A versatile access to calystegine analogues as potential glycosidases inhibitors.
An efficient metathetic strategy and nitrone chemistry have been suitably tethered to construct 8-azabicyclo[3.2.1]octanes as versatile precursors for the synthesis of several calystegine analogues. This synthetic strategy relies on the ability of mannose-derived nitrone to undergo a highly stereoselective nucleophilic addition of various Grignard reagents to access syn orientation of alkenes, which then smoothly undergo ring-closing metathesis (RCM) to provide this framework. These RCM products 18 and 20 have been successfully used as advance precursors to synthesize many calystegine analogues (27, 36, 38, 40, 43, and 44) either by syn-dihydroxylation or by hydrogenation and followed by global deprotection. Interestingly, both compounds 36 and 40 exhibited significant noncompetitive inhibition against alpha-mannosidase and N-acetyl-beta-D-glucosaminidase.
Kaliappan
Krishna P
KP
Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400 076, India. kpk@chem.iitb.ac.in
Das
Prasanta
P
Chavan
Sanjay T
ST
Sabharwal
Sushma G
SG
D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005959:Glucosidases / Q000037:antagonists & inhibitors; D005962:Glucosylceramidase / Q000037:antagonists & inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D009662:Nortropanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D009662:Nortropanes; D005959:Glucosidases; D006026:Glycoside Hydrolases; D005962:Glucosylceramidase