新型取代苯甲胺葡萄糖氮苷的合成及其抗缺氧活性  

Synthesis and Preliminary Antihypoxic Activities of Novel Substituted Benzylamine N-glycosides

作　　者：刘文香[1,2] 李雅潇[2] 杨硕[1,2] 崔颖[2] 李霞[2] 龚海英[2] 李灵芝[2,3] 

机构地区：[1]天津医科大学,天津300070 [2]武警后勤学院药物化学教研室,天津300309 [3]天津市职业与环境危害防制重点实验室,天津300309

出　　处：《合成化学》2016年第11期929-935,共7页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(81471823);天津市重点基金资助项目(12JCZDJC34700);武警后勤学院科研创新团队项目(WHTD210303);武警后勤学院附属医院种子基金资助项目(FYQ201453);军队"2110"工程资助项目(JY2110-7)

摘　　要：以取代苯甲醛(1a^1s)为原料,通过三条路线[A:1a^1o为起始原料,经硼氢化钠还原和溴代反应制得苄基溴衍生物(3a^3o);3a^3f与邻苯丁二酰亚胺经Gabriel反应制得N-苯甲基邻苯丁二酰亚胺衍生物(4a^4f);4a^4f与水合肼反应后与D-吡喃葡萄糖反应合成了N-β-D-吡喃葡萄糖苯甲胺类化合物(6a^6f)。B:3g^3o与全乙酰化D-吡喃葡萄糖胺反应制得全乙酰化葡萄糖氮苷5g^5o;5g^5o在Me ONa-Me OH中脱除乙酰基合成了6g^6o。C:1p^1s与全乙酰化D-吡喃葡萄糖胺反应制得全乙酰化葡萄糖氮苷5p^5s;5p^5s经MeONa-Me OH脱除乙酰基合成了6p^6s]合成了19个取代苯甲胺N-β-D-吡喃葡萄糖氮苷类似物(6a^6s,其中6a,6b,6e,6f,6j,6n^6q,6s为新化合物),其结构经1H NMR和ESI-MS表征。采用MTT法研究了6a^6s对缺氧内皮细胞代谢活力的影响。结果表明:6a,6g,6h和6l的抗缺氧活性优于红景天苷。Nineteen substituted benzylamine N-glycoside analogues （6a- 6s, 6a, 6b, 6e, 6f, 6j,6n - 6q, 6s were novel compounds） were synthesized by three route （A -C）, using substituted benzaldehydes（1a -1s） as materials. A： Benzyl bromide derivatives （3a - 3o） were obtained by reduction with NaBH4 and bromination from 1a - 1o. N-phenyl phthalimide derivatives （4a - 4f） were prepared by Gabriel reaction of 3a - 3f with Pathalimide. 6a - 6f were synthesized by the reaction of 4a - 4f with N2 H4 · H2 O then with D-glucopyranose. B ： Peracetylated N-glycosides （5g - 5o） were obtained by the reaction of 3g - 3o with peracetylated D-Glucopyranosylamine. 6g - 6o were synthesized by elimination acetyl of 5g - 5o in MeONa-MeOH. C ： Peracetylated N-glycoside 5p - 5s were pre- pared by the reaction of 1p -1s with peracetylated D-Glucopyranosylamine. 6p -6s were synthesized by elimination acetyl of 5p -5s in MeONa-MeOH. The structures were characterized by 1H NMR and ESI-MS. The antihypoxic activities of 6a - 6s on EA. hy 926 were investigated by MTT assay. The resuhs indicated that 6a, 6g, 6h and 6l exhibited better antihypoxic activities than Salidroside.

关 键 词：取代苯甲醛 D-吡喃葡萄糖 氮苷类似物 合成 抗缺氧活性 红景天苷 

分 类 号：O625.6[理学—有机化学] O629.13[理学—化学]