ISSN:
0947-6539
Keywords:
chemoselectivity
;
enzyme inhibitors
;
glycosidases
;
kinetics
;
pyridazines
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
(3,4-trans-4,5-trans)-4,5-dihydroxy-3-hydroxymethylhexahydropyrida-zine (16) was synthesized in four steps from 2,4-pentadienol (22) and 4-phenyl-triazolin-3,5-dione (18) in an overall yield of 32%. In the first step a Diels-Alder reaction between 18 and 22 gave (π)-2-hydroxymethyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]non-3-ene-7,9-dione (23c) in 88% yield. Epoxidation of 23c with trifluoromethyl(methyl)dioxirane, generated in situ, gave the trans epoxide 24c in 62% yield. Hydrolysis of the epoxide with perchloric acid gave stereoselectively (2,3-trans-3,4-trans)-3,4-dihydroxy-2-hydroxy-methyl-8-phenyl-1,6,8-triazabicyclo[4.3.0]-nonane-7,9-dione (26) in 73% yield. In the fourth and final step, hydrazinolysis of 26 gave 16 in 84% yield. Pyridazine 16 was found to be a potent inhibitor of α-and β-glucosidase, isomaltase and glyco-gen phosphorylase, while galactosidases and α-mannosidase were not inhibited. The inhibition of β-glucosidase is independent of pH, and was found to be due to unprotonated 16.
Additional Material:
3 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/chem.19970030616
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