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Attempts toward the synthesis of the Peptaibol Antiamoebin I by using the 'Azirine/Oxazolone Method'


Blaser, Pia; Altherr, Werner; Linden, Anthony; Heimgartner, Heinz (2013). Attempts toward the synthesis of the Peptaibol Antiamoebin I by using the 'Azirine/Oxazolone Method'. Chemistry & Biodiversity, 10(5):920-941.

Abstract

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 alpha,alpha- disubstituted alpha-amino acids were introduced by the 'azirine/oxazolone method', in which amino or peptide acids are coupled with the corresponding 2H-azirin-3-amines, followed by selective hydrolysis of the terminal amide bond. The amino acids Hyp and Gln were introduced as Z-protected (2S,4R)-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 beta-turn conformation.

Abstract

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 alpha,alpha- disubstituted alpha-amino acids were introduced by the 'azirine/oxazolone method', in which amino or peptide acids are coupled with the corresponding 2H-azirin-3-amines, followed by selective hydrolysis of the terminal amide bond. The amino acids Hyp and Gln were introduced as Z-protected (2S,4R)-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 beta-turn conformation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:May 2013
Deposited On:21 May 2013 11:30
Last Modified:21 Nov 2017 16:43
Publisher:Wiley-VCH Verlag Berlin
ISSN:1612-1872
Funders:Swiss National Science Foundation, Stipendienfonds der Basler Chemischen Industrie, F. Hoffmann-La Roche AG, Basel
Publisher DOI:https://doi.org/10.1002/cbdv.201200386

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