Abstract
O-Glycosides are integral part several natural products. However, the O-glycosidic bond is prone to cleavage under acidic condition and enzymatic in vivo conditions. Therefore several O-glycoside mimics were prepared to address this problem which includes S, N and C-Glycosides. These mimics generally will show similar biological activity compared to the natural compounds and thus can be considered as potential therapeutic targets. Among these glycomimetics C-Glycosides are particularly gained much interest because of their presence in number of natural products and stability under physiological conditions. Structural modification by glycosylation offers an attractive approach to increase the water solubility of polyhydroxy stilbenes. Even though C-glycosides are part of several natural products, the biological activity of C-glycoside stilbenes is not explored particularly due to rare occurrence and lack of straight forward synthetic methods. In Chapter-1 we have developed microwave assisted Heck-coupling for the synthesis of mono- and bis-C-glycoside stilbenes using C-aryl glycosides and styrenes. This method provides exclusively C-glycoside trans-stilbenes with good yields. The developed Pd-catalyzed Heck-coupling method is successfully applied to various functionalized C-glycosyl aryl iodides and differentially substituted styrenes to deliver several C-glycoside trans-stilbenes with high selectivity. Synthesis of C-2 symmetric bis-C-glycoside-trans-stilbene is also accomplished. The obtained C-glycosyl trans-stilbenes were examined for human SGLT-2 inhibitory activity. Three of the analogues have shown hSGLT-2 inhibition in micro molar range (12 to 33 µM). In Chapter-2, an improved and diversified synthesis for 4-(Phenyl-C-glycosyl)-1,2,3-triazoles was developed. The key step in the synthesis involves the copper catalyzed azide alkyne click chemistry between glycosyl azide and various substituted C-glycosylated phenyl acetylenes. Use of o-Phenylene diamine as a ligand in Copper catalyzed azide-alkyne click chemistry considerably shorten the reaction the time and allows simple purification. We have generated a small library to triazoles with broad substrate scope in terms of sugars. Interestingly each triazole analogue is having two free sugar units, one attached to the triazole nitrogen and other attached to the phenyl ring at C-4. The synthesized C-glycosylated triazole analogues were assayed for β-galactosidase and β-Galectin inhibition.