Synthesis and characterization of highly oxygenated cyclitols with a new method

Structural entities having polyhydroxylated cyclohexanoid cores are widely distributed in nature, and they have, in recent decades, attracted interest among chemists due to their significant biological properties and diverse synthetic intermediates. Cyclitols are involved in glycosidase inhibition, intercellular communication, phosphate storage, protein anchoring, etc. Therefore, glycosidase inhibitors are generally regarded as promising candidates for the development of new drugs. Carbasugars, generated by replacing the endocyclic oxygen atom in monosaccarides, are thought to be more viable drug candidates than natural sugars, since they are stable under hydrolytic conditions. In study we synthesized some new carbasugar derivatives and showed that they inhibit the activity of α-glycosidase and increase the activity of α-amylase. Furthermore, we prepared various branched carbahexopyranose derivatives, which showed strong inhibition for α-glycosidase. Firstly, exocyclic diene 166 and dien 180 were synthesied starting from cis-tetrahydrofthalitic anhydride 163 a few steps to aimed of new cyclitol derivatitives. Exocyclic diene 166 was reacted with tandem reaction of singlet oxygen to afforded new bicyclic peroxy compounds 168 and 169. Cleaveged of peroxy bonds in 168 and 169 in mild condition to have obtained branch of carbasugars cyclitol heptol 176 and 179. In study of bioligical activity, these compounds were showed inhibition for α-glycosidase and α-amylase. Dien 180 was treated with m-chloroperbenzoic acide and obtained varied of epoxy benzoat and bisepoxy 188, 201, 213, 214. The complex stereochemistry was introduced by epoxidation of the diene followed by epoxide-ring-opening reactions with sodium azide. Reduction of the azido functionalities and cleavage of the tetrahydrofuran ring with sulfamic acid gave various mono- and diaminocyclitol derivatives. The inhibitory effects of 20 compounds against α-glucosidase and α-amylase were tested. The results indicated that compounds 186, 191, 217 and 220 seem to have good inhibitory activity against α-glucosidase, and none of the synthesized compounds showed good inhibitory activity against α-amylase, except for 204 and 218. Furthermore, the study demonstrated that both the number and position of azide, amine, and hydroxy groups appears to play an important role in determining the inhibitory potency of the compound against α-glucosidase and α-amylase. Furthermore, study was noted that the ring-opening of the tetrahydrofuran, epoxy ring, bicyclic peroxy moiety results in an increased activity. These results may be used for the development of new drugs for the treatment of diseases like hyperglycemia and diabetes mellitus.