Synthesis of polyfunctional quinolizidine alkaloids: development towards selective glycosidase inhibitors.
A highly divergent route to a variety of quinolizidine alkaloids is described. The enantiomeric precursors and utilized for the synthesis of these alkaloids were constructed stereospecifically from the PET cyclization of the corresponding acetylene tethered alpha-trimethylsilyl amine moieties and , respectively, both of which were synthesised from D-ribose. The polyhydroxy quinolizidine alkaloid was found to be a selective inhibitor of alpha-galactosidase with Ki 83.9 microM. The amine analogs , and are found to be selective and potent inhibitors of alpha-glucosidase with Ki 28, 120 and 140 microM, respectively.
Pandey
Ganesh
G
Division of Organic Chemistry, National Chemical Laboratory, Pune, 411008, India. gp.pandey@ncl.res.in
Grahacharya
Debasish
D
Shashidhara
K S
KS
Khan
M Islam
MI
Puranik
Vedavati G
VG
D017485:1-Deoxynojirimycin / Q000494:pharmacology; D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D002846:Chromatography, Affinity / Q000379:methods; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000737:chemistry; D065089:Glycoside Hydrolase Inhibitors; D012266:Ribose / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D000520:alpha-Glucosidases / Q000302:isolation & purification
D000470:Alkaloids; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D017485:1-Deoxynojirimycin; D012266:Ribose; D000520:alpha-Glucosidases; D000519:alpha-Galactosidase