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【结 构 式】 
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【分子编号】55506 【品名】(2R,3R,5S)-5-[(acetyloxy)methyl]-2-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate 【CA登记号】 |
【 分 子 式 】C14H16N4O6 【 分 子 量 】336.3044 【元素组成】C 50% H 4.8% N 16.66% O 28.54% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of inosine (I) with trimethyl orthoacetate and AcOH, followed by a treatment with acetyl bromide, gives 3'-beta-bromo-3'-deoxyinosine (II), which is debrominated by means of Bu3SnH and AIBN in toluene to yield 3'-deoxyinosine (III). The reaction of (III) with SOCl2 /DMF in refluxing dichloromethane or with POCl3 /TEA in refluxing acetonitrile yields the 6-chloropurine (IV), which is deacetylated with NaOMe in methanol to afford the dihydroxy compound (V). The selective tritylation of the primary OH group of (V) with Tr-Cl and collidine in acetonitrile provides the trityl ether (VI), which is fluorinated with diethylaminosulfur trifluoride (DAST) and pyridine in dichloromethane to give the 3'-beta-fluoro derivative (VII). The reaction of (VII) with ammonia in THF gives the tritylated fluoroadenosine (VIII), which is finally deprotected with HCl in methanol/water to provide the target lodenosine. Alternatively, conversion of (VII) into lodenosine can be performed by first removal of the trityl protecting group with HCl in MeOH/toluene yielding compound (IX), whose chlorine atom is finally displaced with ammonia in MeOH/toluene
| 【1】 Takamatsu, S.; et al.; 9-(2,3-Dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) via a purine 3'-deoxynucleoside. J Org Chem 2001, 66, 22, 7469. |
| 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) | 38013 | 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | C10H12N4O5 | 详情 | 详情 | |
| (II) | 55505 | [(2R,3S,4S,5R)-4-(acetyloxy)-3-bromo-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H15BrN4O6 | 详情 | 详情 | |
| (III) | 55506 | (2R,3R,5S)-5-[(acetyloxy)methyl]-2-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C14H16N4O6 | 详情 | 详情 | |
| (IV) | 55507 | [(2S,4R,5R)-4-(acetyloxy)-5-(6-chloro-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H15ClN4O5 | 详情 | 详情 | |
| (V) | 48720 | (2R,3R,5S)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3-furanol | C10H11ClN4O3 | 详情 | 详情 | |
| (VI) | 48721 | (2R,3R,5S)-2-(6-chloro-9H-purin-9-yl)-5-[(trityloxy)methyl]tetrahydro-3-furanol | C29H25ClN4O3 | 详情 | 详情 | |
| (VII) | 48722 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl trityl ether; 6-chloro-9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purine | C29H24ClFN4O2 | 详情 | 详情 | |
| (VIII) | 29876 | 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-ylamine; 9-[(2R,3S,5S)-3-fluoro-5-[(trityloxy)methyl]tetrahydro-2-furanyl]-9H-purin-6-amine | C29H26FN5O2 | 详情 | 详情 | |
| (IX) | 17712 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methanol | C10H10ClFN4O2 | 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 inosine (I) with trimethyl orthoacetate and HOAc, followed by a treatment with acetyl bromide, gives 3'-beta-bromo-3'-deoxyinosine (II), which is debrominated by means of Bu3SnH and AIBN in toluene to yield 3'-deoxyinosine (III). The reaction of (III) with SOCl2 /DMF in refluxing dichloromethane or with POCl3 /TEA in refluxing acetonitrile yields the 6-chloropurine (IV), which is regioselectively monodeacetylated with TEA in methanol to afford the hydroxy compound (V). The fluorination of (V) with morpholinosulfur trifluoride (MOST) and pyridine in dichloromethane gives the 3'-beta-fluoro derivative (VI), which is finally deprotected with ammonia in THF to provide the target lodenosine.
| 【1】 Takamatsu, S.; et al.; 9-(2,3-Dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) via a purine 3'-deoxynucleoside. J Org Chem 2001, 66, 22, 7469. |
| 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) | 38013 | 9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | C10H12N4O5 | 详情 | 详情 | |
| (II) | 55505 | [(2R,3S,4S,5R)-4-(acetyloxy)-3-bromo-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H15BrN4O6 | 详情 | 详情 | |
| (III) | 55506 | (2R,3R,5S)-5-[(acetyloxy)methyl]-2-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C14H16N4O6 | 详情 | 详情 | |
| (IV) | 55507 | [(2S,4R,5R)-4-(acetyloxy)-5-(6-chloro-9H-purin-9-yl)tetrahydro-2-furanyl]methyl acetate | C14H15ClN4O5 | 详情 | 详情 | |
| (V) | 55509 | [(2S,4R,5R)-5-(6-chloro-9H-purin-9-yl)-4-hydroxytetrahydro-2-furanyl]methyl acetate | C12H13ClN4O4 | 详情 | 详情 | |
| (VI) | 55508 | [(2S,4S,5R)-5-(6-chloro-9H-purin-9-yl)-4-fluorotetrahydro-2-furanyl]methyl acetate | C12H12ClFN4O3 | 详情 | 详情 |