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

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.