An Alternative Formal Synthesis of (S)-(+)-Vigabatrin

Sudhir P. Chaskar; Ramchandra Honparkhe; Arvind K. Aghao; Rakesh G. Thorat; Chinmoy Pramanik

doi:10.1055/s-0042-1751470

Synthesis, Table of Contents

Synthesis 2024; 56(04): 549-552
DOI: 10.1055/s-0042-1751470

special topic

Synthetic Development of Key Intermediates and Active Pharmaceutical Ingredients (APIs)

An Alternative Formal Synthesis of (S)-(+)-Vigabatrin

Sudhir P. Chaskar

^aAPI R & D Centre, Emcure Pharmaceuticals Ltd., ITBT Park, Phase-II, MIDC, Hinjewadi, Pune-411057, Maharashtra, India

,

Ramchandra Honparkhe

^aAPI R & D Centre, Emcure Pharmaceuticals Ltd., ITBT Park, Phase-II, MIDC, Hinjewadi, Pune-411057, Maharashtra, India

,

Arvind K. Aghao

^bBelbhim College, Department of Chemistry, Beed, Maharashtra, India

,

Rakesh G. Thorat ∗

^aAPI R & D Centre, Emcure Pharmaceuticals Ltd., ITBT Park, Phase-II, MIDC, Hinjewadi, Pune-411057, Maharashtra, India

,

Chinmoy Pramanik

^aAPI R & D Centre, Emcure Pharmaceuticals Ltd., ITBT Park, Phase-II, MIDC, Hinjewadi, Pune-411057, Maharashtra, India

› Author Affiliations

Abstract

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Abstract

An improved synthesis of chirally pure advanced pyrrolidone intermediate of the (S)-(+)-vigabatrin, an antiseizure active pharmaceutical ingredient (API) is reported. The synthesis is developed using commercially available, cheaper amino acid (R)-methionine. Meldrum’s acid served as a two-carbon homologation unit to access the pyrrolidone intermediate in a short synthetic sequence. The sequence to pyrrolidone intermediate is scalable and eludes the use of organometallic pyrophoric reagents on a large scale.

Key words

GABA - vigabatrin - decarboxylative cyclization - Meldrum’s acid - seizure - API

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References

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