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Synthesis of a Derivative of the Peptaibol‐Antibiotic Trichovirin I 1B by Means of the ‘Azirine/Oxazolone Method’
Author(s) -
Luykx Roeland T. N.,
Linden Anthony,
Heimgartner Heinz
Publication year - 2003
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200390339
Subject(s) - azirine , oxazolone , chemistry , synthon , stereochemistry , peptide , organic chemistry , biochemistry , ring (chemistry)
According to the earlier published synthesis of the C‐terminal nonapeptide of Trichovirin I 1B, Z‐Ser( t Bu)‐Val‐Aib‐Pro‐Aib‐Leu‐Aib‐Pro‐Leuol ( 5 ), the complete tetradecapeptide Z‐Aib‐Asn(Trt)‐Leu‐Aib‐Pro‐Ser( t Bu)‐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‐2 H ‐azirine‐3‐( N ‐methyl‐ N ‐phenylamine) ( 1a ) and methyl N ‐(2,2‐dimethyl‐2 H ‐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( t Bu)‐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.