Bioreduction of alpha-Acetoxymethyl Enones: Proposal for an S(N)2 ' Mechanism Catalyzed by Enereductase

Author(s)

Paula, Bruno R. S. ; Zampieri, Davila ; Rodrigues, J. Augusto R. ; Morana, Paulo J. S.

• Document type: Journal article
• Source: ADVANCED SYNTHESIS & CATALYSIS; v. 358, n. 22, p. 17-pg., 2016-11-17.

Abstract

(Z)-3-Acetoxymethyl-4-R-3-buten-2-ones (R= aryl, alkyl) and (Z)-3-methyl-4-R-3-buten-2-ones (R= aryl) were synthesized and submitted to reduction by the yeast Saccharomyces cerevisiae producing the (R)-and (S)-4-R-3-methybutan-2-ones, respectively. This stereochemistry control strategy was applied in the syntheses of (R)-and (S)-Tropional U with moderate to high enantiomeric excesses. Other (Z)-3-acyloxymethyl-4-phenyl-3-buten-2-ones showed similar behavior to the (Z)-3-acetoxymethyl counterpart, and the acylated Morita-Baylis-Hillman adduct 1-acetoxy-2-methylene-1-phenylbutan-3-one produced a mixture of products, with and without the acetoxy group, via three different reaction path-ways. In addition to experiments employing whole cells, those in which isolated enereductases were used suggested that the main pathway through which the loss of the acetoxy group occurs during the biocatalytic cascade is an S(N)2'-type reaction, rather than formal hydrogen addition followed by acetic acid elimination. Finally, related ethyl enones were reduced enantioselectively by the yeast Candida albicans, producing both (R)-and (S)-reduction products, depending on the presence of the acetoxy group in the starting material. (AU)

• FAPESP's process: 12/08385-6 - Study of enzymatic reductions of alpha,beta-unsaturated ketones, and their applications in the preparation of compounds of synthetic interest
• Grantee: Bruno Ricardo Silva de Paula
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/00108-9 - Application of biocatalysis in organic synthesis using whole cells of microorganisms
• Grantee: José Augusto Rosário Rodrigues
• Support Opportunities: Regular Research Grants