Author: ["Dennis G. Gillingham","Pierre Stallforth","Alexander Adibekian","Peter H. Seeberger","Donald Hilvert"]
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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. Ready access to sugars in which the various hydroxyl groups are differentially protected will be of benefit in the production of vaccines, antibiotics and drugs. Here, a chemoenzymatic method that provides a direct route to such protected sugars is described.Cite this article
Gillingham, D., Stallforth, P., Adibekian, A. et al. Chemoenzymatic synthesis of differentially protected 3-deoxysugars. Nature Chem 2, 102–105 (2010). https://doi.org/10.1038/nchem.504 