New Routes to Chiral Evans Auxiliaries by Enzymatic Desymmetrisation and Resolution Strategies

Abstract

This paper describes how enantiomerically enriched Evans auxiliaries can be successfully prepared by either an enzymatic desymmetrisation strategy or an asymmetric synthesis using racemic auxiliaries and an enzymatic resolution. Desymmetrisation of N-Boc-protected serinol has been achieved in good yield and high enantiomeric excess using porcine pancreas lipase. This has been exploited in different ways to prepare enantiomerically enriched (4R)-and (4S)-substituted 2-oxazolidinones. In another approach to asymmetric synthesis, starting from a racemic Evans auxiliary, by means of a diastereoselective aldol reaction coupled with a lipase-catalysed resolution, we achieved the preparation of enantiomerically enriched b-hydroxy acids and enantiomerically enriched 2-oxazolidinones.

Enantioselective Enzymatic Desymmetrizations in Organic Synthesis

“…Although they fulfill all the criteria required from a good auxiliary, their application can be limited by the availability of an appropriate enantiomerically pure amino acid or alcohol. Williams and co-workers have successfully developed the synthesis of both enantiomers of the Evans auxiliary 4-hydroxymethyl-1,3-oxazolidin-2-one by means of a route that makes use of an enzymatic desymmetrization of N -BOC-protected serinol ( 4 ) (Scheme ). After optimization of reaction conditions ( R )-(−)-3- O -acetyl-2- N -( tert -butoxycarbonyl)serinol [( R )- 5 ] was obtained enantiopure and in high yield when PPL was used as catalyst in vinyl acetate.…”

Synthesis and characterization of peptidomimetics containing oxazolidin-2-one and oxazolidine scaffolds

“…Several studies have exploited β-amino alcohols cyclization, especially for the synthesis of oxazolidinones. [25][26][27][28] In the first part of this article, we describe an application of this method to the synthesis of conformational constrained dipeptide mimetic from derivatives containing serine fragment. Thus, the cyclization was performed directly on the dipeptide resulting from peptide coupling with different amino acids: Val, Leu, Phe and aminocaproic acid.…”

Reverse Stereoselectivity in the Lipase‐Catalyzed Hydrolysis of Diacetylated Pyrimidine Acyclonucleosides

“…They catalyze the acyl group transfer process from the corresponding donor to the acceptor,w hich allows esterification, transesterification, and diol, amide, and peptide synthesis as well as ester,amide, and peptidehydrolysis. [3] Generally,l ipases display the same prochiral selectivity for the acylation of symmetrical diols and for the hydrolysis of the corresponding diesters. As ar esult, the products of the opposite absolute stereochemistry may be obtained by using the same enzyme.…”