10316-50-4Relevant articles and documents
1-Azafagomine: A hydroxyhexahydropyridazine that potently inhibits enzymatic glycoside cleavage
Bols, Mikael,Hazell, Rita G.,Thomsen, Ib B.
, p. 940 - 947 (2007/10/03)
(3,4-trans-4,5-trans)-4,5-dihydroxy-3-hydroxymethylhexahydropyridazine (16) was synthesized in four steps from 2,4-pentadienol (22) and 4-phenyltriazolin-3,5-dione (18) in an overall yield of 32%. In the first step a Diels Alder reaction between 18 and 22 gave (±)-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-hydroxymethyl-8-phenyl-1,6,8-triazabicy clo[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 χ-and β-glucosidase, isomaltase and glycogen phosphorylase, while galactosidases and χ-mannosidase were not inhibited. The inhibition of β-glucosidase is independent of pH, and was found to be due to unprotonated 16.
