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

27 Citations (Scopus)

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
Externally publishedYes

Fingerprint

SARS Virus
Amino Alcohols
Oxazolidinones
Severe Acute Respiratory Syndrome
Coronavirus
Protease Inhibitors
Ketones
Glutamine
Ether
Glutamic Acid
Peptide Hydrolases
Peptides
oxazolidine

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors. / Sydnes, Magne O.; Hayashi, Yoshio; Sharma, Vinay K.; Hamada, Takashi; Bacha, Usman; Barrila, Jennifer; Freire, Ernesto; Kiso, Yoshiaki.

In: Tetrahedron, Vol. 62, No. 36, 04.09.2006, p. 8601-8609.

Research output: Contribution to journalArticle

Sydnes, Magne O. ; Hayashi, Yoshio ; Sharma, Vinay K. ; Hamada, Takashi ; Bacha, Usman ; Barrila, Jennifer ; Freire, Ernesto ; Kiso, Yoshiaki. / Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors. In: Tetrahedron. 2006 ; Vol. 62, No. 36. pp. 8601-8609.
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AU - Hayashi, Yoshio

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AU - Hamada, Takashi

AU - Bacha, Usman

AU - Barrila, Jennifer

AU - Freire, Ernesto

AU - Kiso, Yoshiaki

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