Synthesis of Oxazinyl Analogues of Fosmidomycin Using RCM Methodology

Abstract

Fosmidomycin is a promising antimalarial compound with a novel mode of action, the inhibition of 1-deoxy- D-xylulose 5-phosphate reductoisomerase, a key enzyme in the biosynthesis of isoprenoids through the nonmevalonate pathway. This paper describes the synthesis of a series of analogues in which the hydroxamate moiety is incorporated in a ring structure, leaving the complexation with the enzyme up to the oxygen lone pairs instead of the free hydroxyl group. The antimalarial activities of the different analogues are currently under investigation.