具有三氟甲基酮基团的谷氨酸和谷氨酰胺肽作为严重急性呼吸综合征冠状病毒3CL蛋白酶抑制剂的合成。

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

作者信息

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

机构信息

Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto 607-8412, Japan.

Department of Biology, Johns Hopkins University, Baltimore, MD, USA.

出版信息

Tetrahedron. 2006 Sep 4;62(36):8601-8609. doi: 10.1016/j.tet.2006.06.052. Epub 2006 Jul 14.

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