Asymmetric synthesis and molecular docking study of enantiomerically pure pyrrolidine derivatives with potential antithrombin activity

Ayan S., DOĞAN Ö., Ivantcova P. M., Datsuk N. G., Shulga D. A., Chupakhin V. I., ...More

TETRAHEDRON-ASYMMETRY, vol.24, pp.838-843, 2013 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 24
  • Publication Date: 2013
  • Doi Number: 10.1016/j.tetasy.2013.05.023
  • Journal Name: TETRAHEDRON-ASYMMETRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.838-843
  • Middle East Technical University Affiliated: Yes

Abstract

The (2R,4R,5S)- and (2S,4S,5R)-enantiomers of 4-(tert-butyl) 2-methyl 5-(4-bromophenyl)-pyrrolidine-2,4-dicarboxylate 3 were synthesized efficiently with an ee of >90% on a gram scale using a FAM-catalytic methodology. Subsequent modification afforded enantiopure N-((4-chlorophenyl)thio)acetyl pyrrolidine derivatives 4, which are potential thrombin inhibitors according to comprehensive molecular docking studies. (C) 2013 Elsevier Ltd. All rights reserved.