【结 构 式】 |
【药物名称】 【化学名称】4(R)-(1-Benzothien-2-ylmethyl)-D-glutamic acid 【CA登记号】400625-61-8 【 分 子 式 】C14H15NO4S 【 分 子 量 】293.34395 |
【开发单位】Lilly (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, Glutamate Racemase Inhibitors |
合成路线1
D-Glutamic acid (I) is treated with SOCl2 in EtOH to produce ethyl D-pyroglutamate (II). Further protection of (II) with di-tert-butyl dicarbonate yields the N-Boc pyroglutamate (III) (1). The lithiated derivative of (III) is alkylated with 2-(bromomethyl)benzothiophene (IV) to afford the trans alkylated isomer (V). Basic hydrolysis of (V) produces the N-Boc amino diacid (VI). Then, acidic Boc group cleavage in (VI), followed by treatment of the resultant hydrochloride salt with propylene oxide in MeOH leads to the free aminoacid (1,2).
【1】 De Dios, A.; Prieto, L.; Martin, J.A.; Rubio, A.; Ezquerra, J.; Tebbe, M.; López de Uralde, B.; Martín, J.; Sánchez, A.; LeTourneu, D.L.; McGee, J.E.; Boylan, C.; Parr, T.R.; Smith, M.C.; 4-Substituted D-glutamic acid analogues: The first potent inhibitors of glutamate racemase (MurI) enzyme with antibacterial activity. J Med Chem 2002, 45, 20, 4559. |
【2】 Martin, J.A.; Ezquerra-Carrera, J.; Tebbe, M.J.; De Dios, A.; Prieto, L.; McGee, J.E.; Rubio-Esteban, A.; Smith, M.C. (Eli Lilly and Company); Chemical cpds.. WO 0214261 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 54708 | (R)-(-)-Glutamic acid; (R)-2-Aminoglutaric acid; D-(+)-Glutamic acid; D-2-Aminoglutaric acid; D-glutamic acid | 6893-26-1 | C5H9NO4 | 详情 | 详情 |
(II) | 64464 | ethyl (2R)-5-oxo-2-pyrrolidinecarboxylate | C7H11NO3 | 详情 | 详情 | |
(III) | 43914 | 1-(tert-butyl) 2-ethyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate | 144978-35-8 | C12H19NO5 | 详情 | 详情 |
(IV) | 64465 | 2-(bromomethyl)-1-benzothiophene | C9H7BrS | 详情 | 详情 | |
(V) | 64466 | 1-(tert-butyl) 2-ethyl (2R,4R)-4-(1-benzothiophen-2-ylmethyl)-5-oxo-1,2-pyrrolidinedicarboxylate | C21H25NO5S | 详情 | 详情 | |
(VI) | 64467 | (2R,4R)-2-(1-benzothiophen-2-ylmethyl)-4-[(tert-butoxycarbonyl)amino]pentanedioic acid | C19H23NO6S | 详情 | 详情 |