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【结 构 式】 
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【药物名称】2-Benzylthio-ATPalphaS 【化学名称】2-Benzylsulfanyl-5'-O-(1-thiotriphosphate)adenosine 【CA登记号】246150-03-8 (R-isomer), 246150-04-9 (S-isomer), 246150-02-7 (undefined isomer) 【 分 子 式 】C17H22N5O12P3S2 【 分 子 量 】645.44059 |
【开发单位】Bar-Ilan University (Originator), Université Montpellier I (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Insulin Secretagogues, P2Y Agonists |
合成路线1
Treatment of adenosine (I) with H2O2 and HOAc affords N-oxide (II), which is converted into the benzyloxime (IV) via N-benzyloxyadenosine perchlorate (III). Treatment of (IV) with CS2 and NaOH in MeOH followed by separation by filtration and chromatography yields 2-thioadenosine (V), which is then converted into the sodium thiolate salt by treatment with NaOH in MeOH and condensed with benzylbromide (VI) in DMF, providing derivative (VII). Finally, conversion of (VII) into the target compound is achieved by following these steps: (i) treatment of (VII) with thiophosphoryl chloride (PSCl3) in pyridine; (ii) addition of a mixture of Bu3N and (Bu3NH+)2P2O7H2 in DMF; and (iii) treatment with TEAB and chromatographic separation of regioisomers.
| 【1】 Kikugawa, K.; et al.; Platelet aggregation inhibitors. IX. Chemical transformation of adenosine into 2-thioadenosine derivatives. Chem Pharm Bull 1977, 25, 8, 1959. |
| 【2】 Fischer, B.; Chulkin, A.; Boyer, J.L.; Gendron, F.-P.; Chapal, J.; Petit, P.; Hillaire-Buys, D.; Harden, K.T.; Beaudoin, A.R.; 2-Thiother 5'-O-(1-thiotriphosphate)adenosine derivatives as new insulin secretagogues acting through P2Y-receptors. J Med Chem 1999, 42, 18, 3636. |
| 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) | 44895 | (2R,3R,4S)-2-(6-amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C10H13N5O4 | 详情 | 详情 | |
| (II) | 44891 | 6-amino-9-[(2R,3R,4S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-1-ium-1-olate | C10H13N5O5 | 详情 | 详情 | |
| (III) | 44892 | 6-amino-1-(benzyloxy)-9-[(2R,3R,4S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-9H-purin-1-ium perchlorate | C17H20ClN5O9 | 详情 | 详情 | |
| (IV) | 44893 | 5-amino-N'-(benzyloxy)-1-[(2R,3R,4S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1H-imidazole-4-carboximidamide | C16H21N5O5 | 详情 | 详情 | |
| (V) | 44896 | (2R,3R,4S)-2-(6-amino-2-sulfanyl-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C10H13N5O4S | 详情 | 详情 | |
| (VI) | 12912 | 1-(Bromomethyl)benzene; Alpha-bromotoluene | 100-39-0 | C7H7Br | 详情 | 详情 |
| (VII) | 44894 | (2R,3R,4S)-2-[6-amino-2-(benzylsulfanyl)-9H-purin-9-yl]-5-(hydroxymethyl)tetrahydro-3,4-furandiol | C17H19N5O4S | 详情 | 详情 |