Download PDF
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
Further Information

Publication History

Publication Date:
31 December 2000 (online)

  PDF Download  Permissions and Reprints All articles of this category

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

      >