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【结 构 式】 
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【分子编号】27983 【品名】1-phosphono-4-sulfanylbutylphosphonic acid 【CA登记号】 |
【 分 子 式 】C4H12O6P2S 【 分 子 量 】250.149204 【元素组成】C 19.21% H 4.84% O 38.38% P 24.76% S 12.82% |
合成路线1
该中间体在本合成路线中的序号：(IV)Tetraisopropyl methylenediphosphonate (I) was alkylated with 3-(acetylthio)propyl iodide (II) in the presence of NaH to give (III). Then, hydrolysis of both thioester and phosphonate esters of (III) with refluxing HCl provided the intermediate thiol (IV).
| 【1】 Gil, L.; et al.; Prostaglandin E2-bisphosphonate conjugates: Potential agents for treatment of osteoporosis. Bioorg Med Chem 1999, 7, 5, 901. |
| 【2】 Gil, L.; Young, R.N.; Ruel, R.; Han, Y. (Merck Frosst Canada Inc.); Prostaglandin conjugates for treating or preventing bone disease. US 6121253; WO 0031084 . |
| 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) | 27980 | Diisopropyl (diisopropoxyphosphoryl)methylphosphonate; Tetraisopropyl methylenediphosphonate | 1660-95-3 | C13H30O6P2 | 详情 | 详情 |
| (II) | 27981 | S-(3-iodopropyl) ethanethioate | C5H9IOS | 详情 | 详情 | |
| (III) | 27982 | S-[4,4-bis(diisopropoxyphosphoryl)butyl] ethanethioate | C18H38O7P2S | 详情 | 详情 | |
| (IV) | 27983 | 1-phosphono-4-sulfanylbutylphosphonic acid | C4H12O6P2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Selective acylation of the silyl ester of prostaglandin E2 (V) at C-15 hydroxyl group with bromoacetyl bromide in the presence of pyridine at -25 C afforded bromoacetate ester (VI). Then, displacement of the halogen atom with thiol (IV) in aqueous dioxan furnished the correspondig desilylated sulfide. This was finally converted into the title disodium phosphonate salt by treatment with cation exchange resin.
| 【1】 Gil, L.; et al.; Prostaglandin E2-bisphosphonate conjugates: Potential agents for treatment of osteoporosis. Bioorg Med Chem 1999, 7, 5, 901. |
| 【2】 Gil, L.; Young, R.N.; Ruel, R.; Han, Y. (Merck Frosst Canada Inc.); Prostaglandin conjugates for treating or preventing bone disease. US 6121253; WO 0031084 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 14005 | 2-Bromoacetyl bromide; Bromoacetyl bromide | 598-21-0 | C2H2Br2O | 详情 | 详情 | |
| (IV) | 27983 | 1-phosphono-4-sulfanylbutylphosphonic acid | C4H12O6P2S | 详情 | 详情 | |
| (V) | 27984 | tert-butyl(diphenyl)silyl (Z)-7-[(1R,2R,3R)-3-hydroxy-2-[(E,3S)-3-hydroxy-1-octenyl]-5-oxocyclopentyl]-5-heptenoate | C36H50O5Si | 详情 | 详情 | |
| (VI) | 27985 | tert-butyl(diphenyl)silyl (Z)-7-((1R,2R,3R)-2-[(E,3S)-3-[(2-bromoacetyl)oxy]-1-octenyl]-3-hydroxy-5-oxocyclopentyl)-5-heptenoate | C38H51BrO6Si | 详情 | 详情 |