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【结 构 式】 
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【分子编号】36390 【品名】(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 【CA登记号】 |
【 分 子 式 】C18H22BrN5O7 【 分 子 量 】500.30618 【元素组成】C 43.21% H 4.43% Br 15.97% N 14% O 22.39% |
合成路线1
该中间体在本合成路线中的序号：(XV)The reaction of adenosine (XIII) with 2-acetoxyisobutyryl bromide (XIV) in acetonitrile gives 3'-deoxy-3'-bromo-2'-O-acetyl-5'-(2,5,5-trimethyl-1,3-dioxolan-4-on-2-yl)adenosine (XV), which is submitted to hydrogenolysis with H2 over Pd/C in methanol containing triethylamine.
| 【1】 Russell, A.F.; et al.; Reaction of 2-acyloxyisobutyryl halides with nucleosides. II. Reactions of adenosine. J Am Chem Soc 1973, 95, 12, 4025-30. |
| 【2】 Castaner, J.; Hopkins, S.J.; Serradell, M.N.; Blancafort, P.; 2',3'-Dideoxyadenosine. Drugs Fut 1982, 7, 4, 244. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 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 |
| (XIV) | 12806 | 2-bromo-1,1-dimethyl-2-oxoethyl acetate; alpha-Acetoxy-isobutyryl bromide | 40635-67-4 | C6H9BrO3 | 详情 | 详情 |
| (XV) | 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 |
合成路线2
该中间体在本合成路线中的序号：(III)The reaction of adenosine (I) 2-acetoxyisobutyryl bromide (A) in acetonitrile/water gives a mixture of the 3-bromo (II) and 2-bromo nucleosides (III), which is treated with Dowex (OH), Amberlite (OH) or methanolic NaOMe to yield the epoxide (IV). Finally, this compound is reduced with LiEt3BH in THF/DMSO or LiAlH4 in THF to afford a mixture of the 2'-deoxy nucleoside (V) and the target compound that are separated by chromatography. Alternatively, the mixture of the nucleosides (II) and (III) is debrominated by reaction with Bu3SnH and AIBN in refluxing toluene to give the same mixture of (V) and the target compound that is separated as before.
| 【1】 Russell, A.F.; et al.; Reactions of 2-acyloxyisobutyryl halides with nucleosides. II. Reactions of adenosine. J Am Chem Soc 1973, 95, 12, 4025. |
| 【2】 Hansske, F.; Robins, M.J.; Regiospecific and stereoselective conversion of ribonucleosides to 3'-deoxynucleosides. A high yield three-stage synthesis of cordycepin from adenosine. Tetrahedron Lett 1985, 26, 36, 4295. |
| 【3】 Bazin, H.; Chattopadhyaya, J.; A convenient preparation of 3'-deoxyadenosine (cordycepin) and 9-[3'(R)-deuterio-beta-D-2'(R)-pentofuranosyl]-adenine. Synthesis 1985, 1108. |
| 【4】 Robins, M.J.; et al.; Nucleic acid related compounds. 88. Efficient conversions of ribonucleosides into their 2',3'-anhydro, 2'(and 3')-deoxy, 2',3'-didehydro-2',3'-dideoxy, and 2',3'-dideoxynucleoside analogues. J Org Chem 1995, 60, 24, 7902. |
| 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) | 48061 | 1-[3-(2,3-dihydro-1H-inden-5-yloxy)-2-[(2-methoxyethoxy)methyl]-3-oxopropyl]cyclopentanecarboxylic acid | C22H30O6 | 详情 | 详情 | |
| (V) | 49213 | [(1S,2R,4R,5R)-4-(6-amino-9H-purin-9-yl)-3,6-dioxabicyclo[3.1.0]hex-2-yl]methanol | C10H11N5O3 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)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 |