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以具有降血糖活性的达格列净、卡格列净和脱氧野尻霉素为参照,设计合成了新化合物N-[3-(4-乙氧基苄基)-4-氯苯基]-1-脱氧野尻霉素(A)。以2-氯-5-硝基苯甲酸为原料,先将羧酸转化为酰氯、再经Friedel-Crafts酰基化、羰基还原及硝基还原,合成了中间体2-氯-5-氨基-4’-乙氧基二苯基甲烷;另一方面,以单丙酮葡萄糖为原料,经选择性氧化和水解反应得到5-氧化-D-葡萄糖。该化合物和2-氯-5-氨基-4’-乙氧基二苯基甲烷发生双还原胺化反应得到化合物A的粗品。将粗品A与乙酸酐反应,经柱色谱分离得到高纯度的四乙酰基-N-[3-(4-乙氧基苄基)-4-氯苯基]-1-脱氧野尻霉素(B),再将其水解制得纯的化合物A。将化合物A口服给药SD大鼠后,发现该化合物可以降低SD大鼠血糖,增加尿量和葡萄糖从尿液中的排出。
A new compound named N- [3- (4-ethoxybenzyl) -4-chlorophenyl] - isoflurane was designed and synthesized by using dapagliflozin, 1-Deoxynojirimycin (A). Starting from 2-chloro-5-nitrobenzoic acid, the carboxylic acid was first converted to acid chloride. After Friedel-Crafts acylation, carbonyl reduction and nitro reduction, the intermediate 2-chloro-5-amino-4 ’- ethoxydiphenylmethane; on the other hand, monoacetone glucose is used as a raw material to obtain 5-oxo-D-glucose by selective oxidation and hydrolysis. This compound and 2-chloro-5-amino-4’-ethoxydiphenylmethane undergo double reductive amination to give the crude compound A. The crude product A was reacted with acetic anhydride and separated by column chromatography to obtain high purity of tetraacetyl-N- [3- (4-ethoxybenzyl) -4-chlorophenyl] -1-deoxynojirimycin ), Which is then hydrolyzed to give pure Compound A. Compound A was administered orally to SD rats and found to reduce blood glucose, increase urine output, and excretion of glucose from urine in SD rats.