Affiliation:
1. Department of Basic Medicinal Sciences Graduate School of Pharmaceutical Sciences Nagoya University Furo-cho 464-8601 Nagoya Chikusa-ku Japan
2. School of Life Science and Technology Tokyo Institute of Technology 4259 Nagatsuta-cho 226-8503 Yokohama Midori-ku Japan
3. Laboratory for Chemistry and Life Science Institute of Innovative Research Tokyo Institute of Technology 4259 Nagatsuta-cho 226-8503 Yokohama Midori-ku Japan
Abstract
AbstractAlthough cyclic peptides have become increasingly important as drugs, the most conventional peptide cyclization method using moderately active coupling agents suffers from a lot of waste and high cost as well as long reaction times and burdensome purification. Herein, we report an unconventional approach to peptide cyclization that uses acylammonium species generated from inexpensive and less wasteful Me2NBn and ClCO2i‐Pr. Using this approach, we observed the desired rapid activation of the C‐terminus of cyclization precursors by an acylammonium ion for rapid and epimerization/dimerization‐free cyclization of synthetically challenging peptides, including a difficult cyclization involving N‐methyl amide bond formation. The ease of purification, productivities, and reaction mass efficiencies of our approach were significantly superior to those in previous reports. We synthesized a previously reported versicotide D analogue, and our data indicated that its assigned stereostructure should be revised.
Funder
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
Subject
General Chemistry,Catalysis
Cited by
2 articles.
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