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 Aihara
a   Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
,
Tsubasa Inokuma
a   Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
,
Takahisa Jichu
a   Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
,
Zhenjian Lin
b   Department of Medicinal Chemistry, University of Utah, Salt Lake City UT 84112, USA
,
Feixue Fu
c   Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
,
Kosuke Yamaoka
a   Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
,
Akira Shigenaga
a   Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
,
David A. Hutchins
c   Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA
,
Eric W. Schmidt
b   Department of Medicinal Chemistry, University of Utah, Salt Lake City UT 84112, USA
,
Akira Otaka*
a   Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan   Email: aotaka@tokushima-u.ac.jp
› Author Affiliations
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.
Further Information

Publication History

Received: 24 April 2017

Accepted after revision: 24 May 2017

Publication Date:
06 July 2017 (online)


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.

Supporting Information