AMINO-ACIDS AND PEPTIDES, PART-104 - CONTRIBUTION TO THE SYNTHESIS OFAUREOBASIDIN-A - SYNTHESIS OF CYCLOPEPTOLIDES CONTAINING THE SEQUENCEL-BETA-HYDROXYVALYL-(2R)-OXY-(3R)-METHYL-PENTANOIC ACID

The efficient antimycotic agent aureobasidin A, isolated from the cult ure broth of Aureobasidium pullulans R 106, and the [(R)-Pro(9)]-aureo basidin A were prepared starting from benzyl N-Boc-N-methyl-(S)-beta-t riethylsiloxyvalinate, the synthesis of which is described here. The e asy accessibility of the tripeptolide benzyl l-beta-hydroxyvalyl-(2R)- oxy-(3R)-methylpentanoate [Boc-Leu-HOMeVal-(R)-HMP-OBn] facilities the construction of the cyclopeptolides 28, 34, 45 and 47. The peptide bo nds of the N-methylamino acids were formed with the help of 7-azabenzo triazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophophate. The rings of [(R)-Prog(9)]-aureobasidin A and of cyclopeptolides 28, 34, 45 and 47 were closed by way of pentafluorophenyl esters. The ring of aureob asidin A could only be formed with bromo-tris-pyrrolidinophosphonium h exafluorophosphate.