Synthesis of Complex Thiazoline‐Containing Peptides by Cyclodesulfhydration ofN‐Thioacyl‐2‐Mercaptoethylamine Derivatives

Abstract

Herein we report a mild, efficient, and epimerization‐free method for the synthesis of peptide‐derived 2‐thiazolines and 5,6‐dihydro‐4H‐1,3‐thiazines based on a cyclodesulfhydration of N‐thioacyl‐2‐mercaptoethylamine or N‐thioacyl‐3‐mercaptopropylamine derivatives. The described reaction can be easily carried out in aqueous solutions at room temperature and it is triggered by change of the pH, leading to complex thiazoline or dihydrothiazine derivatives without epimerization in excellent to quantitative yields. The new method was applied in the total synthesis of the marine metabolite mollamide F, resulting in the revision of its stereochemistry.

Synthesis and Structural Revision of the Cyclic Hexapeptide Dimers Antatollamides A and B

“…Additionally, mollamide F ( 5 ) isolated from Didemnum molle was reported by the Van Wagoner group . Though mollamide F ( 5 ) is a thioxazoline , -containing cyclic peptide derived from the sequence of cyclo (Pro-Pro- d Phe- d Cys-Ile-Val) ( 4 ), the sequence was recently revised as cyclo (Pro-Pro-Phe- d Cys-Ile-Val) ( 3 ) by Meleshin et al The conformation of the two Pro residues of 5 was determined as s - cis -Pro-1 and s - trans -Pro-2. 1 and 2 establish disulfide bonds to form homocoupling structures, and 5 is a thioxazoline-containing peptide because of the difference in the stereochemistries of the Phe residue between 1 , 2 , and 5 .…”