Synthesis of oxazinyl analogues of fosmidomycin using RCM methodology

摘要

Fosmidomycin is a promising antimalarial compound with a novel mode of action. It inhibits 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a key enzyme in the biosynthesis of isoprenoids through the nonmevalonate pathway present in malaria parasites. This study describes the synthesis of a series of analogues in which the hydroxamate moiety is incorporated in a ring structure, so complexation with the enzyme could occur via the oxygen lone pairs instead of the free hydroxyl group. The antimalarial activities of the different analogues are currently under investigation.