Convenient route to Fmoc-homotyrosine via metallaphotoredox catalysis and its use in the total synthesis of anabaenopeptin cyclic peptides

• 全文链接
• 请求原文

作   者：

Biron, Eric;  Berube, Christopher;  Guay, Louis-David;  Fraser, Tommy;  Lapointe, Victor;  Cardinal, Sebastien; 

作者机构：

Univ Quebec Rimouski;  Univ Laval; 

关键词：

POTENT CARBOXYPEPTIDASE;  METABOLITES;  SPONGE;  CYANOBACTERIAL PEPTIDES;  ACIDS;  AERUGINOSA BLOOM MATERIAL;  WATER BLOOM;  OSCILLAMIDE-Y;  PROTEASE INHIBITORS;  TAFIA; 

期刊名称：

Organic & biomolecular chemistry

i s s n：

1477-0520

年卷期：

2023 年 21 卷 45 期

页   码：

9011-9020

页   码：

摘   要：

Herein, we report the first solid-phase total synthesis of the natural cyclic peptide anabaenopeptin F and the use of metallaphotoredox catalysis to overcome the key challenges associated with the preparation of the non-proteinogenic amino acid homotyrosine contained in these peptides. Starting from l-homoserine, enantiopure Fmoc-protected homotyrosine was prepared in a straightforward manner by metallaphotoredox catalysis with N-Fmoc-(S)-2-amino-4-bromobutanoic acid and 4-tert-butoxybromobenzene partners. The prepared protected amino acid was used in solid-phase peptide synthesis to achieve the total synthesis of anabaenopeptin F and establish the stereochemistry of the isoleucine residue. Protease inhibition studies with the synthesized anabaenopeptin F showed inhibitory activities against carboxypeptidase B in the low nanomolar range. The high convergency of the synthetic methodologies paves the way for the rapid access to N-Fmoc-protected non-proteinogenic and unnatural amino acids and the total synthesis of complex bioactive peptides containing these amino acids.