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The ‘Azirine/Oxazolone Method’ in Peptaibol Synthesis: Preparation of a Derivative of Trichotoxin A‐50 (G)
Author(s) -
Altherr Werner,
Linden Anthony,
Heimgartner Heinz
Publication year - 2007
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200790102
Subject(s) - azirine , chemistry , oxazolone , synthon , amide , reagent , stereochemistry , protecting group , hydrolysis , peptide , derivative (finance) , yield (engineering) , cyclic peptide , amino acid , organic chemistry , biochemistry , ring (chemistry) , alkyl , materials science , financial economics , economics , metallurgy
The synthesis of a mixture of epimeric derivatives of the peptaibol trichotoxin A‐50 (G) is described. The ‘azirine/oxazolone method’ has been used as a superior method for the introduction of the Aib as well as the Iva units into the peptide chain. In this protocol, 2,2‐disubstituted 2 H ‐azirin‐3‐amines are the synthons for 2,2‐disubstituted glycines, which undergo coupling with N‐protected amino or peptide acids in high yield, and without any need of coupling reagents. The problem of the instability of the amide function of the Gln side chain under the conditions of the acid‐catalyzed hydrolysis of Z‐Gln‐(Aib) n ‐N(Me)Ph was solved by using an appropriate protecting group for the amide function of the Gln side chain, e.g. , the triphenylmethyl (trityl; Tr) group. The structures of two intermediate peptides, i.e. , the segments comprising residues 1–5 and 10–13, resp., were established by X‐ray crystallography.