Deoxyiminoalditols from aldonolactones--V. Preparation of the four stereoisomers of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three 1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.
The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-amino-5-deoxy-1,5-lactams, 2, 8, 12 and 17, respectively. Reduction of the lactam function using sodium borohydride/acetic or trifluoroacetic acid, or borane dimethyl sulfide complex yielded the iminopentitols. The compounds 3, 9, 13 and 18, together with the three 1,5-dideoxy-1,5-iminoheptitols 19,20 and 21 were tested for inhibition of the glycosidase activities present in an extract from human liver. Compound 18 was a potent and 19 a moderately good inhibitor of beta-glucosidase. Compound 3 together with 19, 20 and 21, all having D-arabino-configuration at the hydroxy-substituted carbon atoms, were good inhibitors of alpha-L-fucosidase.
Godskesen
M
M
Department of Organic Chemistry, Technical University of Denmark, Lyngby, Denmark.
Lundt
I
I
Madsen
R
R
Winchester
B
B
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D005069:Evaluation Studies as Topic; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D013402:Sugar Alcohols / Q000138:chemical synthesis*
D004791:Enzyme Inhibitors; D007783:Lactones; D013402:Sugar Alcohols; D006026:Glycoside Hydrolases