N-苄基脱氧野尻霉素的合成及其对α-葡萄糖苷酶的抑制活性

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• 英文论文题名：Synthesis of N-benzyl deoxynojirimycin and its inhibition on α-glucosidase
• 论文作者：曾凡新 ; 卢桃 ; 林萍 ; 彭大勇 ; 尹忠平
• 英文论文作者：Zeng Fanxin ; Lu Tao ; Lin Ping ; Peng Dayong ; Yin Zhongping ; Key Laboratory of Natural Product Research and Development ; College of Food Sciences and Engineering ; Jiangxi Agricultural University
• 年：2016
• 作者机构：江西省天然产物与功能食品重点实验室;江西农业大学食品科学与工程学院;
• 论文关键词：N-苄基脱氧野尻霉素 ; α-葡萄糖苷酶抑制剂 ; 合成
• 英文论文关键词：n-benzyl deoxynojirimycin ; α-glucosidase inhibitor ; synthesis
• 会议召开时间：2016-11-09
• 会议录名称：中国食品科学技术学会第十三届年会论文摘要集
• 英文会议录名称：Abstracts of the 13th Annual Meeting of CIFST
• 语种：中文
• 分类号：R914.5;TS201.2
• 学会代码：ZGSP
• 会议名称：中国食品科学技术学会第十三届年会
• 会议地点：中国北京
• 主办单位：中国食品科学技术学会
• 学会名称：中国食品科学技术学会
• 页数：2
• 文件大小：115k
• 原文格式：O
• 会议级别：全国

摘要

α-葡萄糖苷酶是体内糖类消化的关键酶之一,抑制其活性可有效地抑制餐后血糖升高,服用α-葡萄糖苷酶抑制剂是Ⅱ型糖尿病治疗的首选方法之一。从桑根皮中分离得到的1-脱氧野尻霉素(1-Deoxynojirimycin,1-DNJ)是具有与α-1,4-葡萄糖苷键类似结构的氨基糖类,这种多羟基生物碱及其衍生物对α-葡萄糖苷酶有较强的抑制作用,其中N-羟乙基-1-脱氧野尻霉素(米格列醇)目前为治疗2型非胰岛素依赖型糖尿病的强效药物,N-丁基-1-脱氧野尻霉素(美格鲁特)为高雪氏症口服药物。脱氧野尻霉素衍生物在临床医学上的成功应用激起许多研究者的兴趣,使其成为近几年的研究热点。本文以四苄基葡萄糖为原料,经氢化锂铝开环成醇,swern氧化成醛,再经还原氨化,得到四苄基1-脱氧野尻霉素,然后在其N-位上引入多种苄基衍生物,在氢气钯碳下脱掉保护基团后,最终合成14个结构新颖的1-脱氧野尻霉素衍生物(其结构已经~1H NMR、MS确证)。体外α-葡萄糖苷酶活性检测结果表明,当浓度达500μM时,所合成的14个1-脱氧野尻霉素衍生物均对α-葡萄糖苷酶表现出了较强的抑制活性,其中苯环上取代基为溴原子时抑制效果最佳,且抑制率可达22.45%,为进一步开发新型降糖活性功能因子提供理论基础。
α-Glucosidase is one of the key enzymes involved in the carbohydrate metabolism.Decreasing the action of a-glucosidase can effectively suppress postprandial hyperglycemia,and the clinical use of drug-inhibitors has been the preferred method for the treatment of type 2 diabetes.The 1-deoxynojirimycin(1-DNJ) was isolated from the roots of mulberry trees and discovered as the first natural glucose mimic with α-1,4 glycosidic bond.The polyhydroxylated piperidine alkaloid and its derivatives have been shown to possess potent inhibitory activity of α-glucosidase,such as N-hydroxyethyl-1-DNJ(Miglitol),which is an oral drug for the treatment of noninsulin-dependent diabetes,and N-butyl-DNJ(Zavesca),which is an oral drug for the treatment of Gaucher's disease.The therapeutic success of these molecules serves as an inspiration for many reseachers,and it have been a popular reseach spot now.In this paper,the synthesis of N-benzyl-deoxynojirimycin started with 2,3,4,6-tetra-0-benzyl-α-glucopyranose.Protected 1-deoxynojirimycin was prepared by a successive hemiacetal reduction with lithium aluminum hydride /swern oxidation /double reductive amination sequence.Then the novel compounds obtained from the reaction of substitution and hydrogenolysis.The vitro active experimental data suggest that all the novel compounds have the inhibitory toward a-glucosidase,among them 1-(3-bromobenzyl)-2-(hydroxymethyl)piperidine-3,4,5-triol showed the stronger inhibitory than others,which can provide a theoretical basis for the further development of novel functional factors with hypoglycemic activity.

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