光学活性3-(1′-羟基乙基)-4-乙酰氧基-β-内酰胺的立体选择性合成  

Asymmetric Synthesis of the Optically Active 3-(1′-Hydroxyethyl)-4-acetoxy-β-lactam

作　　者：胡键[1] 吴彤[2] 李恒光[2] 谢如刚[1] 甘亚[2] 吕丁[2] 

机构地区：[1]四川大学化学系,成都610064 [2]四川抗菌素工业研究所,成都610051

出　　处：《化学学报》2001年第2期279-283,共5页Acta Chimica Sinica

基　　金：国家新药研究开发基金 ( 96-90 1-0 5 -81)资助项目

摘　　要：(1′R ,3R ,4R) -N -取代 - 3 - ( 1′ -羟基乙基 ) - 4-乙酰氧基 - β -内酰胺 ( 3 )是合成青霉烯和碳青霉烯类β -内酰胺抗生素的关键中间体 .以廉价的L -抗坏血酸为原料 ,制得S -缩异丙氧叉甘油醛 ( 5 ) ,与胺反应定量转变成相应的手性亚胺 ( 6a～ 6d) ,6与双烯酮 [2 + 2 ]环加成反应 ,高立体选择性地合成 3 (S) -乙酰基 - β -内酰胺 ( 8a～ 8d) ,其非对映体过量由类似反应的 80 %提高到接近 10 0 % .8a经四步反应得到目标化合物銻,3R,4R)-N-substituted-3-(1′-hydroxyethyl)-4-acetoxy-β-lactams(3), a key intermediate for synthesis of the bapenem and carbapenem, has been efficiently synthesized using inexpensive L-ascorbic acid(4) as the chiral reagent. (S)-glyceraldehyde acetonide(5) was prepared conveniently by three steps from 4, and condensed with amines to give the chiral imines(6). The -cycloaddition of diketene with the chiral imines(6) underwent in a highly stereoselective manner to give a series of 3(S)-acetyl-β-lactams(8). The target compound 3a was then obtained through further reactions from 8a.

关 键 词：N-取代-3-(1'-羟基乙基)-4-乙酰氧基-β-内酰胺 [2+2]环加成反应 L-抗坏血酸 立体选择性合成 抗生素 

分 类 号：TQ465[化学工程—制药化工]