Cysteine-Free Intramolecular Ligation of N-Sulfanylethylanilide Peptide Using 4-Mercaptobenzylphosphonic Acid: Synthesis of Cyclic Peptide TrichamideThis research was supported in part by a Grant-in-Aid for Scientiﬁc Research (KAKENHI). K.A. is grateful for a JSPS fellowship (14J07568). T.J. is grateful for SUNBOR SCHOLARSHIP.
Received: 24 April 2017
Accepted after revision: 24 May 2017
06 July 2017 (eFirst)
Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis
An N-sulfanylethylanilide (SEAlide)-based ligation was developed for the preparation of trichamide, a thiazole-containing cyclic peptide isolated from bloom-forming cyanobacterium Trichodesmium erythraeum. In this cysteine-free ligation, 4-mercaptobenzylphosphonic acid (MBPA) functions as a dual promoter both for the N–S acyl-transfer-mediated activation of the SEAlide unit and for subsequent ligation. Furthermore, we established a high-yielding route to enantiomerically pure thiazole amino acids using a one-pot Hantzsch process.