Solid‐Phase Total Synthesis of the Proposed Structure of Coibamide A and Its Derivative: Highly Methylated Cyclic Depsipeptides. Issue 32 (1st October 2015)

• Record Type: Journal Article
• Authors: Sable, Ganesh A.; Park, Jaekwan; Kim, Hyunsik; Lim, Soo‐Jeong; Jang, Soonmin; Lim, Dongyeol
• Is Part Of: European journal of organic chemistry. Issue 32(2015)
• Page Start: 7043
• Page End: 7052
• Publication Date: 2015-10-01
• Subjects: Total synthesis -- Solid‐phase synthesis -- Natural products -- Peptides -- Configuration determination -- Medicinal chemistry; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201500697
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: 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. Abstract : Solid‐phase total synthesis of the proposed structure of coibamide A and O ‐desmethyl coibamide A has been accomplished. The synthetic samples were studied by 2D NMR spectroscopic analysis and by computational modeling.