Synthesis and evaluation of the glycosidase inhibitory activity of 5-hydroxy substituted isofagomine analogues.
An efficient strategy for the synthesis of 5-hydroxy substituted isofagomine analogues and , having both -CH2OH/CH3 and -OH functionality at the C-5 position, and evaluation of their inhibitory potency is reported. The synthetic methodology involves the aldol-Cannizzaro reaction of easily available alpha-d-xylopentodialdose followed by hydrogenolysis to afford the triol . Selective amidation of the alpha- and beta-hydroxymethyl group at C-4, deprotection of the 1,2-acetonide group and hydrogenation gave the target molecules, which were found to be potent against beta-glycosidases with IC50 values in the micro molar range. Compound showed excellent potency against glycosidases and human salivary amylase.
Matin
Mohammed M
MM
Garware Research Centre, Department of Chemistry, University of Pune, Pune 411 007, India.
Sharma
Tarun
T
Sabharwal
Sushma G
SG
Dhavale
Dilip D
DD
D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D050112:Imino Pyranoses / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared
D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; D010880:Piperidines; C098432:isofagomine; D006026:Glycoside Hydrolases