Synthesis, computational study and glycosidase inhibitory activity of polyhydroxylated conidine alkaloids--a bicyclic iminosugar.
New bicyclic conidine iminosugars 1d and 1e were synthesized from D-glucose. Thus, D-glucose was converted to sugar beta-amino acids 3a and 3b in good yields. Individual treatment of 3a/3b with the Mukaiyama reagent afforded sugar beta-lactams 4a/4b that on reduction with LiAlH(4)/AlCl(3) gave azetidines 5a/5b with a sugar appendage. Reductive aminocyclization of sugar azetidines 5a/5b afforded the corresponding conidine iminosugars 1d/1e. Based on the (1)H NMR and DFT calculation studies the conformation of 1d was assigned as half chair A2 and that of 1e as a boat B2. The glycosidase inhibitory activities of 1d and 1e such as alpha-mannosidase, alpha-glucosidase and alpha-galactosidase were studied. The alpha-amylase activity was compared with acarbose. Compound 1d was found to be a moderate inhibitor of glycosidases while 1e was noticed to be a good inhibitor of alpha-mannosidase and a moderate inhibitor of other glycosidases. These results were substantiated by molecular docking studies using WHAT IF software and the AUTODOCK 3.0 program.
Garware Research Centre, Department of Chemistry, University of Pune, Pune-411007, India.
Shrihari P
SP
Sanap
Sougata
S
Ghosh
Amit M
AM
Jabgunde
Rahul V
RV
Pinjari
Shridhar P
SP
Gejji
Shailza
S
Singh
Balu A
BA
Chopade
Dilip D
DD
Dhavale
D000470:Alkaloids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D003198:Computer Simulation; D019277:Entropy; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006900:Hydroxylation; D050111:Imino Sugars / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D011108:Polymers / Q000737:chemistry*; D011789:Quantum Theory
D000470:Alkaloids; D004791:Enzyme Inhibitors; D050111:Imino Sugars; D011108:Polymers; C039164:conidine; D006026:Glycoside Hydrolases