Contribution to the synthesis of aureobasidin A. Synthesis of cyclopeptolides containing the sequence leucyl‐N‐methyl‐β‐hydroxyvalyl‐ (2R)‐oxy‐(3R)‐methyl‐pentanoic acid *

The efficient antimycotic agent aureobasidin A, isolated from the culture broth of Aureobasidium pullulans R 106, and the [(R)-Pro9]-aureobasidin A were prepared starting from benzyl N-Boc-N-methyl-(S)-beta-triethylsiloxyvalinate, the synthesis of which is described here. The easy accessibility of the tripeptolide benzyl Boc-leucyl-N-methyl-beta-hydroxyvalyl-(2R)-oxy-(3R)-methylpentanoa te [Boc-Leu-HOMeVal-(R)-HMP-OBn] facilitates the construction of the cyclopeptolides 28, 34, 45 and 47. The peptide bonds of the N-methylamino acids were formed with the help of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophophate. The rings of [(R)-Pro9]-aureobasidin A and of cyclopeptolides 28, 34, 45 and 47 were closed by way of pentafluorophenyl esters. The ring of aureobasidin A could only be formed with bromo-tris-pyrrolidinophosphonium hexafluorophosphate.