A CONVENIENT DEGRADATION OF POLYOXIN D TO URACIL POLYOXIN-C - ACCESS TO KEY INTERMEDIATES AND SYNTHESIS OF ANTIFUNGAL ALPHA-AMINOACYL DERIVATIVES OF UPOC

A convenient degradation of readily available polyoxin D under Edman conditions gave carboxyuracil polyoxin C 3 in high yield. Decarboxylation to uracil polyoxin C 5 (UPOC) and ring contraction to imidazolone compound 8, gave important nikkomycin Z and X intermediates respectively. Syntheses of new polyoxin/nikkomycin analogs 12-27, some with excellent chitin synthetase inhibition and Candida albicans whole cell activity are described. The importance of beta-methyl substituted amino acid side chains for whole cell activity is highlighted.