Total Synthesis of 4-Epi-A83586C. Epimerisation in a Macrolactamisation Mediated by BOP and DMAP

Karl J. Hale; Jiaqiang Cai; Glyn Williams

doi:10.1055/s-1998-1606

Synlett 1998; 1998(2): 149-152
DOI: 10.1055/s-1998-1606

letter

© Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations published therein, is legally protected by copyright for the duration of the copyright period. Any use, exploitation or commercialization outside the narrow limits set by copyright legislation, without the publisher's consent, is illegal and liable to criminal prosecution. This applies in particular to photostat reproduction, copying, cyclostyling, mimeographing or duplication of any kind, translating, preparation of microfilms, and electronic data processing and storage.

Total Synthesis of 4-Epi-A83586C. Epimerisation in a Macrolactamisation Mediated by BOP and DMAP

Karl J. Hale^* , Jiaqiang Cai, Glyn Williams

^*The Christopher Ingold Laboratories, Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, UK; Fax +44-1 71-3 80-74 63; E-mail: k.j.hale@ucl.ac.uk

Abstract

als PDF herunterladen Alle Artikel dieser Rubrik

Protected linear hexapeptide 2 undergoes a remarkably facile C(4)-epimerisation when macrolactamisation is attempted with BOP [benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate] and DMAP in CH₂Cl₂ under conditions of high-dilution; compound 6 is isolated in 51% yield from this reaction. In order to confirm its structure, 6 was independently synthesised from 18 by macrolactamisation with HATU [O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate] and NEM (N-ethylmorpholine); ring-closure now proceeded in 70% yield. After subsequent deprotection by catalytic hydrogenolysis, amine salt 7 was chemoselectively coupled to activated ester 5 to give 4-epi-A83586C (8) after glycal hydration.

A83586C - antitumour antibiotic - macrolactamisation - peptide bond formation - amino-acid chlorides - peptide solution-conformation - cyclodepsipeptide

PDF (131 kb)