Attempts toward the Synthesis of the Peptaibol Antiamoebin by Using the ‘Azirine/Oxazolone Method’

The two segments, 1–9 and 10–16, of the peptaibol antibiotic antiamoebin I, i.e. , the nonapeptide Ac‐Phe‐Aib‐Aib‐Aib‐ D , L ‐Iva‐Gly‐Leu‐Aib‐Aib‐OH ( 15 ) and the heptapeptide Z‐Hyp‐Gln‐ D , L ‐Iva‐Hyp‐Aib‐Pro‐Pheol ( 34 ), have been prepared as mixtures of the epimers containing D , L ‐Iva. All α , α ‐disubstituted α ‐amino acids were introduced by the ‘azirine/oxazolone method’, in which amino or peptide acids are coupled with the corresponding 2 H ‐azirin‐3‐amines, followed by selective hydrolysis of the terminal amide bond. The amino acids Hyp and Gln were introduced as Z‐protected 4 ) (2 S ,4 R )‐4‐( tert ‐butoxy)proline ( 19 ) and methyl N ‐[bis(4‐methoxyphenyl)methyl]glutamine ( 26 ). Coupling of peptide segments was achieved via the ‘mixed anhydride’ method, the DCC/HOBt or TBTU/HOBt strategy. The crystal structure of the segment 6–9 was determined by X‐ray crystallography and displayed the presence of a β ‐turn conformation.