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【结 构 式】

【分子编号】41043

【品名】 

【CA登记号】

【 分 子 式 】C17H21ClN4O4

【 分 子 量 】380.831

【元素组成】C 53.62% H 5.56% Cl 9.31% N 14.71% O 16.8%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XII)

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
Extended Information