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【结 构 式】 
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【分子编号】35460 【品名】(3S)-3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid 【CA登记号】 |
【 分 子 式 】C14H20O4 【 分 子 量 】252.3104 【元素组成】C 66.65% H 7.99% O 25.36% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 5-(4-hydroxyphenyl)-2-methyl-3-pentanone (I) with benzyl acetate (II) by means of LDA in THF gives 3-hydroxy-5-(4-hydroxyphenyl)-3-isopropylpentanoic acid benzyl ester (III), which is treated with H2 over Pd/C in methanol to yield the corresponding free acid (IV) as a racemic mixture. Optical resolution of (IV) with (S)-alpha-methylbenzylamine ((S)-MBA) affords the (S)-isomer (V), which is cyclized with the magnesium salt of the monoethyl malonate by means of CDI in THF giving 4-hydroxy-6(S)-[2-(4-hydroxyphenyl)ethyl]-6-isopropyl-5,6-dihydro-2H-pyran-2-one (VI). Finally, this compound is condensed with toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester (VII) by means of K2CO3 in DMF.
| 【1】 Vara Prasad, J.V.N.; Domagala, J.M.; Boyer, F.E.; et al.; 5,6-Dihydropyran-2-ones possessing various sulfonyl functionalities: Potent nonpeptidic inhibitors of HIV protease. J Med Chem 2000, 43, 5, 843. |
| 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) | 35456 | 1-(4-hydroxyphenyl)-4-methyl-3-pentanone | C12H16O2 | 详情 | 详情 | |
| (II) | 35457 | benzyl acetate | 140-11-4 | C9H10O2 | 详情 | 详情 |
| (III) | 35458 | benzyl 3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoate | C21H26O4 | 详情 | 详情 | |
| (IV) | 35459 | 3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid | C14H20O4 | 详情 | 详情 | |
| (V) | 35460 | (3S)-3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid | C14H20O4 | 详情 | 详情 | |
| (VI) | 35461 | (6S)-4-hydroxy-6-(4-hydroxyphenethyl)-6-isopropyl-5,6-dihydro-2H-pyran-2-one | C16H20O4 | 详情 | 详情 | |
| (VII) | 35462 | S-[4-amino-2-(tert-butyl)-5-methylphenyl] 4-methylbenzenesulfonothioate | C18H23NO2S2 | 详情 | 详情 |