N-hydroxyethyl-piperidine and -pyrrolidine homoazasugars: preparation and evaluation of glycosidase inhibitory activity.
An efficient and practical strategy for the synthesis of N-hydroxyethyl-1-deoxy-homonojirimycins 4 and 5 and N-hydroxyethyl-pyrrolidine homoazasugars 6 and 7 with full stereocontrol is being reported. The key step involved is the intermolecular Michael addition of benzylamine to D-glucose derived alpha,beta-unsaturated ester 8 followed by N-alkylation with ethyl bromoacetate. Reduction with LAH, acetylation, hydrogenation and protection with -Cbz group afforded compounds 14a and 14b. Removal of 1,2-acetonide functionality, hydrogenation and deacetylation afforded N-hydroxyethyl-D-gluco-1-deoxyhomonojirimycin (4) and N-hydroxyethyl-L-ido-1-deoxyhomonojirimycin (5), respectively. Compounds 14a and 14b on acetylation followed by removal of 1,2-acetonide functionality, sodium metaperiodate oxidation, hydrogenation and deacetylation gave 1,4,5-trideoxy-1,4-imino-N-hydroxyethyl-D-arabino-hexitol (6) and 1,4,5-trideoxy-1,4-imino-N-hydroxyethyl-L-xylo-hexitol (7), respectively. The glycosidase inhibition activity of compounds 4, 5, 6, 7, 16a and 16b was evaluated using sweet almond seed as a rich source of different glycosidases.
Dhavale
Dilip D
DD
Department of Chemistry, Garware Research Centre, University of Pune, Pune-411 007, India. ddd@chem.unipune.ernet.in
Matin
Mohammed M
MM
Sharma
Tarun
T
Sabharwal
Sushma G
SG
D001372:Aza Compounds / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009005:Monosaccharides / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D010880:Piperidines / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D027861:Prunus; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology
D001372:Aza Compounds; D004791:Enzyme Inhibitors; D009005:Monosaccharides; D010880:Piperidines; D010936:Plant Extracts; D011759:Pyrrolidines; D006026:Glycoside Hydrolases