Results
Title

Enzymatic Chemoselective Aldehyde-Ketone Cross-Couplings through the Polarity Reversal of Methylacetoin.

Authors

Bernacchia, Giovanni; Bortolini, Olga; De Bastiani, Morena; Lerin, Lindomar Alberto; Loschonsky, Sabrina; Massi, Alessandro; Müller, Michael; Giovannini, Pier Paolo

Abstract

The thiamine diphosphate (ThDP) dependent enzyme acetoin:dichlorophenolindophenol oxidoreductase (Ao:DCPIP OR) from Bacillus licheniformis was cloned and overexpressed in Escherichia coli. The recombinant enzyme shared close similarities with the acetylacetoin synthase (AAS) partially purified from Bacillus licheniformis suggesting that they could be the same enzyme. The product scope of the recombinant Ao:DCPIP OR was expanded to chiral tertiary α-hydroxy ketones through the rare aldehyde-ketone cross-carboligation reaction. Unprecedented is the use of methylacetoin as the acetyl anion donor in combination with a range of strongly to weakly activated ketones. In some cases, Ao:DCPIP OR produced the desired tertiary alcohols with stereochemistry opposite to that obtained with other ThDP-dependent enzymes. The combination of methylacetoin as acyl anion synthon and novel ThDP-dependent enzymes considerably expands the available range of CC bond formations in asymmetric synthesis.

Subjects

THIAMIN pyrophosphate; CHEMOSELECTIVITY; KETONES; BACILLUS licheniformis; ASYMMETRIC synthesis

Publication

Angewandte Chemie, 2015, Vol 127, Issue 24, p7277

ISSN

0044-8249

Publication type

Academic Journal

DOI

10.1002/ange.201502102