TOTAL SYNTHESIS OF 4-EPI-A83586C - EPIMERIZATION IN A MACROLACTAMISATION MEDIATED BY BOP AND DMAP

Protected linear hexapeptide 2 undergoes a remarkably facile C(4)-epim erisation when macrolactamisation is attempted with BOP [benzotriazol- 1-yloxy-tris(dimethylamino hexafluorophosphate] and DMAP in CH2Cl2 und er conditions of high-dilution; compound 6 is isolated in 51% yield fr om this reaction. In order to confirm its structure, 6 was independent ly synthesised from 18 by macrolactamisation with HATU 7-azabenzotriaz o1-1-yl)N,N,N:N'-tetramethyluronium hexafluorophosphate)] and NEM (N-e thylmorpholine); ring-closure now proceeded in 70% yield. After subseq uent deprotection by catalytic hydrogenolysis, amine salt 7 was chemos electively coupled to activated ester 5 to give 4-epi-A83586C (8) afte r glycal hydration.