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

2013-07-31
Ayan, Seylan
Doğan, Özdemir
Ivantcova, Polina M.
Datsuk, Nikita G.
Shulga, Dmitry A.
Chupakhin, Vladimir I.
Zabolotnev, Dmitry V.
Kudryavtsev, Konstantin V.
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.