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【结 构 式】 
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【分子编号】12798 【品名】9-[(2R,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-9H-purin-6-ol 【CA登记号】 |
【 分 子 式 】C16H24N4O3Si 【 分 子 量 】348.47722 【元素组成】C 55.15% H 6.94% N 16.08% O 13.77% Si 8.06% |
合成路线1
该中间体在本合成路线中的序号：(IV)3) The reaction of inosine (I) with tert-butyldimethylsilyl chloride by means of imidazole in DMF gives the 5'-O-silyl derivative (II), which by reaction with CS2 and 3-bromopropionitrile by means of NaOH in DMSO is converted into 5'-O-(tert-butyldimethylsilyl)-2',3'-bis-O-(2-cyanoethyldithiocarbonyl)inosine (III). The reaction of (III) with tri-n-butyltin hydride and AIBN in refluxing toluene affords 5'-O-(tert-butyldimethylsilyl-2',3'-dideoxy-2',3'-didehydroinosine (IV), which is deprotected with tetrabutylammonium fluoride in THF to 2',3'-dideoxy-2',3'-didehydroinosine (V). Finally, this compound is hydrogenated with H2 over Pd/C in ethanol - water. 4) The reaction of (II) with 1,1'-thiocarbonyldiimidazole (DTI) in DMF gives 5'-O-(tert-butyldimethylsilyl)-2',3'-O-(thionocarbonyl)inosine (VI), which by reaction with refluxing triethyl phosphite is converted into the didehydro derivative (IV), already obtained (5).
| 【1】 Webb, R.R. II, Wos, J.A.; Martin, J.C.; Brodfuehrer, P.R.; Synthesis of 2',3'-dideoxyinosine. Nucleosides Nucleotides 1988, 7, 2, 147-53. |
| 【2】 Chu, C.K.; Bhadti, V.S.; Doboszewski, B.; Gu, Z.P.; Kosugi, Y.; Pullaiah, K.C.; Van Roey, P.; General syntheses of 2',3'-dideoxynucleosides and 2',3'-didehydro-2',3'-dideoxynucleosides. J Org Chem 1989, 54, 2217-25. |
| 【3】 Prous, J.; Castaner, J.; DIDEOXYINOSINE. Drugs Fut 1990, 15, 6, 569. |
| 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) | 12795 | (2R,3S,4R,5R)-2-(Hydroxymethyl)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-3,4-furandiol; Inosine | 58-63-9 | C10H12N4O5 | 详情 | 详情 |
| (II) | 12796 | (2R,3S,4R,5R)-2-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-3,4-furandiol | C16H26N4O5Si | 详情 | 详情 | |
| (III) | 12797 | O-[(2R,3R,4R,5R)-2-([[tert-butyl(dimethyl)silyl]oxy]methyl)-4-([[(2-cyanoethyl)sulfanyl]carbothioyl]oxy)-5-(6-hydroxy-9H-purin-9-yl)tetrahydro-3-furanyl] S-(2-cyanoethyl) carbonodithioate | C24H32N6O5S4Si | 详情 | 详情 | |
| (IV) | 12798 | 9-[(2R,5S)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-9H-purin-6-ol | C16H24N4O3Si | 详情 | 详情 | |
| (V) | 12799 | 9-[(2R,5S)-5-(Hydroxymethyl)-2,5-dihydro-2-furanyl]-9H-purin-6-ol | C10H10N4O3 | 详情 | 详情 | |
| (VI) | 12800 | (3aR,4R,6R,6aR)-4-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-6-(6-hydroxy-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-2-thione | C17H24N4O5SSi | 详情 | 详情 |