Efficient synthesis of (+)-1,8,8a-tri-epi-swainsonine, (+)-1,2-di-epi-lentiginosine, (+)-9a-epi-homocastanospermine and (-)-9-deoxy-9a-epi-homocastanospermine from a D-glucose-derived aziridine carboxylate, and study of their glycosidase inhibitory activities.
The utility of a D-glucose-derived aziridine carboxylate was demonstrated for the synthesis of polyhydroxylated quinolizidine and indolizidine alkaloids. The chemoselective reduction of 1 followed by two-carbon homologation by the Wittig reaction afforded gamma,delta-aziridino-alpha,beta-unsaturated ester 9, which on regioselective nucleophilic aziridine ring opening either by using water as a nucleophile or hydrogenation afforded delta-lactams 11/16--true synthons for the synthesis of four structurally different iminosugars, namely quinolizidine alkaloids 5b/5c, swainsonine 6b and lentiginosine 7b analogues. Glycosidase inhibitory activities of these iminosugars were investigated.
Ajish Kumar
K S
KS
Garware Research Centre, Department of Chemistry, University of Pune, Pune, 411 007, India.
Chaudhari
Vinod D
VD
Dhavale
Dilip D
DD
D000470:Alkaloids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001388:Aziridines / Q000737:chemistry*; D005947:Glucose / Q000031:analogs & derivatives*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007212:Indolizines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D054837:Quinolizidines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D013237:Stereoisomerism; D013379:Substrate Specificity; D017026:Swainsonine / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D054836:Indolizidines
D000470:Alkaloids; D001388:Aziridines; D005947:Glucose; D006026:Glycoside Hydrolases; D007212:Indolizines; D054837:Quinolizidines; D017026:Swainsonine; C528417:9-deoxy-9a-homocastanospermine; C528416:9a-homocastanospermine; C063984:lentiginosine; C033132:aziridine; C037806:castanospermine; D054836:Indolizidines