- Highly efficient and versatile synthesis of libraries of constrained β- strand mimetics
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The general approach of using a bicyclic template to produce inhibitors of the protease superfamily of enzymes has been investigated. The Diels- Alder cycloaddition reaction on solid support has been found to be highly efficient for the synthesis of libra
- Ogbu, Cyprian O.,Qabar, Maher N.,Boatman, P. Douglas,Urban, Jan,Meara, Joseph P.,Ferguson, Mark D.,Tulinsky, John,Lum, Chris,Babu, Suresh,Blaskovich, Mark A.,Nakanishi, Hiroshi,Ruan, Fuqiang,Cao, Bolong,Minarik, Ryan,Little, Tom,Nelson, Sherry,Nguyen, Minh,Gall, Anna,Kahn, Michael
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Read Online
- BETULIN DERIVED COMPOUNDS USEFUL AS ANTIBACTERIAL AGENTS
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The invention relates to compouns derived from betulin, and to the use thereof as antibacterial agents in pharmaceutical and cosmetic applications.
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Page/Page column 69
(2008/06/13)
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- 1-Azafagomine: A hydroxyhexahydropyridazine that potently inhibits enzymatic glycoside cleavage
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(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.
- Bols, Mikael,Hazell, Rita G.,Thomsen, Ib B.
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p. 940 - 947
(2007/10/03)
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