Synthesis of a Carbohydrate-Derived Hydroxamic Acid Inhibitor of the Bacterial Enzyme (LpxC) Involved in Lipid A Biosynthesis

Abstract

[reaction: see text] The enzyme LpxC (UDP-3-O-[(R)-3-hydroxymyristoyl]-GlcNAc deacetylase) catalyzes the second step of lipid A biosynthesis and is essential for bacterial growth. A GlcNAc-derived hydroxamic acid inhibitor 8 of this enzyme was synthesized using two different routes. Compound 8 exhibits activity toward LpxC enzymes from a wider spectrum of bacterial species than any of the previously reported hydroxamic acid inhibitors.