHCl3)3453,3024,3016,2924,2871,2806,1739,1708,1647,1612,1604,1515,1490/cm.[α]D=+53.1°(MeOH,c=1.02,23℃).m.p.104.0-105.5℃No.2a-167CDCl3 300MHz1.01(1H,d,J=9.9Hz),1.19和1.26(每個(gè)3H,每個(gè)s),1.56-2.53(14H,m),4.37(1H,m),5.35-5.55(2H,m),6.47(1H,d,J=8.4Hz),7.61-7.71(2H,m),7.79(2H,s),7.89-7.97(2H,m),8.27(1H,d,J=2.1Hz),8.66-8.73(2H,m).IR(CHCl3)3450,3024,3014,2925,2870,2667,1707,1650,1531,1509/cm.[α]D=+70.5°(MeOH,c=1.00,22℃).No.2a-168CDCl3 300MHz1.02(1H,d,J=10.2Hz),1.20和1.26(每個(gè)3H,每個(gè)s),1.56-2.50(14H,m),4.38(1H,m),5.36-5.56(2H,m),6.51(1H,d,J=8.4Hz),7.61-7.93(7H,m),8.74(1H,d,J=8.4Hz),9.15(1H,s).IR(CHCl3)3517,3451,3060,3028,3011,2925,2870,2664,1709,1651,1519,1498/cm.[α]D=+54.4°(MeOH,c=1.00,23℃).No.2a-169CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.09和1.21(每個(gè)3H,每個(gè)s),1.50-2.44(14H,m),3.85(3H,s),4.24(1H,m),5.32-5.48(2H,m),6.19(1H,d,J=8.4Hz),6.94和7.45(每個(gè)2H,每個(gè)d,J=9.0Hz),7.11和7.45(每個(gè)2H,每個(gè)d,J=8.7Hz).IR(CHCl3)3516,3453,3029,3009,2925,2870,2840,2665,1708,1650,1593,1515,1493.1482/cm.[α]D=+57.8°(MeOH,c=1.00,23℃).No.2a-170CDCl3 300MHz0.98(1H,d,J=10.2Hz),1.15和1.24(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.28(1H,m),5.33-5.54(2H,m),6.25(1H,d,J=8.2Hz),7.38-7.44(2H,m),7.74(1H,s),7.81-7.86(2H,m).IR(CHCl3)3517,3448,3427,3024,3013,2925,2870,2669,1708,1650,1562,1535,1500/cm.[α]D=+61.6°(MeOH,c=1.00,23℃).No.2a-171CDCl3 300MHz0.96(1H,d,J=10.2Hz,1.11和1.22(每個(gè)3H,每個(gè)s),1.52-2.42(14H,m),2.48(3H,s),4.21(1H,m),5.31.5.52(2H,m),6.06(1H,d,J=8.2Hz),6.97和7.59(每個(gè)1H,每個(gè)d,J=1.2Hz).IR(CHCl3)3452,3113,3028,3007,2925,2870,2669,1708,1645,1554,1509/cm.[α]D=+52.4°(MeOH,c=1.00,23℃).No.2a-172CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.09和1.28(每個(gè)3H,每個(gè)s),1.50-2.40(14H,m),2.69(3H,s),4.24(1H,m),5.35-5.51(2H,m),5.96(1H,d,J=8.7Hz),7.03和7.07(每個(gè)1H,每個(gè)d,J=5.4Hz).IR(CHCl3)3451,3031,3013,2925,2870,2666,1708,1647,1542,1497/cm.[α]D=+51.2°(MeOH,c=1.00,23℃).No.2a-173CDCl3 300MHz0.95(1H,d,J=10.2Hz),1.10和1.23(每個(gè)3H,每個(gè)s),1.50-2.45(14H,m),4.22(1H,m),5.35-5.49(2H,m),6.05(1H,d,J=8.4Hz),7.26和7.75(每個(gè)1H,每個(gè)d,J=1.5Hz).IR(CHCl3)3451,3011,3029,3011,2925,2870,1708,1652,1538,1500/cm.[α]D=+50.6°(MeOH,c=1.01,23℃).No.2a-174CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.13和1.23(每個(gè)3H,每個(gè)s),1.52-2.50(14H,m),4.29(1H,m),5.35-5.51(2H,m),7.02(1H,d,J=8.4Hz),7.32和8.16(每個(gè)1H,每個(gè)d,J=3.9Hz).IR(CHCl3)3417,3115,3023,3014,2925,2870,1708,1645,1530/cm.[α]D=+48.8°(MeOH,c=1.02,23℃).No.2a-175CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.14和1.23(每個(gè)3H,每個(gè)s),1.50-2.52(14H,m),2.52(3H,s),4.29(1H,m),5.34-5.51(2H,m),7.78(1H,d,J=9.0Hz),7.24和7.52(每個(gè)1H,每個(gè)d,J=5.4Hz).IR(CHCl3)3329,3093,3023,3015,2924,2871,1708,1640,1526/cm.[α]D=+45.0°(MeOH,c=1.01,23℃).No.2a-176CDCl3 300MHz0.95(1H,d,J=10.5Hz),1.09和1.23(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),2.40(3H,d,J=0.9Hz),4.24(1H,m),5.35-5.51(2H,m),6.05(1H,d,J=8.7Hz),6.95(1H,m),7.57(1H,d,J=3.3Hz).IR(CHCl3)3517,3444,3103,3024,3013,2926,2870,1739,1708,1649,1636,1507/cm.[α]D=+54.8°(MeOH,c=1.01,23℃).m.p.97.0-99.0℃No.2a-177CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.52-2.45(14H,m),3.93(3H,s),4.27(1H,m),5.34-5.50(2H,m),6,35(1H,d,J=3.3Hz),7.80(1H,d,J=8.7Hz),8.10(1H,d,J=3.3Hz).IR(CHCl3)3395,3121,3031,3019,3012,2925,2871,1739,1709,1640,1557,1533/cm.[α]D=+22.8°(MeOH,c=1.01,23℃).m.p.109.0-112.0℃No.2a-178CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.10和1.23(每個(gè)3H,每個(gè)s),1.51-2.45(14H,m),4.24(1H,m),5.35-5.50(2H,m),6.09(1H,d,J=8.4Hz),7.17-7.31(6H,m),7.95(1H,d,J=1.5Hz).IR(CHCl3)3510,3451,3062,3031,3022,3011,2925,2870,2662,1708,1651,1582,1535.1497.1477/cm.[α]D=+47.9°(MeOH,c=1.01,25℃).No.2a-179CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.52-2.48(14H,m),4.30(1H,m),5.36-5.52(2H,m),6.73(1H,d,J=9.0Hz),6.26和7.37(每個(gè)1H,每個(gè)d,J=6.0Hz).IR(CHCl3)3509,3429,3115,3094,3025,3014,2925,2871,2666,1708,1649,1529,1510/cm.[α]D=+51.0°(MeOH,c=1.02,25℃).No.2a-180CDCl3 300MHz0.95(1H,d,J=10.2Hz),1.14和1.24(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),3.89(3H,s),4.21(1H,m),5.35-5.50(2H,m),6.05(1H,d,J=8.4Hz),6.46和7.04(每個(gè)1H,每個(gè)d,J=1.8Hz).IR(CHCl3)3516,3450,3114,3031,3010,2925,2871,1708,1648,1546,1511,1477/cm.[α]D=+49.1°(MeOH,c=1.01,25℃).No.2a-181CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.14和1.23(每個(gè)3H,每個(gè)s),1.52-2.48(14H,m),2.42(3H,s),4.31(1H,m),5.34-5.52(2H,m),8.07(1H,d,J=9.3Hz),7.27和8.17(每個(gè)1H,每個(gè)d,J=3.3Hz).IR(CHCl3)3510,3301,3112,3023,3007,2924,2871,2663,1708,1636,1534/cm.[α]D=+41.0°(MeOH,c=0.96,25℃).No.2a-182CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.53-2.46(14H,m),2.51(3H,s),4.21(1H,m),5.35-5.51(2H,m),6.05(1H,d,J=8.1Hz),7.26和7.78(每個(gè)1H,每個(gè)d,J=1.8Hz).IR(CHCl3)3509,3450,3109,3024,3012,2925,2870,2666,1708,1650,1535,1498.1471/cm.[α]D=+52.9°(MeOH,c=0.95,25℃).No.2a-183CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.12和1.22(每個(gè)3H,每個(gè)s),1.52-2.46(14H,m),4.25(1H,m),5.33-5.51(2H,m),6.17(1H,d,J=8.7Hz),7.01-7.05(3H,m).7.14和7.62(每個(gè)2H,每個(gè)d,J=8.7Hz),7.27-7.34(2H,m).IR(CHCl3)3428,3026,3015,2925,2870,2666,1739,1708,1643,1613,1594,1526,1499/cm.[α]D=+64.8°(MeOH,c=1.02,23℃).No.2a-184CDCl3 300MHz1.01(1H,d,J=10.2Hz),1.18和1.26(每個(gè)3H,每個(gè)s),1.55-2.50(14H,m),4.35(1H,m),5.35-5.55(2H,m),6.42(1H,d,J=8.7Hz),7.46-7.52(2H,m).7.73(1H,dd,J=1.8和8.4Hz),7.83-7.89(2H,m),8.21(1H,m),8.59(1H,d,J=1.5Hz).IR(CHCl3)3451,3031,3014,2925,2870,2660,1739,1708,1650,1604,1513,1463/cm.[α]D=+58.3°(MeOH,c=1.00,23℃).No.2a-185CDCl3 300MHz1.00(1H,d,J=10.2Hz),1.18和1.25(每個(gè)3H,每個(gè)s),1.55-2.50(14H,m),4.34(1H,m),5.35-5.54(2H,m),6.36(1H,d,J=8.7Hz),7.37(1H,t,J=7.4Hz),7.50(1H,m),7.57-7.59(2H,m),7.79(1H,dd,J=1.8和8.1Hz),7.99(1H,d,J=7.8Hz),8.39(1H,d,J=1.8Hz).IR(CHCl3)3451,3030,3020,2870,2665,1708,1652,1632,1603,1586,15 14,1469,1448/cm.[α]D=+59.4°(MeOH,c=1.0l,24℃).No.2a-186CDCl3 300MHz1.00(1H,d,J=10.5Hz),1.17和1.25(每個(gè)3H,每個(gè)s),1.54-2.50(14H,m),4.33(1H,m),5.35-5.54(2H,m),6.37(1H,d,J=8.7Hz),7.37(1H,t,J=7.4Hz),7.51(1H,t,J=7.8Hz),7.56(1H,m),7.70(1H,dd,J=1.2 and 8.4Hz),7.97(3H,m).IR(CHCl3)3451,3030,3014,2924,2870,2671,1739,1708,1652,1577,1517,1488,1471/cm.[α]D=+72.2°(MeOH,c=1.00,24℃).No.2a-187CDCl3 300MHz1.00(1H,d,J=9.8Hz),1.18和1.25(每個(gè)3H,每個(gè)s),1.54-2.53(14H,m),4.07(3H,s),4.37(1H,m),5.30-5.54(2H,m),7.34(1H,m),7.47(1H,s),7.47-7.60(2H,m),7.93(1H,d,J=7.8Hz),8.43(1H,s),8.49(1H,d,J=9.0Hz).IR(CHCl3)3397,3074,3027,3020,3009,2924,1738,1708,1647,1633,1534,1465,1453/cm.[α]D=+43.7°(MeOH,c=1.01,25℃).No.2a-188CDCl3 300MHz0.97(1H,d,J=10.2Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.53-2.50(14H,m),4.23(1H,m),5.37-5.50(2H,m),6.10(1H,d,J=9.0Hz),6.20(1H,m),6.51(1H,m),6.97(1H,m),10.81(1H,brs).IR(CHCl3)3450,3236,3112,3029,3015,2925,2871,2645,1701,1616,1558,1516/cm.[α]D=+50.6°(MeOH,c=1.01,24℃).No.2a-189CDCl3 300MHz0.94(1H,d,J=9.9Hz),1.11和1.23(每個(gè)3H,每個(gè)s),1.50-2.46(14H,m),3.93(3H,s),4.18(1H,m),5.35-5.52(2H,m),6.03(1H,d,J=9.3Hz),6.09(1H,m),6.48(1H,m),6.73(1H,m).IR(CHCl3)3452,3102,3028,3007,2925,2871,2666,1739,1708,1650,1536,1499,1471/cm.[α]D=+49.8°(MeOH,c=1.01,23℃).m.p.101.5-103.5℃No.2a-190CDCl3 300MHz0.94(1H,d,J=10.2Hz),1.11和1.21(每個(gè)3H,每個(gè)s),1.54-2.47(14H,m),4.23(1H,m),5.33-5.52(2H,m),6.06(1H,d,J=9.0Hz),6.34(1H,m),6.75(1H,m),6.36(1H,m),9.71(1H,brs).IR(CHCl3)3470,3215,3030,3020,3010,2925,2871,2664,1709,1613,1564,1510/cm.[α]D=+43.3°(MeOH,c=1.01,24℃).No.2a-191CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.11和1.22(每個(gè)3H,每個(gè)s),1.55-2.44(14H,m),3.66(3H,s),4.20(1H,m),5.35-5.51(2H,m),5.93(1H,d,J=8.4Hz),6.27(1H,dd,J=1.8and 2.7Hz),6.56(1H,t,J=2.7Hz),7.19(1H,t,J=1.8Hz).IR(CHCl3)3452,3031,3018,3006,2925,2871,2662,1736,1710,1634,1609,1556,1498/cm.[α]D=+43.1°(MeOH,c=1.01,23℃).No.2a-192CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.11和1.21(每個(gè)3H,每個(gè)s),1.43(3H,t,J=7.5Hz),1.54-2.44(14H,m),3.93(2H,q,J=7.5Hz),4.21(1H,m),5.33-5.51(2H,m),5.94(1H,d,J=8.4Hz),6.27(1H,dd,J=1.8和2.7Hz),6.62(1H,t,J=2.7Hz),7.26(1H,t,J=1.8Hz).IR(CHCl3)3630,3452,3032,3018,3006,2925,2871,2661,1735,1710,1633,1610,1555.1497/cm.[α]D=+40.1°(MeOH,c=1.00,23℃).No.2a-193CDCl3 300MHz0.95(1H,d,J=10.2Hz),1.10和1.22(每個(gè)3H,每個(gè)s),1.53-2.49(14H,m),2.58(3H,s),4.21(1H,m),5.35-5.54(2H,m),6.15(1H,d,J=8.1Hz),6.52(1H,dd,J=1.8和3.6Hz),7.29(1H,t,J=3.6Hz),7.94(1H,t,J=1.8Hz).IR(CHCl3)3516,3450,3410,3152,3027,3015,2925,2871,2670,1732,1648,1574,1509/cm.[α]D=+45.0°(MeOH,c=1.01,25℃).No.2a-194CDCl3 300MHz0.99(1H,d,J=10.2Hz),1.11和1.24(每個(gè)3H,每個(gè)s),1.52-2.53(14H,m),4.34(1H,m),5.33-5.57(2H,m),6.21(1H,d,J=8.6Hz),7.35-7.50(2H,m),7.83(1H,s),7.86(1H,m),.8.31(1H,m).IR(CHCl3)3443,3067,3013,2925,2870,2665,1708,1651,1515,1493/cm.[α]D=+55.7°(MeOH,c=1.01,23℃).No.2a-195CDCl3 300MHz1.01(1H,d,J=10.0Hz),1.06和1.26(每個(gè)3H,每個(gè)s),1.50-2.64(14H,m),2.68(3H,s),4.40(1H,m),5.36-5.61(2H,m),6.02(1H,d,J=9.4Hz),7.30-7.42(2H,m),7.73-7.86(2H,m).IR(CHCl3)3510,3434,3062,3029,3014,2924,2871,2669,1708,1650,1563,1539,1500/cm.[α]D=+72.4°(MeOH,c=1.00,23℃).m.p.111.0-112.0℃No.2a-196CDCl3 300MHz0.42和1.04(每個(gè)3H,每個(gè)s),0.80(1H,d,J=10.0Hz),1.11-2.48(14H,m),2.24(3H,s),4.02(1H,m),5.23-5.44(2H,m),5.53(1H,d,J=8.8Hz),7.27-7.31(2H,m),7.42-7.48(3H,m),7.93(1H,s).IR(CHCl3)3419,3114,3025,3006,2924,2871,2662,1737,1709,1636,1540,1519/cm.[α]D=+43.7°(MeOH,c=1.01,23℃).No.2a-197CDCl3 300MHz0.95(1H,d,J=10.0Hz),1.09和1.23(每個(gè)3H,每個(gè)s),1.54-2.46(18H,m),2.77(4H,brs),4.21(1H,m),5.32-5.54(2H,m),6.02(1H,d,J=8.6Hz),7.43(1H,s).IR(CHCl3)3445,3101,3024,3014,2928,2865,2661,1739,1708 1646,1550,1507/cm.[α]D=+51.9°(MeOH,c=1.01,23℃).No.2a-198CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.11和1.22(每個(gè)3H,每個(gè)s),1.50-2.44(14H,m),4.24(1H,m),4.42(2H,s),5.35-5.49(2H,m),6.25(1H,d,J=8.1Hz),7.33(1H,m),7.43(1H,dd,J=1.5和7.5Hz),7.49(1H,d,J=8.1Hz),7.60-7.63(1H,m),7.68(1H,dd,J=1.8和7.8Hz),8.02(1H,d,J=1.8Hz),8.19(1H,dd,J=1.5和8.1Hz).IR(CHCl3)3448,3030,3012,2925,2870,1739,1708,1671,1588,1559,1514,1472/cm.[α]D=+56.9°(MeOH,c=1.01,24℃).No.2a-199CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.11和1.22(每個(gè)3H,每個(gè)s),1.51-2.46(14H,m),3.40(1H,m),3.76(1H,m),4.24(1H,m),5.33-5.51(3H,m),6.25(1H,m),7.16(1H,m),7.24-7.33(2H,m),7.46(1H,d,J=7.5Hz),7.52-7.60(2H,m),7.85(1H,dd,J=1.8和4.5Hz).IR(CHCl3)3583,3447,3062,3028,3013,2924,2871,2663,1708,1651,1600,1557,1514.1471/cm.[α]D=+54.8°(MeOH,c=1.00,23℃).No.2a-200CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.12和1.23(每個(gè)3H,每個(gè)s),1.51-2.46(14H,m),4.25(1H,m),5.34-5.51(2H,m),6.25(1H,d,J=8.4Hz),7.02和7.10(每個(gè),1H,每個(gè)d,J=12.3Hz),7.23-7.33(4H,m),7.50(1H,m),7.64(1H,dd,J=1.8和7.8Hz),7.82(1H,d,J=1.8Hz).IR(CHCl3)3450,3060,3025,3014,2925,2871,2662,1708,1653,1596,1542,1513,1473/cm.[α]D=+62.5°(MeOH,c=1.00,24℃).No.2a-201CDCl3 300MHz0.95(1H,d,J=9.9Hz),1.15和1.22(每個(gè)3H,每個(gè)s),1.55-2.60(14H,m),4.26(1H,m),5.35-5.63(2H,m),7.14(1H,d,J=9.9Hz),7.34和7.40(每個(gè),1H,每個(gè)d,J=12.9Hz),7.62-7.73(4H,m),8.25-8.30(2H,m),8.72(1H,d,J=1.5Hz).IR(CHCl3)3443,3389,3297,3061,3030,3016,2925 2870,1726,1708 1652,1603,1521,1483,1472,1309/cm.[α]D=+61.1°(MeOH,c=1.01,23℃).No.2a-202CDCl3 300MHz0.96(1H,d,J=10.2Hz),1.09和1.22(每個(gè)3H,每個(gè)s),1.52-2.43(14H,m),2.63(3H,s),4.25(1H,m),5.33-5.49(2H,m),6.19(1H,d,J=8.4Hz),7.10和7.58(每個(gè)2H,每個(gè)d,J=9.0Hz),7.21(1H,m),7.30-7.32(2H,m),7.46(1H,d,J=7.5Hz)IR(CHCl3)3511,3453,3062,3032,3014,2925 2870,1739,1708,1650,1595,1556,1516,1482,1471/cm.[α]D=+60.2°(MeOH,c=1.01,25℃).No.2a-203CDCl3 300MHz0.96(1H,d,J=10.5Hz),1.09和1.23(每個(gè)3H,每個(gè)s),1.52-2.43(14H,m),4.23(1H,m),5.35-5.51(2H,m),5.93(1H,d,J=8.7Hz),6.56(1H,dd,J=0.9和1.8Hz),7.43(1H,t,J=1.8Hz),7.92(1H,dd,J=0.9和1.8Hz).IR(CHCl3)3517,3450,3134,3031,3008,2925,2870,2667,1708,1656,1588,1570,1514/cm.[α]D=+46.7°(MeOH,c=0.92,25℃).No.2b-1[α]D=+25.6°(MeOH,c=1.01,23℃).No.2b-2[α]D=+38.9°(MeOH,c=1.01,24℃).No.2c-1[α]D=+60.5°(MeOH,c=1.01,22℃).No.2c-2[α]D=+55,8°(MeOH,c=0.92,22℃).No.2c-3[α]D=+54,7°(MeOH,c=1.01,22℃).No.2d-1[α]D=-6.2°(MeOH,c=1.00,21℃).No.2d-2[α]D=+15.8°(MeOH,c=0.34,22℃).No.2d-3[α]D=+31.6°(MeOH,c=1.01,22℃).No.2e-1[α]D=-9.4°(MeOH,c=1.00,22℃).No.2e-2[α]D=-1.8°(MeOH,c=1.02,23℃).No.2e-3[α]D=-6.7°(MeOH,c=1.01,23℃).No.2f-1[α]D=+6.8°(MeOH,c=1.01,23℃).No.2f-2[α]D=-2.6°(MeOH,c=1.00,22℃).No.2f-3[α]D=-3.5°(MeOH,c==1.01,22℃).No.2g-1[α]D=+54,6°(MeOH,c=1.01,24℃).No.3a-2CDCl3 300MHz0.98-2.15(14H,m),2.31(2H,t,J=7.2Hz),2.35-2.40(1H,m),3.10-3.20(1H,m),5.00(1H,d,J=6.9Hz),5.30-5.48(2H,m),6.75(1H,d,J=10.2Hz),7.38-7.52(6H,m).IR(CDCl3)3266,3028,2954,2874,1709,1620,1448,1412,1318,1141,970,892/cm.[α]D=+20.3±0.6°(CHCl3,c=1.05,24℃).No.3a-3CDCl3 300MHz0.95-2.00(14H,m),2.20-2.29(3H,m),3.00-3.08(1H,m),3.66(3H,s),5.00(1H,d,J=6.6Hz),5.13-5.29(2H,m),7.38-7.52(3H,m),7.59-7.65(2H,m),7.69-7.75(2H,m),7.92-7.98(2H,m).IR(CHCl3)3376,3018,2946,2868,1727,1594,1436,1395,1322,1157,1095,890/cm.[α]D=+2.3±0.4°(CHCl3,c=1.03,22℃).mp.65-66.5℃No.3a-4CDCl3 300MHz0.93-2.05(14H,m),2.15-2.22(1H,m),2.31(2H,t,J=7.2Hz),3.01-3.10(1H,m),5.18-5.31(3H,m),7.38-7.52(3H,m),7.58-7.66(2H,m),7.69-7.76(2H,m),7.92-7.98(2H,m)IR(CHCl3)3374,3260,3020,2948,2868,1708,1594,1479,1396,1319,1156,1095,1052.891/cm.[α]D=+13.1±0.5°(CHCl3,c=1.16,24℃).No.3a.6CD3OD 300MHz1.04-1.95(14H,m),2.07(2H,t,J=7.8Hz),2.14-2.22(1H,m),2.94-3.00(1H,m),5.04-5.25(2H,m),7.36-7.52(3H,m),7.66-7.71(2H,m),7.78-7.85(2H,m),7.91-7.97(2H,m).IR(KBr)3421,3278,2951,2872,1562,1481,1409,1317,1156,1097,1057,895/cm[α]D=-15.3±0.5°(CHCl3,c=1.06,23℃).mp.105-112℃No.3a-11CDCl3 300MHz0.90-2.04(14H,m),2.08-2.19(1H,m),2.35(2H,t,J=7.2Hz),2.95-3.04(1H,m),5.17-5.32(3H,m),7.56-7.63(2H,m),7.83-7.95(2H,m).IR(CHCl3)3260,3020,2948,2868,1707,1569,1456,1383,1325,1268,1160,1088,1053.1006,892/cm.[α]D=+8.3±0.5°(CHCl3,c=1.00,22℃).No.3a-16CDCl3 300MHz0.80-1.90(14H,m),1.98-2.04(1H,m),2.27(2H,t,J=7.2Hz),2.88(6H,s),2.90-2.98(1H,m),4.88-5.00(2H,m),5.13(1H,d,J=7.2Hz),7.18(1H,d,J=7.5Hz),7.48-7.60(2H,m),8.25-8.33(2H,m),8.53(1H,d,J=8.7Hz).IR(CHCl3)3272,3020,2946,2866,2782,1708,1573,1455,1407,13 11,1229,1160,1142,1070,942,891/cm.[α]D=-19.7±0.6°(CHCl3,c=1.08,23.5℃).No.3a-31CDCl3 300MHz0.80-1.85(14H,m),2.02-2.08(1H,m),2.20(2H,t,J=7.2Hz),2.85-2.95(1H,m),3.68(3H,s),4.80.4.92(2H,m),4.96(1H,d,J=6.9Hz),7.50-7.70(3H,m),7.92-7.98(1H,m),8.07(1H,d,J=8.4Hz),8.29(1H,dd,J=1.5&7.5Hz),8.65(1H,d,J=8.7Hz).IR(CHCl3)3374,3016,2946,2868,1727,1506,1435,1318,1160,1133,1105,1051,984,890/cm.[α]D=-39.3±0.8°(CHCl3,c=1.07,22℃).No.3a-32CDCl3 300MHz0.80-1.90(14H,m),1.95-2.05(1H,m),2.27(2H,t,J=7.2Hz),2.90-2.96(1H,m),4.85-5.00(2H,m),5.23(1H,d,J=6.6Hz),7.50-7.72(3H,m),7.95(1H,d,J=8.1Hz),8.07(1H,d,J=8.4Hz),8.29(1H,dd,J=1.2&7.5Hz),8.66(1H,d,J=9.0Hz).IR(CHCl3)3270,3020,2948,2868,1708,1455,1412,1317,1159,1132,1104,1079,1051,983,89 1/cm.[α]D=-29.2±0.6°(CHCl3,c=1.08,22℃).No.3a-33CD3OD 300MHz0.94-1.84(14H,m),1.96-2.08(3H,m),2.77-2.84(1H,m),4.67-4.84(2H,m),7.55-7.75(3H,m),8.02(1H,d,J=7.8Hz),8.12-8.26(2H,m),8.74(1H,d,J=8.7Hz).IR(KBr)3432,3298,2951,2872,1564,1412,1315,1159,1134,1107,1082,1058,986/cm.[α]D=-79.9±1.2°(CH3OH,c=1.00,23℃).No.3a-34CDCl3 300MHz0.97-1.91(14H,m),2.13-2.20(1H,m),2.42(2H,t,J=7.2Hz),3.00-3.07(1H,m),5.06-5.24(2H,m),5.33(1H,d,J=6.9Hz),7.57-7.68(2H,m),7.82-8.00(4H,m),8.45(1H,d,J=1.2Hz)IR(CHCl3)3260,3020,2948,1708,1408,1319,1154,1129,1073,953,893/cm.[α]D=+20.7±0.6°(CHCl3,c=1.07,22℃).No.3a-35CD3OD 300MHz1.03-2.20(m,17H),2.97(m,1H),5.02(m,2H),7.64(m,2H),8.00(m,4H),8.43(S,1H).IR(KBr)3360,3285,1562,1407,1316,1153,1130,1075/cm.[α]D0[α]365=+20.9±0.6°(CH3OH,c=1.04,23℃).No.3d-1CDCl3 300MHz0.93-2.55(m,17H),3.02(m,1H),5.24(m,2H),6.48(m,1H),7.35-7.60(m,3H),7.85-8.00(m,2H)IR(液蠟)3275,1548,1160,1094,758,719,689,591,557/cm.[α]D=+19.0±0.6°(CH3OH,c=1.010,26.5℃).元素分析 (C20H26NO4S 1/2ca 1.0H2O)計(jì)算值C,57.94;H,6.82;N,3.38;Ca,4.83;H2O,4.35實(shí)測(cè)值C,57.80;H,6.68;N,3.68;Ca,5.06;H2O,4.50No.3d-6[α]D=-20.7±0.6°(CHCl3,c=1.00,24℃).No.3d-7[α]D=-3.2±0.4°(CHCl3c=1.03,22℃).mp.65-67℃No.3d-8[α]D=-14.5±0.5°(CHCl3,c=1.07,24℃).No.3d-9[α]D=+12.2±0.5°(CH3OH,c=1.00,23℃).mp.119-125℃No.3d-10[α]D=+39.7±0.8°(CHCl3,c=1.07,22℃).No.3d-11[α]D=+29.2±0.7°(CHCl3,c=1.06,22℃).No.3d-12[α]D=+76.4±1.1°(CH3OH,c=1.03,24℃).No.3d-14[α]D=-20.6±0.6°(CHCl3,c=1.07,22℃).No.3d-15[α]365=-28.0±0.7°(CH3OH,c=1.03,24.5℃).No.3d-16[α]D=-8.7±0.5°(CHCl3,c=1.06,22℃).No.3d-17CDCl3 300MHz0.80-2.15(m,24H),2.32(t,J=7Hz,2H),2.68(t,J=7Hz,2H),3.02(m,1H),2.15(m,24H),2.32(t,J=7Hz,2H),2.68(t,J=7Hz,2H),3.02(m,1H),5.22(m,2H),5.38(d,J=7Hz,1H),7.30(A2B2q-Apart,J=8Hz,2H),7.81(A2B2qBpart,J=8Hz,2H),9.86(brs,1H).[α]D0[α]365=-9.7±0.5°(CHCl3,c=1.03,22℃).No.3d-24[α]D=+19.2±0.6°(CHCl3,c=1.05,23℃).No.3d-26CD3OD 300MHz0.90-2.20(20H,m),2.88(1H,m),3.07(2H,q,J=7.0Hz),5.00-5.40(2H,m),7.20-7.60(4H,m),7.95(1H,m).IR(KBr)3415,3254,1698,1564,1314,1154/cm.No.3d-28CD3OD 300MHz0.90-2.20(20H,m),2.73(2H,q,J=7.0Hz),2.93(1H,m),5.00-5.30(2H,m),7.40-7.50(2H,m),7.60-7.77(2H,m).IR(KBr)3435,3280,1562,1323,1304,1151/cm.No.3d-30元素分析 (C20H25BrNO4SNa)計(jì)算值C50.21;H5.27;Br16.70;N2.93;S6.70;Na4.81實(shí)測(cè)值C50.22;H5.40;Br15.57;N2.88;S6.41;Na5.10IR(KBr)3425,3280,3085,1697,1570,1410,1321,1165,1155/cm.No.3e-1CD3OD 300MHz0.71(1H,d,J=10.2Hz),1.04(3H,s),1.12(3H,s),1.35-2.28(14H,m),2.42(3H,s),3.17-3.25(1H,m),5.18-5.39(2H,m),7.37(2H,d,J=8.4Hz),7.75(2H,d,J=8.4Hz).IR(CHCl3)3400,3289,2986,2924,2870,1559,1424,1322,1305,1160,1095,1075,1030/cm.[α]D=+25.9±0.7°(CH3OH,c=1.00,23℃).
以上實(shí)例中制備的化合物,按照以下實(shí)驗(yàn)例中所示的方法進(jìn)行活體和離體活性試驗(yàn)。
實(shí)驗(yàn)1與PGD2受體結(jié)合
材料與方法
(1)人體血小板膜級(jí)分的制備
血樣是用含有3.8%檸檬酸鈉的塑料注射器從健康志愿者(成年男性和女性)的靜脈抽取的,放入塑料試管中,用顛倒法緩緩混合。然后,該樣品以1800轉(zhuǎn)/分、在室溫離心分離10分鐘,收集含有PRP(富含血小板的血漿)的上清液。使PRP以2300轉(zhuǎn)/分在室溫再離心分離22分鐘,以得到血小板。這些血小板用一臺(tái)勻漿機(jī)(Ultra-Turrax)勻化,隨后以20,000轉(zhuǎn)/分在4℃離心分離10分鐘,得到血小板膜級(jí)分。在蛋白質(zhì)測(cè)定后,把這種膜級(jí)分調(diào)制成2mg/ml,在-80℃的電冰箱中保存直至使用。
(2)與PGD2受體結(jié)合
向結(jié)合反應(yīng)溶液(50mM Tris/HCl,pH 7.4,5mM MgCl2)(0.2ml)中添加人體血小板膜級(jí)分(0.1mg)和5nM[3H]PGD2(115Ci/mmol),在4℃反應(yīng)90分鐘。反應(yīng)完成后,反應(yīng)混合物通過(guò)玻璃纖維濾紙過(guò)濾,用冷卻的食鹽水洗滌若干次,測(cè)定該濾紙上截留的放射性。從總結(jié)合量中扣除非特異性結(jié)合(10μM PGD2存在下的結(jié)合),計(jì)算出特異性結(jié)合。每種化合物的結(jié)合抑制活性表達(dá)為50%抑制所需要的濃度(IC50),它是通過(guò)將每種化合物存在下的結(jié)合比(%)作圖繪制一條代換曲線來(lái)確定的,在這種情況下,試驗(yàn)化合物不存在時(shí)的結(jié)合比是100%。結(jié)果列于下表中。
化合物號(hào) 活性(μM) 化合物號(hào) 活性(μM)
3a-4 0.6 2a-4 0.54
1a-1158.6 2a-17 0.12
1a-28 0.0452a-21 5.2
1a-47 0.0086 2a-28 0.046
1a-1000.56 2a-95 1.6
1a-1760.0472a-1090.003
1a-2 0.13 1a-1620.027
實(shí)驗(yàn)2 用人體血小板評(píng)估對(duì)PGD2受體的拮抗活性
用一支事先添加了1/9體積的檸檬酸/右旋葡萄糖溶液的注射器,從健康的志愿者身上抽取末梢血液。使該注射器以180g離心分離10分鐘,以得到上清液(PRP富含血小板的血漿)。所得到的PRP用一種洗滌緩沖液洗滌3次,血小板數(shù)目用一臺(tái)微型細(xì)胞計(jì)數(shù)器計(jì)數(shù)。調(diào)節(jié)懸浮液,使之以最終濃度為5×108/ml含有血小板,在37℃溫?zé)?,然后?-異丁基-l-甲基黃嘌呤(0.5mM)預(yù)處理5分鐘。向該懸浮液中添加以各種不同濃度稀釋的試驗(yàn)化合物。10分鐘后,添加0.1~2.0μM PGD2以誘導(dǎo)反應(yīng),15分鐘后添加HCl以使反應(yīng)停止。血小板用一臺(tái)超聲勻漿機(jī)破壞。離心分離后,用放射試驗(yàn)法測(cè)定上清液中的cAMP。藥物的PGD2受體拮抗作用評(píng)估如下。在各個(gè)濃度測(cè)定因添加PGD2而增加的關(guān)于cAMP的抑制率,然后,計(jì)算50%抑制所需要的藥物濃度(IC50)。結(jié)果列于下表中。
化合物號(hào) 對(duì)人體血小板cAMP增加的抑制(IC50)(μM)
3a-16 0.37
1a-12 12.1l
1a-28 0.30
1a-47 2.09
2a-2 0.77
2a-4 0.94
2a-35 1.52
2a-75 0.71
實(shí)驗(yàn)3 利用鼻塞模型進(jìn)行的實(shí)驗(yàn)
以下描述利用豚鼠測(cè)定鼻腔阻力和評(píng)估抗鼻塞所用的方法。
一種l%卵白蛋白(OVA)溶液用超聲噴霧器處理,得到一種氣霧劑。Hartley雄性豚鼠以一周間隔吸入兩次該氣霧劑各10分鐘,使之敏化。敏化后7天,使該豚鼠暴露于一種抗原,以引發(fā)反應(yīng)。然后,在用戊巴比妥(30mg/kg,腹膜內(nèi))麻醉下將氣管切開(kāi),在肺側(cè)和鼻腔側(cè)各將套管插入氣管中。在肺側(cè)插入的管子與一個(gè)人工呼吸器連接,提供4ml空氣×60次/分鐘。在用Garamin(2mg/kg,經(jīng)靜脈內(nèi))阻止豚鼠的自發(fā)呼吸之后,用人工呼吸器以70次/分鐘的頻率和4ml空氣/次的流量率向口鼻部供給空氣,利用一個(gè)裝在支氣管上的傳感器測(cè)定充氣所需的大氣壓力。用該測(cè)定值作為鼻腔阻力的一個(gè)參數(shù)??乖┞妒峭ㄟ^(guò)在該呼吸器與鼻腔套管之間發(fā)生3分鐘3%0VA溶液的氣霧劑進(jìn)行的。試驗(yàn)藥物是在抗原暴露之前10分鐘經(jīng)靜脈內(nèi)注射的。連續(xù)測(cè)定0~30分鐘之間的鼻腔阻力,其效果表達(dá)為在30分鐘內(nèi)利用AUC對(duì)載體所得到的值的抑制率(縱軸為鼻腔阻力(cm H2O),橫軸為時(shí)間(0~30分鐘)),作為一種指示。結(jié)果列于下表中。化合物號(hào)抑制率(%)1mg/kg(經(jīng)靜脈內(nèi))備 注1a-28 441a-98 691a-100501a-115661a-116481a-120583mg/kg(經(jīng)靜脈內(nèi))1a-2 821a-162801a-176601a-267622a-4 602a-21 522a-28 542a-95 772a-96 7710mg/kg(經(jīng)口)2a-109732a-1106610mg/kg(經(jīng)口)22a-194 79
配方1 片劑的制備
以常用方式制備每片含有40mg有效成分的片劑。40mg片劑的組分如下(+)-(Z)-7-[(1R,2S,3S,4S)-3-苯磺酰胺基雙環(huán)[2.2.1]庚-2-基]-5-庚烯酸鈣·二水合物 40.0mg羥丙基纖維素 3.6mg硬脂酸鎂 0.4mg玉米淀粉18.0mg乳糖58.0mg
合計(jì)120.0mg
配方2顆粒劑的制備組分(+)-(Z)-7-[(1R,2S,3S,4S)-3-苯磺酰胺基雙環(huán)[2.2.1]庚-2-基]-5-庚烯酸鈣·二水合物 100.0mg羥丙基纖維素 30.0mg羧甲基纖維素鈣 30.0mg滑石粉 10.0mgPoloxamer 18820.0mg結(jié)晶纖維素 70.0mg玉米淀粉300.0mg乳糖440.0mg
合計(jì)1000.0mg
權(quán)利要求
1.一種PGD2拮抗劑,其中包含下面通式(I)的化合物或其鹽或其水合物作為活性成分
其中
是
或
A是亞烷基,任選地插入雜原子或亞苯基,含有氧代基,和/或有不飽和鍵;
B是氫、烷基、芳烷基或酰基;
R是COOR1,CH2OR2或CON(R3)R4;
R1是氫或烷基;
R2是氫或烷基;
R3和R4各自獨(dú)立地是氫、烷基、羥基或烷基磺?;?br>
X1是單鍵、亞苯基、亞萘基、噻吩二基、吲哚二基,或噁唑二基;
X2是單鍵、-N=N-,-N=CH-,-CH=N-,-CH=N-N-,-CH=N-O-,-C=NNHCSNH-,-C=NNHCONH-,-CH=CH-,-CH(OH)-,-C(Cl)=C(Cl)-,-(CH2)n-,亞乙炔基,-N(R5)-,-N(R51)CO-,-N(R52)SO2-,-N(R53)CON(R54)-,-CON(R55)-,-SO2N(R56)-,-O-,-S-,SO-,SO2-,-CO-、噁二唑二基、噻二唑二基或四唑二基;
X3是烷基、鏈烯基、炔基、芳基、芳烷基、雜環(huán)基、環(huán)烷基、環(huán)烯基、亞噻唑啉基甲基(thiazolinylidenemethyl)、亞噻唑烷基甲基(thiazolidinylidenemethyl)、-CH=NR6或-N=C(R7)R8;
R5、R51、R52、R53、R54、R55和R56各是氫或烷基;
R6是氫、烷基、羥基、烷氧基、氨基甲酰氧基、硫代氨基甲酰氧基、脲基或硫代脲基;
R7和R8各自獨(dú)立地是烷基、烷氧基或芳基;
n是1或2;
Z是-SO2-或-CO-;以及
m是0或1;
其中環(huán)狀取代基可以有1-3個(gè)選自下述的取代基硝基、烷氧基、氨磺酰、取代或未取代的氨基、酰基、酰氧基、羥基、鹵素、烷基、炔基、羧基、烷氧羰基、芳烷氧羰基、芳氧羰基、甲磺酰氧基、氰基、鏈烯氧基、羥烷基、三氟甲基、烷硫基、-N=PPh3、氧代、硫代、肟基、烷氧亞氨基、苯基和亞烷二氧基。
2.權(quán)利要求1的PGD2拮抗劑,其中活性成分是通式(I)的化合物,或其鹽或其水合物,其中
是
m是0;且當(dāng)Z是SO2時(shí),X1和X2兩者都是單鍵;X3是烷基、苯基、萘基、Stylyl(苯乙烯基)、喹啉基或噻吩基;以及這些取代基中環(huán)狀取代基可任選地帶有選自下述的1-3個(gè)取代基硝基、烷氧基、取代或未取代的氨基、鹵素、烷基和羥烷基。
3.權(quán)利要求l的PGD2拮抗劑,其中活性成分是通式(I)的化合物,或其鹽或其水合物,其中
是
當(dāng)m是1時(shí),X1和X2兩者都是單鍵;而X3是任選地被鹵素取代的苯基。
4.權(quán)利要求l的PGD2拮抗劑,其中活性成分是通式(I)的化合物,或其鹽或其水合物,其中
是
當(dāng)m是1時(shí),X1是苯基,X2是-CH2-或-N=N-,而X3是苯基。
5.權(quán)利要求1的PGD2的拮抗劑,它是一種用于治療鼻塞的藥物。
6.式(Ia)的化合物或其鹽或其水合物
其中A、B、R、X1、X2和X3的定義同上,其條件是其中(1)X1和X2是單鍵,而X3是取代或未取代的苯基,或萘基;以及(2)A是5-亞庚烯基,R是COOR1(R1是氫或甲基),X1是1,4-亞苯基,X2是單鍵,而X3是苯基的那些化合物除外。
7.權(quán)利要求6的化合物、其鹽或其水合物,其中X1和X2都是單鍵,X3是異噁唑基、噻二唑基、異噻唑基、嗎啉基、吲哚基、苯并呋喃基、二苯并呋喃基、二苯并二喔星基、苯并噻吩基、二苯并噻吩基、咔唑基、呫噸基、菲啶基、二苯并噁庚因基、二苯并硫雜七環(huán)基(thiepinyl)、肉啉基(cinnolyl)、苯并吡喃基(chromenyl)、苯并咪唑基或二氫苯并硫雜七環(huán)基(thiepinyl),A、B和R的定義同上。
8.權(quán)利要求6的化合物、其鹽或其水合物,其中X1是單鍵,X2是亞苯基,X3是鏈烯基、炔基、-CH=NR6或-N=C(R7)R8,而A、B、R、R6、R7和R8的定義同上。
9.權(quán)利要求6的化合物、其鹽或其水合物,其中R是COOR1,X1是亞苯基或噻吩二基,X2是單鍵、-N=N-、-CH=CH-、-CONH-、-NHCO-或亞乙炔基,而X3是苯基、亞噻唑啉基甲基、亞噻唑烷基甲基或噻吩基,而A、B、R1、R6、R7和R8的定義同上。
10.式(Ib)的化合物或其鹽或其水合物
其中
是
或
A、B、R、X1、X2和X3的定義同上,其條件是其中X1和X2是單鍵,而X3是苯基,以及其中X1是單鍵,X2是-O-,而X3是芐基的那些化合物除外。
11.權(quán)利要求10的化合物、其鹽或其水合物,其中
是
而A、B、R、X1、X2和X3的定義同上。
12.權(quán)利要求11的化合物、其鹽或其水合物,其中R是COOR1(R1的定義同上)。
13.權(quán)利要求11的化合物、其鹽或其水合物,其中X1是亞苯基或噻吩二基,X2是單鍵、-N=N-、-CH=CH-、亞乙炔基、-O-、-S-、-CO-、-CON(R55)-(R55的定義同上)、-N(R51)CO-(R51的定義同上),而X3是苯基或噻吩基。
14.權(quán)利要求10的化合物、其鹽或其水合物,其中
是
而A、B、R、X1、X2、X3和Z的定義同上。
15.權(quán)利要求14的化合物、其鹽或其水合物,其中B是氫,X1和X2兩者都是單鍵,X3是噻吩基、噻唑基、噻二唑基、異噻唑基、吡咯基、吡啶基、苯并呋喃基、苯并咪唑基、苯并噻吩基、二苯并呋喃基、二苯并噻吩基、喹啉基或吲哚基。
16.權(quán)利要求15的化合物、其鹽或其水合物,其中X1是亞苯基、噻吩二基、吲哚二基或噁唑二基,X2是單鍵、-N=N-、-CH=CH-、亞乙炔基、-S-或-O-,而X3是芳基或雜環(huán)基。
全文摘要
通式(Ⅰ)的化合物、其鹽或其水合物,其中(a)代表(b)或(c),例如化合物(d)和(e),這些可用作PGD2拮抗劑,因而可用于(例如)全身性肥大細(xì)胞沉積病或全身性肥大細(xì)胞活化失調(diào)的治療,支氣管收縮藥,抗哮喘藥,變應(yīng)性鼻炎劑藥物,變應(yīng)性結(jié)膜炎藥物,蕁麻疹藥物,局部缺血性回流失調(diào)的治療,和抗炎劑。它尤其可用于治療鼻塞。
文檔編號(hào)C07D313/14GK1193315SQ9619632
公開(kāi)日1998年9月16日 申請(qǐng)日期1996年6月19日 優(yōu)先權(quán)日1995年6月21日
發(fā)明者大谷光昭, 有村昭典, 釣達(dá)男, 岸野淳二, 本摩恒利 申請(qǐng)人:鹽野義制藥株式會(huì)社