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【结 构 式】 
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【分子编号】17629 【品名】[(2R,3S,4S,5R)-4-(acetoxy)-5-(6-amino-9H-purin-9-yl)-3-bromotetrahydro-2-furanyl]methyl acetate 【CA登记号】 |
【 分 子 式 】C14H16BrN5O5 【 分 子 量 】414.21574 【元素组成】C 40.6% H 3.89% Br 19.29% N 16.91% O 19.31% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The regioseletive deacetylation of 9-(2,5-diacetoxy-3-bromo-3-deoxy-beta-D-xylofuranosyl)adenine (XVIII) by means of beta-cyclodextrin/NaHCO3 in water or hydrazine monohydrate in ethanol gives 9-(5-acetoxy-3-bromo-3-deoxy-beta-D-xylofuranosyl)adenine (XIX), which is debrominated by hydrogenation over Pd/C in acetonitrile/water, affording 9-(5-acetoxy-3-deoxy-beta-D-xylofuranosyl)adenine (XX). Finally, this compound is fluorinated by means of diethylamido sulfur trifluoride in refluxing dichloromethane, yielding (XXI) and deacetylated with NH3 to the target compound.
| 【1】 Tanaka, Y.; Uchida, Y.; Shiragami, H.; Yukawa, T.; Iwagami, H.; Izawa, K.; A novel method for the synthesis of ddA and F-ddA via regioselective 2'-O-deacetylation of 9-(2, 5-di-O-acetyl-3-bromo-3-deoxy-beta-D-xylofuranosyl)adenine. Nucleosides Nucleotides 1992, 1, 391-400. |
| 【2】 Castaner, J.; Graul, A.; Silvestre, J.S.; Lodenosine. Drugs Fut 1998, 23, 11, 1176-1189. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 17629 | [(2R,3S,4S,5R)-4-(acetoxy)-5-(6-amino-9H-purin-9-yl)-3-bromotetrahydro-2-furanyl]methyl acetate | C14H16BrN5O5 | 详情 | 详情 | |
| (XIX) | 17630 | [(2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-3-bromo-4-hydroxytetrahydro-2-furanyl]methyl acetate | C12H14BrN5O4 | 详情 | 详情 | |
| (XX) | 17631 | [(2S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydro-2-furanyl]methyl acetate | C12H15N5O4 | 详情 | 详情 | |
| (XXI) | 17632 | [(2S,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl acetate | C12H14FN5O3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The reaction of adenosine (I) with triethyl orthoacetate (II) by means of Ts-OH in acetonitrile gives the bicyclic dioxolane (III), which is treated with acetyl bromide in dichloroethane to yield the acetylated bromonucleoside (IV). The debromination of (IV) by means of Bu3SnH in toluene affords the acetylated target compound (V), which is finally deprotected with ammonia in methanol.
| 【1】 Norman, D.G.; Reese, C.B.; A convenient preparation of 3'-deoxyadenosine. Synthesis 1983, 304. |
| 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) | 11988 | Adenosine; (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 58-61-7 | C10H13N5O4 | 详情 | 详情 |
| (II) | 12940 | 1,1-Diethoxyethyl ethyl ether; 1,1,1-Triethoxyethane; Triethyl orthoacetate | 78-39-7 | C8H18O3 | 详情 | 详情 |
| (III) | 49214 | [(3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2-ethoxy-2-methyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol | C14H19N5O5 | 详情 | 详情 | |
| (IV) | 17629 | [(2R,3S,4S,5R)-4-(acetoxy)-5-(6-amino-9H-purin-9-yl)-3-bromotetrahydro-2-furanyl]methyl acetate | C14H16BrN5O5 | 详情 | 详情 | |
| (V) | 49215 | [(2S,4R,5R)-4-(acetoxy)-5-(6-amino-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H17N5O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(IV)The reaction of adenosine (I) with 2-acetoxyisobutyryl bromide (A) gives the 3'-bromonucleoside (II) along with some 3'-bromo regioisomer (III). The reaction of the desired isomer (II) with HCl in methanol yields the intermediate acetylated 3'-bromonucleoside (V) and finally the 3'-bromo-3'-deoxyadenosine (VI). This compound is then debrominated by hydrogenation with H2 over Pd/C in ethanol/water.
| 【1】 Aman, S.; et al.; From adenosine to 3'-deoxyadenosine: Development and scale up. Org Process Res Dev 2000, 4, 6, 601. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 49211 | 1-(bromocarbonyl)-2-methylpropyl acetate | C7H11BrO3 | 详情 | 详情 | |
| (I) | 11988 | Adenosine; (2R,3R,4S,5R)-2-(6-Amino-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 58-61-7 | C10H13N5O4 | 详情 | 详情 |
| (II) | 49212 | (2R,3S,4S,5R)-2-(6-amino-9H-purin-9-yl)-4-bromo-5-[[(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)oxy]methyl]tetrahydro-3-furanyl acetate | C18H22BrN5O7 | 详情 | 详情 | |
| (III) | 36390 | (2R,3R,4S,5R)-5-(6-amino-9H-purin-9-yl)-4-bromo-2-[[(2,4,4-trimethyl-5-oxo-1,3-dioxolan-2-yl)oxy]methyl]tetrahydro-3-furanyl acetate | C18H22BrN5O7 | 详情 | 详情 | |
| (IV) | 17629 | [(2R,3S,4S,5R)-4-(acetoxy)-5-(6-amino-9H-purin-9-yl)-3-bromotetrahydro-2-furanyl]methyl acetate | C14H16BrN5O5 | 详情 | 详情 | |
| (V) | 49216 | (2R,3S,4R,5R)-2-(6-amino-9H-purin-9-yl)-4-bromo-5-(hydroxymethyl)tetrahydro-3-furanol | C10H12BrN5O3 | 详情 | 详情 |