Novel fungal metabolites as cell wall active antifungals: Fermentation, isolation, physico-chemical properties, structure and biological activity

Two novel antifungal compounds, 1 (SCH466457), and 2 (SCH 466456 ), active in a "cell wall" assay, were isolated from the fermentation broth of an uni dentified fungus. The active compounds were separated from the broth filtra te by adsorption on a macroreticular resin and were purified on reverse pha se HPLC. Detailed mass spectrometric and NMR experiments and degradative st udies helped in elucidating the structures of these compounds. The compound s were identified to be peptides containing amino acids such as alanine, am inoisobutyric acid proline, leucine, valine, glycine and a previously ident ified beta -keto acid, 2-methyl 3-oxotetradecanoic acid.(5)) Both compounds were active against Cundida, dermatophytes and Aspergillus (Geometric Mean MIC's, 8.9, 20 and 16 mug/ml, and 64, 128 and 23 mug/ml respectively for 1 and 2).