Enzymatic Chemoselective Aldehyde-Ketone Cross-Couplings through the Polarity Reversal of Methylacetoin.
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.
Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy).|Departamento de Biotecnología, Universidad Politécnica Salesiana, Campus El Vecino, Calle Vieja 12-30 y Elia Liut, Cuenca (Ecuador).
Giovanni
G
Bernacchia
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy).
Olga
O
Bortolini
Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy).
Morena
M
De Bastiani
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy).
Lindomar Alberto
LA
Lerin
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany).
Sabrina
S
Loschonsky
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy).
Alessandro
A
Massi
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstrasse 25, 79104 Freiburg (Germany).
Michael
M
Müller
Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy). pierpaolo.giovannini@unife.it.
Pier Paolo
PP
Giovannini
D000438:Alcohols / Q000737:chemistry / Q000378:metabolism; D000447:Aldehydes / Q000737:chemistry*; D001407:Bacillus / Q000201:enzymology; D055162:Biocatalysis; D004926:Escherichia coli / Q000378:metabolism; D007659:Ketones / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013237:Stereoisomerism
D000438:Alcohols; D000447:Aldehydes; D007659:Ketones; D011994:Recombinant Proteins; D010088:Oxidoreductases
asymmetric synthesis; enzyme catalysis; oxidoreductases; tertiary alcohols; thiamine diphosphate