高等学校化学学报 ›› 2000, Vol. 21 ›› Issue (3): 391.

• 论文 • 上一篇    下一篇

维生素B12环B酰亚胺前体及琥珀胺类药物不对称合成的研究

王恒山, 贾强, 杨晓武, 王锐   

  1. 兰州大学生命科学学院, 应用有机化学国家重点实验室, 兰州 730000
  • 收稿日期:1999-04-12 出版日期:2000-03-24 发布日期:2000-03-24
  • 通讯作者: 王 锐(1963年出生),男,博士,教授,博士生导师,从事不对称合成及多肽化学生物学研究.
  • 基金资助:

    国家自然科学基金(批准号:29972016);霍英东教育基金;教育部优秀青年教师基金;博士点基金;甘肃省自然科学基金资助

Studies on the Asymmetric Synthesis of Precursor of Vitamin B12 Ring-B Imide and Succinimide Drugs

WANG Heng-Shan, JIA Qiang, YANG Xiao-Wu, WANG Rui   

  1. School of Life Sciences, State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Landzhou 730000, China
  • Received:1999-04-12 Online:2000-03-24 Published:2000-03-24

摘要: 从γ-丁内酯合成了维生素B12环B酰亚胺前体及琥珀酰胺类药物的3个衍生物,进行了其中不对称季碳的构筑,改进了TiCl3还原硝基乙烯类化合物的反应,同时发现了一个简便合成乙琥酰胺环的新方法.

关键词: 不对称季碳, 维生素B12, 环B酰亚胺, 乙琥胺

Abstract: From γ-butyrolactone 1, we synthesized (S)-2-methyl-2-nitroethenyl butyrolactone (S)-3 by the mean of direct enantioselective construction of molecule with quaternary carbon stereocenter on the bases of our previous research. (S)-3 was obtained in36% overall yield with 94% optical purity. We established a set of conversions from(±)-3 to the precursor of Vitamin B12 ring Bimide 8 under mild conditions and complete the synthesis of three derivatives of ethosuximide 6_ 8 at the same time. By remolding TiCl3 reduction of nitroolefins the yield of 2-methyl butyrolactone-2-acetaldehyde 4 from 3 can be increased to 88%. Anew method has been found to directly construct succinimide ring from 2-methyl butyrolactone-3-acetic acid 5. The procedure of this conversion is DCCcondensation of 5 and dry benzylamine in acetonitrile catalyzed by DMAPat 0 ℃ over night.

Key words: Chiral quaternary carbon, Vitamin B12 ring-B imide, Succinimide

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