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【结 构 式】 
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【药物名称】LY-389795 【化学名称】(1R,4R,5S,6R)-4-Amino-2-thiabicyclo[3.1.0]hexane-4,6-dicarboxylic acid 【CA登记号】191471-53-1 (stereoisomer) 【 分 子 式 】C7H9NO4S 【 分 子 量 】203.21808 |
【开发单位】Lilly (Originator) 【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, mglu2 Agonists, mglu3 Agonists |
合成路线1
Cycloaddition of ethyl diazoacetate to thiophene (I) in the presence of dirhodium tetraacetate gave bicyclic compound (II). Hydroboration of the olefin double bond of (II), followed by oxidative treatment with hydrogen peroxide provided alcohol (III), which was oxidized to ketone (IV) under Swern conditions. The Bucherer-Bergs reaction of (IV) with potassium cyanide and ammonium carbonate produced the spiro hydantoin (V). Hydrolysis of the hydantoin ring in boiling aqueous NaOH then yielded the title compound.
| 【1】 Massey, S.M.; Monn, J.A.; Valli, M.J. (Eli Lilly and Company); Excitatory amino acid derivs.. EP 0774461; JP 2000500748; WO 9718199 . |
| 【2】 Massey, S.M.; Monn, J.A.; Valli, M.J. (Eli Lilly and Company); Excitatory amino acid derivs.. US 5688826 . |
| 【3】 Levine, L.R. (Eli Lilly and Company); Treatment for premenstrual dysphoric disorder. WO 9832436 . |
| 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) | 13297 | Thiophene | 110-02-1 | C4H4S | 详情 | 详情 |
| (II) | 30084 | ethyl 2-thiabicyclo[3.1.0]hex-3-ene-6-carboxylate | C8H10O2S | 详情 | 详情 | |
| (III) | 30085 | ethyl (1R,4R,5S,6S)-4-hydroxy-2-thiabicyclo[3.1.0]hexane-6-carboxylate | C8H12O3S | 详情 | 详情 | |
| (IV) | 30086 | ethyl (1R,5S,6S)-4-oxo-2-thiabicyclo[3.1.0]hexane-6-carboxylate | C8H10O3S | 详情 | 详情 | |
| (V) | 30087 | (1'R,4S,5'S,6'S)-2,5-Dioxospiro[imidazolidine-4,4'-[2]thiabicyclo[3,1,0]hexane]-6'-carboxylic acid ethyl ester | C10H12N2O4S | 详情 | 详情 |