新型假氮杂二糖的合成研究

Azasugars, as glycosidase inhibitors, have attracted much interest in recent years and have potential applications in the treatment of metabolic diseases, viral diseases，bacterial infections and cancers. The linkage of common monosaccharides to an azasugar by a nonhydrolyzable C-C bond is named as (pseudo) aza-C-disaccharides, which are expected to enhance their selectivity and effectiveness as inhibitors, as well as are promising substrates as selective glycosidase inhibitors and have become attractive synthetic targets for organic chemists. In this project, the cheap and commercially available glycals are taken as starting materials to easily synthesize a series of pseudo aza-C-2-disaccharides through CAN-mediated radical addition, [3+2]cycloaddition, hydrogenation, decarboxylation of quaternary ester and other chemical transformations, which are ready for further biological investigation. In addition, the reaction mechanism and selectivity issues of key [3+2]cycloaddition are expected to be well investigated to find an experiential guide for other similar reactions.

具有潜在糖苷酶抑制活性的氮杂糖类化合物近年来成为了研究的热点，在代谢性疾病、病毒感染、细菌感染以及肿瘤等疾病方面有着潜在的治疗作用。将常见的单糖物质通过不可水解的 C-C 键与氮杂糖相连，形成C-连接的（假）氮杂二糖结构，被认为是选择性糖苷酶抑制剂的理想底物，可以增强氮杂糖类物质作为抑制剂的选择性和有效性，因此成为了合成化学家的研究方向。本研究项目拟从价廉、易得的烯糖出发，发展出通过CAN 介导的自由基加成、[3+2]环加成、加氢还原以及季碳位的脱羧等化学转化策略，简便地合成出一系列2-C-连接的假氮杂二糖化合物，为进一步的生物活性筛选奠定基础。同时，对于关键[3+2]环加成的反应机制、立体选择性等方面进行深入的研究，总结出相应的规律。

具有潜在生物活性的氮杂糖类化合物近年来成为了研究的热点，在代谢性疾病、病毒感染、细菌感染以及肿瘤等疾病方面有着潜在的治疗作用。本项目研究发展了硝酸铵铈介导的自由基加成等化学转化，构建出结构新型的氮杂二糖化合物中关键C-C键，可以简便地合成出相应的氮杂二糖化合物；同时发现硝酸铵铈介导的自由基加成反应策略可以应用到新型的糖氨基酸类化合物的合成，进而合成出一系列的寡聚糖氨基酸类化合物，阐明和总结出类似反应的一般规律。上述化合物的成功制备将为氮杂糖类以及糖氨基酸类化合物的活性检测与评价奠定基础。