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Enzymatic desymmetrising redox reactions for the asymmetric synthesis of biaryl atropisomers.

ABSTRACT: Atropisomeric biaryls carrying ortho-hydroxymethyl and formyl groups were made enantioselectively by desymmetrisation of dialdehyde or diol substrates. The oxidation of the symmetrical diol substrates was achieved using a variant of galactose oxidase (GOase), and the reduction of the dialdehydes using a panel of ketoreductases. Either M or P enantiomers of the products could be formed, with absolute configurations assigned by time-dependent DFT calculations of circular dichroism spectra. The differing selectivities observed with different biaryl structures offer an insight into the detailed structure of the active site of the GOase enzyme.

SUBMITTER: Staniland S

PROVIDER: S-EPMC4497317 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Enzymatic desymmetrising redox reactions for the asymmetric synthesis of biaryl atropisomers.

Staniland Samantha S Yuan Bo B Giménez-Agulló Nelson N Marcelli Tommaso T Willies Simon C SC Grainger Damian M DM Turner Nicholas J NJ Clayden Jonathan J

Chemistry (Weinheim an der Bergstrasse, Germany) 20140822 41

Atropisomeric biaryls carrying ortho-hydroxymethyl and formyl groups were made enantioselectively by desymmetrisation of dialdehyde or diol substrates. The oxidation of the symmetrical diol substrates was achieved using a variant of galactose oxidase (GOase), and the reduction of the dialdehydes using a panel of ketoreductases. Either M or P enantiomers of the products could be formed, with absolute configurations assigned by time-dependent DFT calculations of circular dichroism spectra. The dif ...[more]

PMID: 25156181

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