Synthesis and α-Glucosidase and α-Amylase Inhibitory Activity Evaluation of Azido- and Aminocyclitols

• Published in: European journal of organic chemistry 2014-11, Vol.2014 (31), p.6903-6917
• Main Authors: Aydin, Gökay, Ally, Khamis, Aktaş, Fatih, Şahin, Ertan, Baran, Arif, Balci, Metin
• Format: Article
• Language: English
• Subjects: Amines; Biological activity; Carbasugars; Carbo­cycles; Cyclitols; Synthetic methods
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201402762

For the synthesis of some azido‐ and aminocyclitols, (3aRS,7aSR)‐1,3,3a,7a‐tetrahydroisobenzofuran was used as the starting material. For further functionalization of the diene unit, the diene was subjected to epoxidation reactions to give mono‐ and bisepoxides depending on the amount of m‐chloroperbenzoic acid used. The ring‐opening of the epoxide functionality with NaN3 resulted in the formation of mono‐ and bisazido cyclitols. The tetrahydrofuran ring was opened in an acid‐catalysed reaction with sulfamic acid. The reduction of azide groups to give amines provided various amino‐ and bisaminocyclitol derivatives. The inhibitory effects of 20 compounds against α‐glucosidase and α‐amylase were tested. The results indicated that some of these compounds seem to have good inhibitory activity against α‐glucosidase, and low inhibitory activity against α‐amylase. Furthermore, it was demonstrated that the number and position of azides, amines, and hydroxy groups appeared to play an important role in determining the inhibitory potency of these compounds. Aminocyclitols are found in many natural products with remarkable biological activities. The synthesis of various amino‐substituted carbasugars and their inhibitory effects against α‐glucosidase and α‐amylase are discussed.