高等学校化学学报

高等学校化学学报 ›› 2002, Vol. 23 ›› Issue (6): 1060.

• 研究论文 • 上一篇    下一篇

d-生物素的不对称全合成研究(Ⅴ)

陈芬儿, 傅晗, 孟歌, 罗有富, 鄢明国   

  1. 复旦大学化学系, 上海 200433
  • 收稿日期:2001-02-21 出版日期:2002-06-24 发布日期:2002-06-24
  • 通讯作者: 陈芬儿(1959年出生),男,博士,教授,博士生导师,从事药物合成和不对称合成研究.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)资助

Studies on the Asymmetric Total Synthesis of d-Biotin(Ⅴ)

CHEN Fen-Er, FU Han, MENG Ge, LUO You-Fu, YAN Ming-Guo   

  1. Department of Chemistry, Fudan University, Shanghai 200433, China
  • Received:2001-02-21 Online:2002-06-24 Published:2002-06-24

PDF (PC)

被引次数

33

摘要： 以二异丁基氢化铝使(3aS,6aR)-1,3-二苄基-四氢-4H-噻吩并[3,4-d]-咪唑-2,4(1H)-二酮(1)高立体选择性地还原成(3aS,4S,6aR)-1,3-二苄基-4-羟基-四氢-1H-噻吩并[3,4-d]-咪唑-2(3H)-酮(2),再经缩合,Witting烯化成(3aS,6aR)-1,3-二苄基-四氢-1H-噻吩并[3,4-d]咪唑-2(3)-酮-4-烯戊酸(4),后者经催化氢转移还原、脱苄即得d-生物素,以化合物1计算总产率为42%.

关键词: d-生物素, 维生素H, 立体选择性还原, 催化氢转移, 不对称合成

Abstract: An efficient, high yielding and stereoselective synthesis of d biotin(6) is described. The stereoselective reduction of the known(3a S, 6a R)-1,3-dibenzyl tetrahydro 4Hthieno imidazol-2,4(1H)-dione(1) with diisobutylaluminum hydride(DIBAL-H) in toluene gave(3a S, 4 S, 6a R)-1,3 dibenzyl-4-hydroxy tetrahydro 1Hthieno imidazol-2(3H)-one(2) in 91% yield with 99.7% e.e.. Alcohol 2 was directly converted into(3a S, 4 S, 6a R) phosphonium salt 3 upon reaction with triphenylphosphine hydrogen tetrafluoroborate. Condensation of the corresponding ylide with 4 formylbutric acid afforded unsaturated acid 4. Catalytic hydrogen transfer hydrogenation of compound 4 with Pd D297 resin/ammonium formate system led stereoselectively to(3a S, 4 S, 6a S)-dibenzylbiotion(5), which was debenzylated by treatment with orthophospaoric acid in the presence of phenol to yield d biotin(6). The overall yield of d biotin was 42% from thiolactone 1.

Key words: d Biotin, Vitamin H, Steroselective reduction, Catalytic hydrogen transfer, Asymmetric synthesis

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