Stereoselective syntheses of both the natural (C5′-S) and unnatural (C5′-R) diastereoisomers of uracil polyoxin C methyl ester have been developed. The key stereocontrolled step involves nucleophilic addition of tnmethylsilyl cyanide to the appropriate chiral sulfinimine derived from 2′,3′-protected 5′-formyluridine and (S)-(-)-tert-butanesulfinamide or (R)-(±)-tert-butanesulfinamide, respectively. A variety of substrate mimics designed to function as inhibitors of chitin synthase have been synthesized by conjugation of the methyl ester of uracil polyoxin C (UPOC) with activated isoxazole carboxylic acids. Amide bond formation was accomplished via coupling of the amino functionality of UPOC methyl ester with a free isoxazole acid using HBTU or alternatively an isoxazole pentafluorophenyl ester. The substrate mimics incorporate features of the nucleoside-peptide antibiotics, the polyoxins and the nikkomycins, as well as features of the transition state structure expected during polymerization of the natural chitin synthase substrate uridine diphosphoryl-N-acetylglucosamine (UDP-GIcNAc), namely, a metal-binding site and glycosyl oxocarbenium ion mimic. [ABSTRACT FROM AUTHOR]