Synthesis of a Derivative of the Peptaibol‐Antibiotic Trichovirin I 1B by Means of the ‘Azirine/Oxazolone Method’

According to the earlier published synthesis of the C‐terminal nonapeptide of Trichovirin I 1B, Z‐Ser(tBu)‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (5), the complete tetradecapeptide Z‐Aib‐Asn(Trt)‐Leu‐Aib‐Pro‐Ser(tBu)‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (11b), a protected Trichovirin I 1B, has now been prepared by means of the ‘azirine/oxazolone method’. With the exception of the N‐terminal Aib(1), all Aib residues were introduced by the coupling of the corresponding amino or peptide acids with 2,2‐dimethyl‐2H‐azirine‐3‐(N‐methyl‐N‐phenylamine) (1a) and methyl N‐(2,2‐dimethyl‐2H‐azirin‐3‐yl)‐L‐prolinate (3a) as the Aib and Aib‐Pro synthons, respectively. Single crystals of two segments, i.e., the N‐terminal hexapeptide Z‐Aib‐Asn(Trt)‐Leu‐Aib‐Pro‐Ser(tBu)‐OMe (23) and the C‐terminal octapeptide Z‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (17), were obtained and their structures have been established by X‐ray crystallography. Following the same strategy, the C‐terminal nonapeptide of Trichovirin I 4A, Z‐Ala‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol (26), was also synthesized and characterized by X‐ray crystallography.