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Enzymatic Chemoselective Aldehyde–Ketone Cross‐Couplings through the Polarity Reversal of Methylacetoin |
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| Authors: | Dr Giovanni Bernacchia Prof Olga Bortolini Dr Morena De Bastiani Dr Lindomar Alberto Lerin Dr Sabrina Loschonsky Prof Alessandro Massi Prof Dr Michael Müller Dr Pier Paolo Giovannini |
| Institution: | 1. Dipartimento di Scienze della Vita e Biotecnologie, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy);2. Departamento de Biotecnología, Universidad Politécnica Salesiana, Campus El Vecino, Calle Vieja 12‐30 y Elia Liut, Cuenca (Ecuador);3. Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via L. Borsari, 46, 44121 Ferrara (Italy);4. Institute of Pharmaceutical Sciences, Albert‐Ludwigs‐Universit?t Freiburg, Albertstrasse 25, 79104 Freiburg (Germany) |
| 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. |
| Keywords: | asymmetric synthesis enzyme catalysis oxidoreductases tertiary alcohols thiamine diphosphate |