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.%By using hypoglycemic drugs dapagliflozin,canagliflozin and 1-deoxynojirimycin as reference,the target compound N-[(3-(4-ethoxybenzyl)-4-chlorophenyl]-1-deoxynojirimycin (A) was firstly designed and synthesized.Herein,the intermediate 2-chloro-5-amino-4'-ethoxy diphenyl methane was prepared from 2-chloro-5-nitro benzoic acid through a synthetic route including chlorination of carboxylic acid,Friedel-Crafts acylation,reduction of carbonyl and reduction of nitro.On the other hand,5-keto-D-glucose was gotten from 1,2-O-isopropylidene-D-glucofuranose by selective oxidation and hydrolysis.The crude A was obtained by the double reductive amination of 2-chloro-5-amino-4'-ethoxy diphenyl methane and 5-keto-D-glucose.The crude A was treated with acetic anhydride to yield tetraacetyl N-[(3-(4-ethoxybenzyl)-4-chlorophenyl]-1-deoxynojirinmycin(B).B was purified by column chromatography.Then the hydrolyzation of B gave the pure compound A.It was found that the compound A can effectively decrease the SD rats' blood glucose,increase urine volume and the excretion of urine glucose after dosing orally the compound A to SD rats.
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