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【结 构 式】 
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【药物名称】 【化学名称】(±)-(3aS*,5R*,6aS*)-5-Amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid 【CA登记号】 【 分 子 式 】C8H10N2O5 【 分 子 量 】214.1793 |
【开发单位】Danish University of Pharmaceutical Sci. (Originator), Università degli Studi di Catanzaro (Originator), Università degli Studi di Messina (Originator), Università degli Studi di Milano (Originator) 【药理作用】Antiepileptic Drugs, NEUROLOGIC DRUGS, Metabotropic Glutamate Receptor Antagonists, NMDA Antagonists |
合成路线1
The mono-Boc protected amino cyclopentenecarboxylate (I) is converted to the di-Boc derivative (II) by means of di-tert-butyl dicarbonate and DMAP. Dipolar cycloaddition of the nitrile oxide generated from ethyl 2-chloro-2-(hydroxyimino)acetate (III) to cyclopentene (II) gives the cis-fused cyclopentaisoxazole (IV) as a diastereomeric mixture. After cleavage of the acidic Boc groups, the desired isomer (V) can be isolated by column chromatography. Finally, alkaline hydrolysis of the ethyl ester functions of (V) affords the target dicarboxylic acid.
| 【1】 Conti, P.; De Amici, M.; Di Ventimiglia, S.J.; Stensbol, T.B.; Madsen, U.; Brauner-Osborne, H.; Russo, E.; De Sarro, G.; Bruno, G.; De Micheli, C.; Synthesis and anticonvulsant activity of novel bicyclic acidic amino acids. J Med Chem 2003, 46, 14, 3102. |
| 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) | 64706 | ethyl 1-[(tert-butoxycarbonyl)amino]-3-cyclopentene-1-carboxylate | C13H21NO4 | 详情 | 详情 | |
| (II) | 64707 | ethyl 1-[bis(tert-butoxycarbonyl)amino]-3-cyclopentene-1-carboxylate | C18H29NO6 | 详情 | 详情 | |
| (III) | 30424 | 2-ethoxy-N-hydroxy-2-oxoethanimidoyl chloride | 14337-43-0 | C4H6ClNO3 | 详情 | 详情 |
| (IV) | 64708 | diethyl (3aS,6aS)-5-[bis(tert-butoxycarbonyl)amino]-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylate | C22H34N2O9 | 详情 | 详情 | |
| (V) | 64709 | diethyl (3aS,5R,6aS)-5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylate | C12H18N2O5 | 详情 | 详情 |