Synthesis and Precursor-Directed Biosynthesis of New Hormaomycin Analogues

Several new analogues of hormaomycin (1), a peptide lactone with interesting biological activities, were prepared by total synthesis or by precursor-directed biosynthesis. The new analogues 2a–c, 3a–c, O-MOM-1 and epi-O-MOM-1 as well as the model acyl tripeptides 20a–c and 21a–e were tested for their antibiotic activities to give new insights into structure–activity relationships of this class of compounds. In this context, an unexpected activity of 2c against C. albicans was discovered. The precursors necessary for feeding experiments, the amino acids 14a, 14b and 17, were prepared in 31, 48 and 55 % yield over 4 and 3 steps, respectively. In addition, these studies provided some new information about the biosynthetic route to furnish compound 1. They also support the notion that the combination of chemical and biological methods may provide a broad range of analogues of an interesting biologically active natural product. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)