高等学校化学学报 ›› 2001, Vol. 22 ›› Issue (7): 1141.

• 研究论文 • 上一篇    下一篇

d-生物素的不对称全合成研究(Ⅱ)

陈芬儿, 凌秀红, 吕银祥, 张晓跃, 彭晓华   

  1. 复旦大学化学系, 上海 200433
  • 收稿日期:2000-06-02 出版日期:2001-07-24 发布日期:2001-07-24
  • 通讯作者: 陈芬儿(1959年出生),男,教授,博士生导师,从事药物合成化学和不对称合成研究.E-mail:rfchen@fudan.edu.cn E-mail:rfchen@fudan.edu.cn
  • 基金资助:

    化学工业部科技发展计划项目(批准号:96107)

Studies on the Asymmetry Total Synthesis of d-Biotin(Ⅱ)

CHEN Fen-Er, LING Xiu-Hong, LÜ Yin-Xiang, ZHANG Xiao-Yue, PENG Xiao-Hua   

  1. Department of Chemistry, Fudan University, Shanghai 200433, China
  • Received:2000-06-02 Online:2001-07-24 Published:2001-07-24

摘要: 1,3-二苄基咪唑啉-2-酮-顺-4,5-二羧酸经脱水、单酯化,拆分成(4S,5R)-顺-1,3-二苄基-5-甲氧基羰基-2-氧代咪唑啉-4-羧酸,再经还原环合,硫代成(3aS,6aR)-1,3-二苄基-四氢-4H-噻吩并[3,4-d]咪唑-2,4(1H NMR)-二酮(7),后者经格氏反应、脱水、还原、裂解环合一锅合成(3aR,8aS,8bS)-1,3-二苄基-2-氧代-十氢咪唑[3,4-d]噻吩并[1,2-a]锍溴化物(11),继而经缩合、开环、水解、脱羧、脱苄而得d-生物素(1),总收率为14.5%.

关键词: d-生物素, 维生素H, (1S, 2S)-(+)-苏式-1-(对硝基苯基)-2-氨基-1, 3-丙二醇, 催化氢转移, 非对映异构体结晶分析, 相转移催化, 全合成

Abstract: An efficient and practical total synthesis of d-biotin is described.(4S,5R )-cis-1,3-dibenzyl-5-methoxycarbonyl-2-oxo-imidazoline-4-carboxylic acid, prepared from 1,3-dibenzylimidazolidone-2-cis-4,5-dicarboxylic acid via dehydration, monoesterification, optical resolution was subjected to reduction cyclization, sulfuration to produce (3aS,6aR )-1,3-dibenzyl tetrahydro 4-Hthienoimidazol-2, 4(1H NMR) dione(7). Compound 7 via Grignard reaction, dehydration, reduction, cleavage cyclization in one pot procedure led to (3aR, 8aS, 8bS )-1,3-dibenzyl-2-oxo-decahydromidazo thienothiolium bromide(11), which was converted to d-biotin via condensation, ring opening, hydrolysis, decarboxylation, debenzylation in an overall yield of 14.5%.

Key words: d-Biotin, Vitamin H, (1 S,2 S)-(+)-threo-1-(p-Nitrophenyl)-2-amino-1,3-propanediol, Catalytic hydrogen transfer, Diastereoisomeric crystallization resolution, Total asymmetry synthesis, Chase transfer catalysis

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