(1R,2S,3R,4S,6R)-2,3,4-三羟基-2-(苄氧羰基氨基)-环己烷甲酸苄酯的高立体选择性合成  

Highly Stereoselective Synthesis of(1R,2S,3R,4S,6R)-2,3,4-Trihydroxy-cyclohexyl-β-amino Acid Derivative

作　　者：张茜[1] 梁希[1] 张金钟[1] 陈安齐[1] 

机构地区：[1]厦门大学化学化工学院化学系,福建厦门361005

出　　处：《厦门大学学报（自然科学版）》2007年第6期804-807,共4页Journal of Xiamen University：Natural Science

基　　金：国家自然科学基金(20372056)资助

摘　　要：多羟基环己基手性β-氨基酸及其衍生物具有重要的药物、生物和合成用途.本文对从内消旋cis-1,2,3,6-四氢邻苯二甲酸酐经去对称化得到的内酯关键中间体(2)的绝对构型进行了确定,并通过邻二羟基化和内酯开环,经两步反应以45%的产率从化合物(2)高立体选择性地合成了光学活性的(1R,2S,3R,4S,6R)-2,3,4-三羟基-2-(苄氧羰基氨基)-环己烷甲酸苄酯(6).Polyhydroxy cyclohexyl-fl-amino acids and their derivatives have important pharmaceutical, biological and synthetic applications. This paper describes the determination of the absolute configuration of the key lactone intermediate （2） ,obtained by cin- chonine mediated desymmetrization of cis-1,2,3,6-tetrahydrophthalic anhydride （1）, and its application in the stereoselective synthesis of a polyhydroxy cyclohexyl-β-amino acid derivative （6）. In order to determine the absolute stereochemistry of the lactone intermediate, compound （2）was treated with K2 CO2 in benzyl alcohol to provide the ring opened product （3） which was converted to its C4 p-bromobenzoate （4） whose absolute stereochemistry was determined as（1S,4S, 6R） by single crystal X-ray diffraction analysis therefore proved the configuration of the lactone intermediate （2）. Catalytic dihydroxylation of the lactone intermediate （2） with OsO4 and NMO provided the desired dihydroxy compound （5） which underwent alcoholisms with benzyl alcohol in the presence of K2CO2 ,providing the target compound,（1R,2S,3R,4S,6R）-2,3,4-trihydroxy-cyclohexyl-β-amino acid derivatives （6）,in 2 steps in 45 % overall yield in a highly stereoselective manner, which highlighted the usefulness of the lactone intermediate （2） in the asymmetric synthesis of polyhydroxy cyclohexyl-β-amino acid derivatives.

关 键 词：多羟基环己基-β-氨基酸 催化邻二羟基化 立体选择性合成 绝对构型 

分 类 号：O621.16[理学—有机化学]