Synthesis of new polyoxin derivatives and their activity against chitin synthase from Candida albicans

Two analogues of L-alanylpolyoxin C with a modified peptide bond were synthesized and tested for inhibition of chitin synthase in Candida albicans. N-Methylation of the peptide bond (compound 13) or the replacement of it by NH2CH2 (compound 9) led to loss of activity in the enzyme assay. A novel analogue (compound 5) of nikkomycin was synthesized from uracil polyoxin C and (2S,3R)-3-hydroxyhomotyrosine, a component of echinocandin C. Despite high activity in the chitin synthase assay, 5 had no inhibitory effect on cells of C. albicans.