Isofagomine lactams, synthesis and enzyme inhibition
| Autor: | Huizhen Liu, Vinni H. Lillelund, Helmer Søhoel, Mikael Bols, Xifu Liang |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Glycoside Hydrolases Lactams Chemistry Stereochemistry Aspergillus oryzae Organic Chemistry Arabinose Biochemistry Kinetics Enzyme inhibition chemistry.chemical_compound Reaction rate constant Piperidines Lactam Thermodynamics Glycoside hydrolase Enzyme Inhibitors Physical and Theoretical Chemistry Fucose Imino Pyranoses |
| Zdroj: | Lillelund, V H, Liu, H, Liang, X, Søhoel, H & Bols, M 2003, ' Isofagomine lactams, synthesis and enzyme inhibition ', Organic & Biomolecular Chemistry, vol. 1, pp. 282-287 . |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | The synthesis of isofagomine lactams (2-oxoisofagomines) corresponding to the biologically important hexoses is presented. The D-glucose/D-mannose analogue (3S,4R,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (9) was synthesised in 9 steps from D-arabinose, the D-galactose analogue (3S,4S,5R)-3,4-dihydroxy-5-hydroxymethylpiperidin-2-one (10) was synthesised in 11 steps from D-arabinose and the L-fucose analogue (3R,4R,5R)-3,4-dihydroxy-5-methylpiperidin-2-one (11) was synthesised in 12 steps from L-arabinose. The three lactams 9-11 were found to be glycosidase inhibitors with micro- to nanomolar inhibition constants. The lactam 10 showed slow onset inhibition of beta-galactosidase from A. Oryzae. The rate constants for this process were determined to be k(on) = 2.55 x 10(4) M-1 s-1 and k(off) = 1.7 x 10(-3) s-1. The activation energies and standard thermodynamic functions were also determined. |
| Databáze: | OpenAIRE |
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