Bioorganic & Medicinal Chemistry 2011-11-15

Synthesis of anomeric 1,5-anhydrosugars as conformationally locked selective α-mannosidase inhibitors.

Rajendra S Mane, Sougata Ghosh, Shailza Singh, Balu A Chopade, Dilip D Dhavale

Index: Bioorg. Med. Chem. 19(22) , 6720-5, (2011)

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Abstract

Anomeric 1,5-anhydrosugar 2 was synthesized from d-glucose derived N-Cbz protected aminodiol 8. The key step involves, acid catalyzed hydrolysis of 1,2-acetonide group in 8 to get hemiacetal that concomitantly undergoes formation of the pyranose ring by attack of C-3 hydroxyethyl group on anomeric C-1, leading to the formation of dioxabicyclo[3.2.1]octane skeleton which on hydrogenolyis gave 2. The glycosidase inhibitory activities of hydroxy- and amino-substituted anomeric 1,5-anhydrosugars 1 and 2, respectively, showed selective inhibition of α-mannosidase. These results were substantiated by molecular docking studies using WHAT IF software and AUTODOCK 4.0 program.Copyright © 2011 Elsevier Ltd. All rights reserved.