Ranirestat, SX-3202((+)-(S)-isomer), SX-3030(racemate), AS-3201, SX-3201-药物合成数据库

【药物名称】Ranirestat, SX-3202((+)-(S)-isomer), SX-3030(racemate), AS-3201, SX-3201

化学结构式(Chemical Structure):

参考文献No.	476319
标题:	Novel, highly potent aldose reductase inhibitors: (R)-(-)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3'-pyrrolidine-1,2',3,5'-tetrone (AS-3201) and its congeners
作者:	Negoro, T.; Murata, M.; Ueda, S.; Fujitani, B.; Ono, Y.; Kuromiya, A.; Komiya, M.; Suzuki, M.; Matsumoto, J.
来源:	J Med Chem 1998,41(21),4118-29

合成路线图解说明: The alkylation of ethyl 2-(benzyloxycarbonylamino)cyanoacetate (I) with ethyl bromoacetate and anhydrous potassium carbonate in acetone gives diethyl 2-(benzyloxycarbonylamino)-2-cyanosuccinate (II), which is hydrolyzed by means of hydrogen peroxide and sodium carbonate in acetone/water, yielding 3-(benzyloxycarbonylamino)-3-(ethoxycarbonyl)pyrrolidine-2,5-dione (III). Racemic (III) is then resolved by means of crystallization with cinchonidine in ethanol to give the (-)-enantiomer (IV) (>99.5% e.e.). Hydrogenolysis of (IV) over Pd/C in ethanol, followed by treatment with 2,5-dimethoxytetrahydrofuran in acetic acid, affords (-)-3-(ethoxycarbonyl)-3-(pyrrol-1-yl)pyrrolidine-2,5-dione (VI). Treatment of (VI) with trichloroacetyl chloride in ethyl acetate, followed by condensation with 4-bromo-2-fluorobenzylamine in the presence of triethylamine, gives AS-3201 (>99.4% e.e.).

参考文献No.	566373
标题:	AS-3201
作者:	Negoro, T.; Komiya, M.; Ono, Y.
来源:	Drugs Fut 2000,25(2),131

合成路线图解说明: The alkylation of ethyl 2-(benzyloxycarbonylamino)cyanoacetate (I) with ethyl bromoacetate and anhydrous potassium carbonate in acetone gives diethyl 2-(benzyloxycarbonylamino)-2-cyanosuccinate (II), which is hydrolyzed by means of hydrogen peroxide and sodium carbonate in acetone/water, yielding 3-(benzyloxycarbonylamino)-3-(ethoxycarbonyl)pyrrolidine-2,5-dione (III). Racemic (III) is then resolved by means of crystallization with cinchonidine in ethanol to give the (-)-enantiomer (IV) (>99.5% e.e.). Hydrogenolysis of (IV) over Pd/C in ethanol, followed by treatment with 2,5-dimethoxytetrahydrofuran in acetic acid, affords (-)-3-(ethoxycarbonyl)-3-(pyrrol-1-yl)pyrrolidine-2,5-dione (VI). Treatment of (VI) with trichloroacetyl chloride in ethyl acetate, followed by condensation with 4-bromo-2-fluorobenzylamine in the presence of triethylamine, gives AS-3201 (>99.4% e.e.).