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

doi:10.1016/j.tet.2006.06.052

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 journal › Article › peer-review

45 Scopus citations

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 3CL^pro).

Original language	English (US)
Pages (from-to)	8601-8609
Number of pages	9
Journal	Tetrahedron
Volume	62
Issue number	36
DOIs	https://doi.org/10.1016/j.tet.2006.06.052
State	Published - Sep 4 2006
Externally published	Yes

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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10.1016/j.tet.2006.06.052

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@article{c780b85c421240b998afe2989cc01a29,

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

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).",

keywords = "Protease inhibitors, Severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CL), Trifluoromethyl ketone",

author = "Sydnes, {Magne O.} and Yoshio Hayashi and Sharma, {Vinay K.} and Takashi Hamada and Usman Bacha and Jennifer Barrila and Ernesto Freire and Yoshiaki Kiso",

note = "Funding Information: This research was supported by various grants from MEXT (Ministry of Education, Culture, Sports, Science, and Technology, Japan: the {\textquoteleft}Academic Frontier{\textquoteright} Project for Private Universities: matching fund subsidy from MEXT, the 21st Century Center of Excellence Program {\textquoteleft}Development of Drug Discovery Frontier Integrated from Tradition to Proteome{\textquoteright} and Grant-in-Aid for Scientific Research on Priority Areas 17035085) and the National Institutes of Health (GM 57144, USA). We thank Dr. J.-T. Nguyen for valuable help during manuscript preparation. ",

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language = "English (US)",

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T1 - Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors

AU - Sydnes, Magne O.

AU - Hayashi, Yoshio

AU - Sharma, Vinay K.

AU - Hamada, Takashi

AU - Bacha, Usman

AU - Barrila, Jennifer

AU - Freire, Ernesto

AU - Kiso, Yoshiaki

N1 - Funding Information: This research was supported by various grants from MEXT (Ministry of Education, Culture, Sports, Science, and Technology, Japan: the ‘Academic Frontier’ Project for Private Universities: matching fund subsidy from MEXT, the 21st Century Center of Excellence Program ‘Development of Drug Discovery Frontier Integrated from Tradition to Proteome’ and Grant-in-Aid for Scientific Research on Priority Areas 17035085) and the National Institutes of Health (GM 57144, USA). We thank Dr. J.-T. Nguyen for valuable help during manuscript preparation.

PY - 2006/9/4

Y1 - 2006/9/4

N2 - 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).

AB - 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).

KW - Protease inhibitors

KW - Severe acute respiratory syndrome coronavirus protease (SARS-CoV 3CL)

KW - Trifluoromethyl ketone

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

Abstract

Keywords

ASJC Scopus subject areas

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