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

Publication Date:
31 December 2000 (online)

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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