Synthesis of Branched-Chain Sugars with a DHAP-Dependent Aldolase: Ketones are Electrophile Substrates of Rhamnulose-1-phosphate Aldolases

Angew Chem Int Ed Engl. 2018 May 4;57(19):5467-5471. doi: 10.1002/anie.201712851. Epub 2018 Mar 30.

Abstract

Dihydroxyacetone phosphate (DHAP)-dependent rhamnulose aldolases display an unprecedented versatility for ketones as electrophile substrates. We selected and characterized a rhamnulose aldolase from Bacteroides thetaiotaomicron (RhuABthet) to provide a proof of concept. DHAP was added as a nucleophile to several α-hydroxylated ketones used as electrophiles. This aldol addition was stereoselective and produced branched-chain monosaccharide adducts with a tertiary alcohol moiety. Several aldols were readily obtained in good to excellent yields (from 76 to 95 %). These results contradict the general view that aldehydes are the only electrophile substrates for DHAP-dependent aldolases and provide a new C-C bond-forming enzyme for stereoselective synthesis of tertiary alcohols.

Keywords: aldolases; biocatalysis; branched-chain sugars; carboligation; tertiary alcohols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde-Lyases / chemistry
  • Aldehyde-Lyases / metabolism*
  • Bacteroides thetaiotaomicron / enzymology
  • Dihydroxyacetone Phosphate / chemistry
  • Dihydroxyacetone Phosphate / metabolism*
  • Ketones / chemistry
  • Ketones / metabolism*
  • Molecular Structure
  • Stereoisomerism
  • Substrate Specificity
  • Sugars / chemistry
  • Sugars / metabolism*

Substances

  • Ketones
  • Sugars
  • Dihydroxyacetone Phosphate
  • Aldehyde-Lyases
  • rhamnulose-1-phosphate adolase