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

Date

2013-07-31

Author

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

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

142
views

0
downloads

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.

Subject Keywords

Physical and Theoretical Chemistry, Inorganic Chemistry, Organic Chemistry, Catalysis

URI

https://hdl.handle.net/11511/41975

Journal

TETRAHEDRON-ASYMMETRY

DOI

https://doi.org/10.1016/j.tetasy.2013.05.023

Collections

Department of Chemistry, Article

Suggestions

OpenMETU
Core

Asymmetric synthesis of novel 1,4-aminoalcohol ligands with norbornene and norbornane backbone: use in the asymmetric diethylzinc addition to benzaldehyde Tanyeli, Cihangir; ERDEM, Mine; ÇAKIR, Esen; KESKİN, Eda (Elsevier BV, 2007-09-27) The asymmetric synthesis of cis-1,4-aminoalcohols with norbornene and norbornane backbone was performed starting with (2S, 3R)-(-)-cis-hemiester 1 (98% ee). Chemoselective amination with HMPTA followed by Grignard reactions and subsequent LAH reductions afforded compounds 5a-d. cis-Hemiester 1 was also transformed into chiral ligands 7a-f and 9a-d with the DCC coupling method followed by LAH reduction using acyclic, heterocyclic amines and various aniline derivatives and p-toluenesulfonamide, respectively. ...
Asymmetric synthesis of 1,4-amino alcohol ligands with a norbornene backbone for use in the asymmetric diethylzinc addition to benzaldehyde Tanyeli, Cihangir (Elsevier BV, 2005-06-06) The asymmetric synthesis of cis-1,4-amino alcohols with a norbornene backbone was performed starting with (2S,3R)(-)-cis-hemiester 2 (98% ee). Chemoselective amination with NH4OH and HMPTA followed by LAH reduction afforded 5 and 7. respectively. Amido ester 6 was transformed into chiral ligand 9 with Grignard reaction followed by LAH reduction. The chiral ligands 5. 7. and 9 were subjected to asymmetric diethylzinc addition to examine their effectiveness as chiral catalysts. Among these, c chiral ligand 7 ...
Enantioselective synthesis of 2-(2-arylcyclopropyl)glycines: Conformationally restricted homophenylalanine analogs Demir, Ayhan Sıtkı; Sesenoglu, O; Ulku, D; Arici, C (Wiley, 2004-01-01) Starting from simple aromatic aldehydes and acetylfuran, (E)-1-(furan-2-yl)-3-arylprop-2-en-1-ones (2) were synthesized in high yields. Cyclopropanation of the C=C bond with trimethylsulfoxonium iodide (Me3SO+I-) furnished (furan-2-yl)(2-arylcyclopropyl)methanones 3 in 90-97% yields. Selective conversion of cyclopropyl ketones to their (E)- and (Z)-oxime ethers 5 and oxazaborolidine-catalyzed stercoselective reduction of the C-N bond followed by separation of the formed diastereoisomers, furnished (2-arylcy...
Enantioselective synthesis of both enantiomers of 2-amino-2-(2-furyl)ethan-1-ol as a flexible building block for the preparation of serine and azasugars Demir, Ayhan Sıtkı; Sesenoglu, O; Aksoy-Cam, H; Kaya, H; Aydogan, K (Elsevier BV, 2003-05-16) The selective conversion of 1-(2-furyl)-2-hydroxyethan-1-one and ethyl 2-(2-furyl)-2-oxo acetate into (E)- and (Z)-oximes and oxime ethers followed by oxazaborolidine-catalyzed enantioselective reduction using different amino alcohols furnished both enantiomers of the important chiral building block 2-amino-2-(2-furyl)ethan-1-ol with an ee of up to 96%.
A new and efficient chemoenzymatic route to both enantiomers of alpha '-acetoxy-alpha-methyl and gamma-hydroxy-alpha-methyl cyclic enones Demir, Ayhan Sıtkı; Findik, H; Kose, E (Elsevier BV, 2004-03-08) A chemoenzymatic synthesis of both enantiomers of the pharmacologically interesting alpha'-acetoxy-alpha-methyl and gamma-hydroxy-alpha-methyl cyclic enones starting from alpha-methyl-beta-methoxy cyclic enones is reported. Manganese(Ill) acetate-mediated acetoxylation followed by the enzyme-mediated hydrolysis of alpha'-acetoxy enone provides acetoxy enones 1a and 2a and hydroxy enones 1b and 2b with high enantiomeric excesses in good yields. The reduction of the acetoxy and hydroxy enones furnished both e...

Citation Formats

S. Ayan et al., “Asymmetric synthesis and molecular docking study of enantiomerically pure pyrrolidine derivatives with potential antithrombin activity,” TETRAHEDRON-ASYMMETRY, pp. 838–843, 2013, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41975.