Chemoenzymatic synthesis of differentially protected 3-deoxysugars

Nat Chem. 2010 Feb;2(2):102-5. doi: 10.1038/nchem.504. Epub 2010 Jan 17.

Abstract

3-Deoxysugars are important constituents of complex carbohydrates. For example, 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) is an essential component of lipopolysaccharides in Gram-negative bacteria, 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN) is widely found in carbohydrates of the bacterial cell wall and in lower vertebrates, and sialic acid is a common cap of mammalian glycoproteins. Although ready access to such sugars would benefit the creation of vaccine candidates, antibiotics and small-molecule drugs, their chemical synthesis is difficult. Here we present a simple chemoenzymatic method for preparing differentially protected 3-deoxysugar derivatives from readily available starting materials. It exploits the promiscuous aldolase activity of the enzyme macrophomate synthase (MPS) to add pyruvate enolate diastereoselectively to a wide range of structurally complex aldehydes. A short synthesis of KDN illustrates the utility of this approach. Enzyme promiscuity, which putatively fosters large functional leaps in natural evolution, has great promise as a source of synthetically useful catalytic transformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Carbohydrates / biosynthesis*
  • Carbohydrates / chemistry*
  • Catalytic Domain
  • Models, Molecular
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism*
  • Pyruvates / metabolism
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Carbohydrates
  • Multienzyme Complexes
  • Pyruvates
  • macrophomate synthase

Associated data

  • PubChem-Substance/85845735
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