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

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

doi:10.1002/anie.201502102

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

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

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	7171-7175
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	54
Issue number	24
DOIs	https://doi.org/10.1002/anie.201502102
State	Published - 1 Jun 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Keywords

asymmetric synthesis
enzyme catalysis
oxidoreductases
tertiary alcohols
thiamine diphosphate

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title = "Enzymatic Chemoselective Aldehyde-Ketone Cross-Couplings through the Polarity Reversal of Methylacetoin",

abstract = "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.",

keywords = "asymmetric synthesis, enzyme catalysis, oxidoreductases, tertiary alcohols, thiamine diphosphate",

author = "Giovanni Bernacchia and Olga Bortolini and {De Bastiani}, Morena and Lerin, {Lindomar Alberto} and Sabrina Loschonsky and Alessandro Massi and Michael M{\"u}ller and Giovannini, {Pier Paolo}",

note = "Publisher Copyright: {\textcopyright} 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",

year = "2015",

month = jun,

day = "1",

doi = "10.1002/anie.201502102",

language = "English",

volume = "54",

pages = "7171--7175",

journal = "Angewandte Chemie - International Edition",

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T1 - Enzymatic Chemoselective Aldehyde-Ketone Cross-Couplings through the Polarity Reversal of Methylacetoin

AU - Bernacchia, Giovanni

AU - Bortolini, Olga

AU - De Bastiani, Morena

AU - Lerin, Lindomar Alberto

AU - Loschonsky, Sabrina

AU - Massi, Alessandro

AU - Müller, Michael

AU - Giovannini, Pier Paolo

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

KW - asymmetric synthesis

KW - enzyme catalysis

KW - oxidoreductases

KW - tertiary alcohols

KW - thiamine diphosphate

UR - http://www.scopus.com/inward/record.url?scp=84930624489&partnerID=8YFLogxK

U2 - 10.1002/anie.201502102

DO - 10.1002/anie.201502102

M3 - Article

C2 - 25914187

AN - SCOPUS:84930624489

SN - 1433-7851

VL - 54

SP - 7171

EP - 7175

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 24

ER -

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

Abstract

Bibliographical note

Keywords

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