| 崔燚,李夏冰,王伟,李宝林.化学通报,2017,80(7):661-666,687. |
| N-[3-(4-乙氧基苄基)-4-氯苯基]-1-脱氧野尻霉素的合成及其降血糖作用 |
| Synthesis and hypoglycemic effect of N-[(3-(4-ethoxybenzyl)-4-chlorophenyl]-1-deoxynojirimycin |
| 投稿时间：2017-01-10 修订日期：2017-02-08 |
| DOI： |
| 中文关键词: 脱氧野尻霉素 坎格列净 血糖 尿糖 降血糖 |
| 英文关键词:1-deoxynojirimycin, canagliflozin, blood glucose, urine glucose, decrease blood glucose |
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| 中文摘要: |
| 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,设计并合成了新化合物N-[3-(4-乙氧基苄基)-4-氯苯基]-1-脱氧野尻霉素(A)。该化合物以2-氯-5-硝基苯甲酸为起始原料,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,合成了中间体化合物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。为进行化合物A的纯化,将粗品与乙酸酐反应,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)。经化合物B水解制得纯的化合物A。当将合成的化合物A以口服方式给SD大鼠后,通过测定血糖、尿量和尿糖,发现该化合物可以降低SD大鼠血糖,增加葡萄糖从尿液中的排出。 |
| 英文摘要: |
| By using dapagliflozin, canagliflozin and 1-deoxynojirimycin, which can be used to reduce blood glucose, as the references, the target compound N-[(3-(4-ethoxybenzyl)-4-chlorophenyl]-1-deoxynojirimycin (A) was firstly designed and synthesized. Herein 2-chloro-5-nitro benzoic acid was used as the starting material to obtain 2-chloro-5-amino-4′-ethoxy diphenyl methane as an intermediate 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. To purify A, the crude A was treated with acetic anhydride to yield tetraacetyl N-[(3-(4-ethoxybenzyl)-4-chlorophenyl]-1-deoxynojirinmycin (B). Pure B was obtained by the isolation of column chromatography. Then the hydrolyzation of B gave the pure compound A. By measuring blood glucose, urine volume and urine glucose after dosing orally the synthesized compound A to SD rats, it was found that the compound A can effectively decrease the SD rats’ blood glucose, increase urine volume and the excretion of urine glucose. |
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