Medicinal scientific study based on imiosugar C-glycosides mimics

糖苷酶和糖基转移酶参与广泛的合成代谢和分解代谢过程，包括消化、糖缀合物的溶酶体催化、糖蛋白生物合成。因此，从治疗的角度来看，使用抑制剂在体内修饰或阻断这些过程是一个非常感兴趣的话题。亚氨基糖是其中内环氧被碱性氮原子取代的糖。它们被认为是某些类型的酶反应中的过渡态模拟物。这使得作为碳水化合物模拟物的亚氨基糖领域成为一个令人兴奋的研究领域。以不对称烯丙基烷基化、RCM和Negishi交叉偶联为关键反应，实现了α-1-C-烷基阿拉伯亚氨基呋喃糖的不对称合成。令人惊讶的是，L-型对大鼠肠道麦芽糖酶显示出相当强的抑制活性，而D-型的活性要弱得多。一些制备的L-型显示出对肠麦芽糖酶的有效抑制活性，其IC 50值与用于治疗2型糖尿病的商业药物如阿卡波糖、伏格列波糖和米格列醇的IC 50值相当。其中，α-1-C-L-丁酰氨基呋喃糖对肠道蔗糖酶的抑制活性较上述市售药物强。

Glycosidases and glycosyltransferases are involved in a wide range of anabolic and catabolic process, including digestion, the lysosomal catabolism of glycoconjugates, glycoprotein biosynthesis. Hence, modifying or blocking these processes in vivo using inhibitors is a topic of great interest from the therapeutic point of view. Iminosugars are sugars in which the endocyclic oxygen is replaced by a basic nitrogen atom. They are regarded as transition state mimics in certain types of enzyme reactions. This makes the field of iminosugars as carbohydrate mimics an exciting area of research. The asymmetric synthesis of α-1-C-alkyl-arabinoiminofuranoses was achieved by asymmetric allylic alkylation, RCM, and Negishi cross coupling as key reactions. Surprisingly, the L-forms showed a quite potent inhibitory activity toward rat intestinal maltase, while the activities of the D-forms were much weaker. Some of the prepared L-forms showed potent inhibitory activities towards intestinal maltase, with IC50 values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity towards intestinal sucrase of α-1-C-L-butylarabinoiminofuranose was quite strong towards intestinal sucrase compared to the above commercial drugs.