Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors
Synthesis of glutamic acid and glutamine peptides possessing a trifluoromethyl ketone group as SARS-CoV 3CL protease inhibitors
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DOI：
10.1016/j.tet.2006.06.052
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发表时间：
2006-09-04
期刊：
影响因子：
2.1
通讯作者：
Kiso, Yoshiaki
中科院分区：
文献类型：
--
作者：
Sydnes, Magne O.;Hayashi, Yoshio;Kiso, Yoshiaki
三氟甲基-β-氨基醇11 [（4S）-叔丁基4-氨基-6，6，6-三氟-5-羟基己酸酯]由Cbz-L-Glu-OH 5开始经五步合成，其中关键步骤涉及将三氟甲基（CF 3）基团引入恶唑烷酮7，从而形成甲硅烷基醚8 [（4S，5S）-4-（2-（叔丁氧羰基）乙基）-5-（三氟甲基）-5-（三甲基甲硅烷基氧基）恶唑烷-3-甲酸苄酯]。然后将化合物11转化为具有CF 3-酮基团的四种三-和四-谷氨酸和谷氨酰胺肽（1-4），其表现出对严重急性呼吸综合征冠状病毒蛋白酶（SARS-CoV 3CL（pro））的抑制活性。(c)2006爱思唯尔有限公司保留所有权利。
Trifluoromethyl-beta-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)). (c) 2006 Elsevier Ltd. All rights reserved.