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Solid‐Phase Total Synthesis of the Proposed Structure of Coibamide A and Its Derivative: Highly Methylated Cyclic Depsipeptides
Author(s) -
Sable Ganesh A.,
Park Jaekwan,
Kim Hyunsik,
Lim SooJeong,
Jang Soonmin,
Lim Dongyeol
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500697
Subject(s) - depsipeptide , chemistry , natural product , derivative (finance) , methylation , stereochemistry , total synthesis , solid phase synthesis , nuclear magnetic resonance spectroscopy , phase (matter) , mass spectrometry , combinatorial chemistry , organic chemistry , peptide , chromatography , biochemistry , financial economics , economics , gene
The solid‐phase total synthesis of the proposed structure of cyclic depsipeptide coibamide A and its derivative O ‐desmethyl coibamide A is reported. In this study, we demonstrate the solid‐phase synthetic strategy and final solution‐phase O ‐methylation for highly N ‐methylated cyclic depsipeptides. On‐resin macrocyclization, N , N ‐dimethylation and solution‐phase O ‐methylation were the key steps of these syntheses. The mass of synthetic coibamide A is consistent with that of the natural product according to liquid chromatography‐mass spectroscopy (LCMS) analysis but significant differences are observed upon 1 H and 13 C NMR analysis. The 2D NMR analysis and modeling studies of the synthetic compound compared with the isolated natural compound revealed that either they are conformationally different or the stereochemistry of the natural product was incorrectly assigned.