Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors

Magne O. Sydnes, Yoshio Hayashi, Vinay K. Sharma, Takashi Hamada, Usman Bacha, Jennifer Barrila, Ernesto Freire, Yoshiaki Kiso

Research output: Contribution to journalArticle

Abstract

Trifluoromethyl-β-amino alcohol 11 [(4S)-tert-butyl 4-amino-6,6,6-trifluoro-5-hydroxyhexanoate] was synthesized in five steps starting from Cbz-l-Glu-OH 5 where the key step involved the introduction of the trifluoromethyl (CF3) group to oxazolidinone 7, resulting in the formation of silyl ether 8 [(4S,5S)-benzyl 4-(2-(tert-butoxycarbonyl)ethyl)-5-(trifluoromethyl)-5-(trimethylsilyloxy)oxazolidine-3-carboxylate]. Compound 11 was then converted into four tri- and tetra-glutamic acid and glutamine peptides (1-4) possessing a CF3-ketone group that exhibited inhibitory activity against severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CLpro).

Original languageEnglish (US)
Pages (from-to)8601-8609
Number of pages9
JournalTetrahedron
Volume62
Issue number36
DOIs
StatePublished - Sep 4 2006

Keywords

  • Protease inhibitors
  • Severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CL)
  • Trifluoromethyl ketone

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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