Synlett 2017; 28(15): 1944-1949
DOI: 10.1055/s-0036-1589055
cluster
© Georg Thieme Verlag Stuttgart · New York

Cysteine-Free Intramolecular Ligation of N-Sulfanylethylanilide Peptide Using 4-Mercaptobenzylphosphonic Acid: Synthesis of Cyclic Peptide Trichamide

Keisuke Aiharaa, Tsubasa Inokumaa, Takahisa Jichua, Zhenjian Linb, Feixue Fuc, Kosuke Yamaokaa, Akira Shigenagaa, David A. Hutchinsc, Eric W. Schmidtb, Akira Otaka*a
  • aInstitute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
  • bDepartment of Medicinal Chemistry, University of Utah, Salt Lake City UT 84112, USA
  • cDepartment of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
This 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.
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Publication History

Received: 24 April 2017

Accepted after revision: 24 May 2017

Publication Date:
06 July 2017 (eFirst)

Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis

Abstract

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.

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