Synthesis 2020; 52(23): 3657-3666
DOI: 10.1055/s-0040-1707238
paper
© Georg Thieme Verlag Stuttgart · New York

One-Pot Ring-Opening Peptide Synthesis Using α,α-Difluoro-β-Lactams

Atsushi Tarui
,
Masakazu Ueo
,
Marino Morikawa
,
Masahiko Tsuta
,
Sumika Iwasaki
,
Noriko Morishita
,
Yukiko Karuo
,
Kazuyuki Sato
,
Kentaro Kawai
,
Masaaki Omote
Faculty of Pharmaceutical Sciences, Setsunan University, Hirakata, Osaka 573-0101, Japan   eMail: omote@pharm.setsunan.ac.jp
› Institutsangaben

This work was supported by JSPS KAKENHI Grant Number JP16K18855.
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Publikationsverlauf

Received: 17. Juni 2020

Accepted after revision: 09. Juli 2020

Publikationsdatum:
17. August 2020 (online)


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Abstract

α,α-Difluoro-β-lactams successfully underwent ring-opening aminolysis with various amino acids in 2,2,2-trifluoroethanol to afford fluorine-containing peptides. In this aminolysis, it was found that 2,2,2-trifluoroethanol first attacked the α,α-difluoro-β-lactams with cleavage of lactam ring to form the corresponding open-chain 2,2,2-trifluoroethyl esters as reactive intermediates. The trifluoroethyl esters were more electrophilic compared with the corresponding methyl ester and thereby accelerated the aminolysis with various amino acids to form β-amino acid peptides with α,α-difluoromethylene unit.

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