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【结 构 式】 
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【药物名称】RK-682 【化学名称】3-Hexadecanoyl-5-(hydroxymethyl)tetrahydrofuran-2,4-dione 【CA登记号】 【 分 子 式 】C21H36O5 【 分 子 量 】368.51807 |
【开发单位】 【药理作用】Pharmacological Tools, Heparanase Inhibitors, Protein Phosphatase Inhibitors |
合成路线1
An efficient synthesis of the optically active compound has been reported. Acid hydrolysis of the chiral acetonide (I) gave dihydroxy ester (II), which was selectively protected at the primary hydroxyl group as the O-trityl derivative (III). The beta-keto thioester (V) was obtained by condensation of palmitic acid (IV) with the magnesium salt of [(tert-butylthio)carbonyl]acetic acid via activation with carbonyl diimidazole. Silver salt-promoted condensation of thioester (V) with hydroxy ester (III) gave adduct (VI). The 3-acyltetronic acid system (VII) was obtained by cyclization of (VI) in the presence of tetrabutylammonium fluoride. Finally, deprotection of the trityl group using 1 N HCl afforded the title compound.
| 【1】 Sodeoka, M.; et al.; Asymmetric synthesis of a 3-acyltetronic acid derivative, RK-682, and formation of its calcium salt during silica gel column chromatography. Chem Pharm Bull 2001, 49, 2, 206. |
| 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) | 20917 | methyl (4R)-2,2-dimethyl-1,3-dioxolane-4-carboxylate | 52373-72-5 | C7H12O4 | 详情 | 详情 |
| (II) | 20916 | methyl (2R)-2,3-dihydroxypropanoate | C4H8O4 | 详情 | 详情 | |
| (III) | 46955 | methyl (2R)-2-hydroxy-3-(trityloxy)propanoate | C23H22O4 | 详情 | 详情 | |
| (IV) | 27918 | palmitic acid | 57-10-3 | C16H32O2 | 详情 | 详情 |
| (V) | 46956 | S-(tert-butyl) 3-oxooctadecanethioate | C22H42O2S | 详情 | 详情 | |
| (VI) | 46957 | (1R)-2-methoxy-2-oxo-1-[(trityloxy)methyl]ethyl 3-oxooctadecanoate | C41H54O6 | 详情 | 详情 | |
| (VII) | 46958 | (5R)-3-palmitoyl-5-[(trityloxy)methyl]-2,4(3H,5H)-furandione | C40H50O5 | 详情 | 详情 |