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【结 构 式】 
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【分子编号】37778 【品名】(nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone 【CA登记号】21272-85-5 |
【 分 子 式 】C7H7NO4S 【 分 子 量 】201.20292 【元素组成】C 41.79% H 3.51% N 6.96% O 31.81% S 15.94% |
合成路线1
该中间体在本合成路线中的序号：(IV)A new enantioselective synthesis of neplanocin A has been reported: The enantiocontrolled condensation of the 6-chloropurine (I) with cis-1,3-bis(benzoyloxy)-4-cyclopentene (II) catalyzed by a chiral Pd catalyst gives the alkylated purine (III), which is condensed with the nitrosulfone (IV) by means of PPh3 and TEA yielding the intermediate (V). Epoxidation of (V) with MCPBA in dichloromethane affords the epoxide (VI), which is oxidized with O3 and DBU in methanol/THF giving the cyclopentenecarboxylate (VII). The esterification of the beta-OH group of (VII) with 4-nitrobenzoic acid (VIII), PPh3 and DEAD in THF, using a Mitsunobu reaction to invert the OH group, yields the ester (IX), with the desired alpha-OH configuration. The reduction of (IX) with DIBAL in THF/dichloromethane affords the unsaturated the diol (X), which is dihydroxylated with OsO4 and NMO in acetone/water providing the tetraol (XI). The reaction of (XI) with 2,2-dimethoxypropane and TsOH gives the diacetonide (XII), which is selectively monodeprotected with FeCl3 on silica gel yielding the dihydroxylated acetonide (XIII). The regioselective hydroxylation of the primary OH of (XIII) with pivaloyl chloride (Piv-Cl) in pyridine yields the pivalate (XIV), which is dehydrated with SOCl2 in DMF/pyridine affording the fully protected 6-chloropurine derivative (XV). Compound (XV) is treated with ammonia in order to eliminate the pivaloyl group and to form the adenine derivative (XVI), which is finally treated with hot aqueous HCl to eliminate the acetonide group.
| 【1】 Madsen, R.; Brown, B.; Guile, S.D.; Trost, B.M.; Palladium-catalyzed enantioselective synthesis of carbanucleosides. J Am Chem Soc 2000, 122, 25, 5947. |
| 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) | 17692 | 6-Chloropurine; 6-chloro-9H-purine | 87-42-3 | C5H3ClN4 | 详情 | 详情 |
| (II) | 37776 | (1R,4S)-4-(benzoyloxy)-2-cyclopenten-1-yl benzoate | C19H16O4 | 详情 | 详情 | |
| (III) | 41036 | (1S,4R)-4-(6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl benzoate | C17H13ClN4O2 | 详情 | 详情 | |
| (IV) | 37778 | (nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone | 21272-85-5 | C7H7NO4S | 详情 | 详情 |
| (V) | 41037 | 6-chloro-9-[(1R,4S)-4-[(S)-nitro(phenylsulfonyl)methyl]-2-cyclopenten-1-yl]-9H-purine; (S)-[(1S,4R)-4-(6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl](nitro)methyl phenyl sulfone | C17H14ClN5O4S | 详情 | 详情 | |
| (VI) | 41038 | (S)-[(1S,2S,4R,5R)-4-(6-chloro-9H-purin-9-yl)-6-oxabicyclo[3.1.0]hex-2-yl](nitro)methyl phenyl sulfone; 6-chloro-9-[(1R,2R,4S,5S)-4-[(S)-nitro(phenylsulfonyl)methyl]-6-oxabicyclo[3.1.0]hex-2-yl]-9H-purine | C17H14ClN5O5S | 详情 | 详情 | |
| (VII) | 41039 | methyl (3S,4R)-4-(6-chloro-9H-purin-9-yl)-3-hydroxy-1-cyclopentene-1-carboxylate | C12H11ClN4O3 | 详情 | 详情 | |
| (VIII) | 18119 | 4-nitrobenzoic acid; p-nitrobenzoic acid | 62-23-7 | C7H5NO4 | 详情 | 详情 |
| (IX) | 41040 | (1R,5R)-5-(6-chloro-9H-purin-9-yl)-3-(methoxycarbonyl)-2-cyclopenten-1-yl 4-nitrobenzoate | C19H14ClN5O6 | 详情 | 详情 | |
| (X) | 41041 | (1R,5R)-5-(6-chloro-9H-purin-9-yl)-3-(hydroxymethyl)-2-cyclopenten-1-ol | C11H11ClN4O2 | 详情 | 详情 | |
| (XI) | 41042 | (1S,2S,3S,4R)-4-(6-chloro-9H-purin-9-yl)-1-(hydroxymethyl)-1,2,3-cyclopentanetriol | C11H13ClN4O4 | 详情 | 详情 | |
| (XII) | 41043 | C17H21ClN4O4 | 详情 | 详情 | ||
| (XIII) | 41044 | (3aS,4S,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-4-(hydroxymethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol | C14H17ClN4O4 | 详情 | 详情 | |
| (XIV) | 41045 | [(3aS,4S,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-4-hydroxy-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl pivalate | C19H25ClN4O5 | 详情 | 详情 | |
| (XV) | 41046 | [(3aR,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methyl pivalate | C19H23ClN4O4 | 详情 | 详情 | |
| (XVI) | 41047 | [(3aR,6R,6aS)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-6,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]methanol | C14H17N5O3 | 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 enantiocontrolled condensation of the protected guanine (I) with cis-1,3-bis(benzoyloxy)-4-cyclopentene (II) catalyzed by a chiral Pd catalyst gives the alkylated guanine (III), which is condensed with the nitrosulfone (IV) by means of PPh3 and TEA to yield the intermediate (V). The oxidation of (V) with oxone, tetramethylguanidine, and Na2CO3 in methanol/dichloromethane affords the cyclopentenecarboxylate (VI), which is finally reduced with calcium borohydride and deprotected with ammonia to provide the target compound.
| 【1】 Madsen, R.; Brown, B.; Guile, S.D.; Trost, B.M.; Palladium-catalyzed enantioselective synthesis of carbanucleosides. J Am Chem Soc 2000, 122, 25, 5947. |
| 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) | 37775 | 2-(acetamido)-9H-purin-6-yl diphenylcarbamate | C20H16N6O3 | 详情 | 详情 | |
| (II) | 37776 | (1R,4S)-4-(benzoyloxy)-2-cyclopenten-1-yl benzoate | C19H16O4 | 详情 | 详情 | |
| (III) | 37777 | (1S,4R)-4-(2-(acetamido)-6-[[(diphenylamino)carbonyl]oxy]-9H-purin-9-yl)-2-cyclopenten-1-yl benzoate | C32H26N6O5 | 详情 | 详情 | |
| (IV) | 37778 | (nitromethyl)(dioxo)phenyl-lambda(6)-sulfane; nitromethyl phenyl sulfone | 21272-85-5 | C7H7NO4S | 详情 | 详情 |
| (V) | 37779 | 2-(acetamido)-9-[(1R,4S)-4-[(S)-nitro(phenylsulfonyl)methyl]-2-cyclopenten-1-yl]-9H-purin-6-yl diphenylcarbamate | C32H27N7O7S | 详情 | 详情 | |
| (VI) | 37780 | methyl (1S,4R)-4-(2-(acetamido)-6-[[(diphenylamino)carbonyl]oxy]-9H-purin-9-yl)-2-cyclopentene-1-carboxylate | C27H24N6O5 | 详情 | 详情 |