Aziridine carboxylate from D-glucose: synthesis of polyhydroxylated piperidine, pyrrolidine alkaloids and study of their glycosidase inhibition.
The D-glucose derived aziridine carboxylate 5 was obtained from (E)-ethyl-6-bromo-1,2-O-isopropylidene-3-O-benzyl-5-deoxy-alpha-D-xylo-5-eno-heptofuranuronate 4 through conjugate addition of benzylamine and in situ intramolecular nucleophilic expulsion of bromine. The regioselective aziridine ring-opening, using water as a nucleophile, resulted in the alpha-hydroxy-beta-aminoester 6, which was exploited in the synthesis of six and five membered azasugars 1b/1c and 2b/2c, respectively. The glycosidase inhibitory activity of the title compounds was evaluated.
Dhavale
Dilip D
DD
Garware Research Centre, Department of Chemistry, University of Pune, Pune, 411 007, India. ddd@chem.unipune.ernet.in
Kumar
K S Ajish
KS
Chaudhari
Vinod D
VD
Sharma
Tarun
T
Sabharwal
Sushma G
SG
Prakashareddy
J
J
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001388:Aziridines / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D001388:Aziridines; D004791:Enzyme Inhibitors; D010880:Piperidines; D011759:Pyrrolidines; C073440:aziridine-2-carboxylic acid; D006026:Glycoside Hydrolases; D005947:Glucose