Total synthesis of proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide

Total synthesis of the originally proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide, has been accomplished by using a [(4+1)+3+3]-peptide fragment-coupling strategy and careful examination and optimization of the multiple dense N-methylated amide-bond formations. The synthetic sample of the proposed coibamide A could not match the natural product in both H-1 and C-13 NMR spectra, but was found to exhibit low micromolar cytotoxicity against the proliferation of three tested cancer cells. (C) 2014 Elsevier Ltd. All rights reserved.