Chemoenzymatic synthesis of differentially protected 3-deoxysugars.
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.
Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland.
Dennis G
DG
Gillingham
Pierre
P
Stallforth
Alexander
A
Adibekian
Peter H
PH
Seeberger
Donald
D
Hilvert
D055162:Biocatalysis; D002241:Carbohydrates / Q000096:biosynthesis* / Q000737:chemistry*; D020134:Catalytic Domain; D008958:Models, Molecular; D009097:Multienzyme Complexes / Q000737:chemistry / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D002241:Carbohydrates; D009097:Multienzyme Complexes; D011773:Pyruvates; C408144:macrophomate synthase