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Enzymatic Chemoselective Aldehyde–Ketone Cross‐Couplings through the Polarity Reversal of Methylacetoin
Author(s) -
Bernacchia Giovanni,
Bortolini Olga,
De Bastiani Morena,
Lerin Lindomar Alberto,
Loschonsky Sabrina,
Massi Alessandro,
Müller Michael,
Giovannini Pier Paolo
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201502102
Subject(s) - ketone , aldehyde , chemistry , enzyme , stereochemistry , bacillus subtilis , oxidoreductase , cofactor , aldehyde reductase , atp synthase , biochemistry , organic chemistry , catalysis , reductase , bacteria , biology , genetics
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 CC bond formations in asymmetric synthesis.