【结 构 式】 |
【药物名称】Forphenicinol, Forfenimex 【化学名称】L-2-(3-Hydroxy-4-hydroxymethylphenyl)glycine 【CA登记号】71522-58-2, 72973-11-6 ((+)-enantiomer) 【 分 子 式 】C9H11NO4 【 分 子 量 】197.19232 |
【开发单位】Banyu (Originator), Nippon Kayaku (Originator) 【药理作用】IMMUNOMODULATING AGENTS, Immunostimulants |
合成路线1
The partial reduction of dimethyl hydroxyterephthalate (I) with NaBH4 in refluxing methanol gives methyl-3-hydroxy-4-(hydroxymethyl)benzoate (II), which by reaction with 2,2-dimethoxypropane (III) by means of p-toluenesulfonic acid in benzene is converted into the benzo-1,3-dioxane (IV). The reduction of (IV) with sodium dihydro-bis(2-methoxyethoxy)aluminate (V) affords the protected benzyl alcohol (VI), which is oxidized with CrO3 to the benzaldehyde (VII). The reaction of (VII) with NaCN and ammonia in methanol yields the aminonitrile (VIII), which is finally hydrolyzed with Ba(OH)2 and afterwards with H2SO4.
【1】 Yoshizawa, J.; Ushijima, R.; Umezawa, H.; Takeuchi, T.; Morishima, H.; Synthesis of forphenicinol and forphenicine. J Antibiot 1982, 35, 11, 1500-06. |
【2】 Aoyagi, T.; Ishizuka, M.; Matsumoto, I,. Morishima, H.; Takeuchi, T.; Umezawa, H.; Yamamoto, T. (Microbial Chemistry Research Foundation); Pharmacological cpd. with immunopotentiating activity and production and uses thereof. US 4238507 . |
【3】 Arrigoni-Martelli, E.; Castaner, J.; Serradell, M.N.; Blancafort, P.; Forphenicinol. Drugs Fut 1983, 8, 7, 587. |
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) | 36152 | methyl 4-(acetoxy)-3-hydroxybenzoate | C10H10O5 | 详情 | 详情 | |
(II) | 36153 | methyl 3-hydroxy-4-(hydroxymethyl)benzoate | C9H10O4 | 详情 | 详情 | |
(III) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
(IV) | 36154 | methyl 2,2-dimethyl-4H-1,3-benzodioxine-7-carboxylate | C12H14O4 | 详情 | 详情 | |
(VI) | 36155 | (2,2-dimethyl-4H-1,3-benzodioxin-7-yl)methanol | C11H14O3 | 详情 | 详情 | |
(VII) | 36156 | 2,2-dimethyl-4H-1,3-benzodioxine-7-carbaldehyde | C11H12O3 | 详情 | 详情 | |
(VIII) | 36157 | 2-amino-2-(2,2-dimethyl-4H-1,3-benzodioxin-7-yl)acetonitrile | C12H14N2O2 | 详情 | 详情 |