Showing papers on "Aldose published in 2000"

Aldose and aldehyde reductases: correlation of molecular modeling and mass spectrometric studies on the binding of inhibitors to the active site.

Abstract: Aldose and aldehyde reductases are monomeric NADPH-dependent oxidoreductases that catalyze the reduction of a wide variety of aldehydes and ketones to their corresponding alcohols. The overall three-dimensional structures of the enzymes are composed of similar alpha/beta TIM-barrels, and the active site residues Tyr 50, His 113, and Trp 114 interacting with the hydrophilic heads of inhibitors are conserved. We have used molecular modeling and mass spectrometry to characterize the interactions between the enzymes and three aldose reductase inhibitors: tolrestat, sorbinil, and zopolrestat. Unlike the IC(50) values (concentration of inhibitor giving 50% of inhibition in solution), the Vc(50) values measured by mass spectrometry (accelerating voltage of ions needed to dissociate 50% of a noncovalent complex in the gas phase) for the two enzymes are similar, and they correlate with the electrostatic and hydrogen-bonding energies calculated between the conserved Tyr 50, His 113, and Trp 114 and the inhibitors. The results of our comparison agree with detailed structural information obtained by X-ray crystallography, suggesting that nonconserved residues from the C-terminal loop account for differences in IC(50) values for the two enzymes. Additionally, they confirm our previous assumption that the Vc(50) values reflect the enzyme-inhibitor electrostatic and hydrogen-bonding interactions and exclude the hydrophobic interactions.

Novel MnIIMnIIIMnII Trinuclear Complexes with Carbohydrate Bridges Derived from Seven-Coordinate Manganese(II) Complexes with N-Glycoside

Abstract: Reactions of MnX2·nH2O with tris(N-(d-mannosyl)-2-aminoethyl)amine ((d-Man)3-tren), which was formed from d-mannose and tris(2-aminoethyl)amine (tren) in situ, afforded colorless crystals of [Mn((d-Man)3-tren)]X2 (3a, X = Cl; 3b, X = Br; 3c, X = NO3; 3d, X = 1/2SO4). The similar reaction of MnSO4·5H2O with tris(N-(l-rhamnosyl)-2-aminoethyl)amine ((l-Rha)3-tren) gave [Mn((l-Rha)3-tren)]SO4 (4d), where l-rhamnose is 6-deoxy-l-mannose. The structures of 3b and 4d were determined by X-ray crystallography to have a seven-coordinate Mn(II) center ligated by the N-glycoside ligand, (aldose)3-tren, with a C3 helical structure. Three d-mannosyl residues of 3b are arranged in a Δ(ob3) configuration around the metal, leading to formation of a cage-type sugar domain in which a water molecule is trapped. In 4d, three l-rhamnosyl moieties are in a Δ(lel3) configuration to form a facially opened sugar domain on which a sulfate anion is capping through hydrogen bonding. These structures demonstrated that a configurationa...

Kinetics of Equilibrium Attainment between Molecular Glycolaldehyde Structures in an Aqueous Solution

Abstract: The kinetics of the isomerization and monomerization of the glycolaldehyde dimer in a D2O solution (pD = 4.3) at 25°C is studied by1H NMR spectroscopy (360 MHz). The dynamics of the concentrations of seven dimeric and two monomeric glycolaldehyde forms present in the solution is examined when the system attains equilibrium. A kinetic scheme of equilibrium attainment in an aqueous solution of glycolaldehyde is proposed. The apparent rate constants of the transformation of the molecular glycolaldehyde structures into each other are determined

Partially Hydroxylated 2, 5‐Disubstituted Bis‐Tetrahydrofurans from Carbohydrates

Abstract: The diverse bioactivities of annonaceous acetogenins have recently attracted increasing interest. Many of these natural products contain one or more 2,5-disubstituted tetrahydrofuran rings as a core unit; these are important for the bioactivity, since it is believed that these anchor the compounds to the surface of the membrane. Therefore, the synthesis of functionalized bis-tetrahydrofurans is an important task and we have developed a synthetic pathway to all four diastereomeric, partially hydroxylated bis-tetrahydrofurans, that is, 3,6:7,10)-dianhydro-2,8,9-trideoxy-L-erythro-D-ido-undecitol (1), 3,6:7,10-dianhydro-2,8,9-trideoxy-D-threo-D-ido-undecitol (2), 3,6:7,10-dianhydro-2,8,9-trideoxy-L-threo-D-ido-undecitol (3), and 3,6:7,10-dianhydro-2,8,9-trideoxy-D-erythro-D-ido-undecitol (4) starting from D-glucose. The reaction of the aldose with Meldrum's acid led to the C-glycosidic 3,6-anhydro-1,4-lactone 6, which was converted to the aldehyde building block 2,5-anhydro-3,4,7-tri-O-benzyl-6-deoxy-aldehydo-D-ido-heptose (11). Chain elongation of 11 with the Grignard reagent derived from 1-bromo-3-butene gave the diastereomers 3,6-anhydro-1,4,5-tri-O-benzyl-2,8,9,10,11-pentadeoxy-L-glycero-D-ido-undec-10-enitol (12) and 3,6-anhydro-1,4,5-tri-O-benzyl-2,8,9,10,11-pentadeoxy-D-glycero-D-ido-undec-10-enitol (13). The relative threo configuration of the major product 12 was confirmed by X-ray structure analysis. Epoxidation and subsequent cyclization afforded the cis and trans diastereomers 19 and 20, respectively, in a 1:1 ratio. Subsequent cleavage of the protecting groups and separation of the isomers furnished the target compounds in good overall yields.

Method of producing flavonoid compound

Abstract: PROBLEM TO BE SOLVED: To provide a method of simply producing a flavonoid compound which exhibits an aldose reductase-inhibiting action, an active oxygen-eliminating action, a carcinogenesis promotion-inhibiting action, or an antiinflammatory action, and is pharmacologically useful. SOLUTION: This method for producing the compound represented by the formula (I) [R2 is substituted or non-substituted phenyl; R7 is H or OH; (n) is an integer of 1 to 4], is characterized by selectively binding a sugar derivative to a catechin compound through an O-glycoside, and then oxidizing the 4-position of the flavonoid skeleton. COPYRIGHT: (C)2001,JPO

Stereospecific Molybdic Acid-Catalyzed Isomerization of 2-Hexuloses to Branched-Chain Aldoses.

Abstract: On treatment with a catalytic amount of molybdic acid in aqueous solution, the 2-ketohexoses d -fructose, l -sorbose and d -tagatose undergo a stereospecific intramolecular rearrangement to give the corresponding 2-C-(hydroxymethyl)aldoses, 2-C-(hydroxymethyl)- d- ribose ( d -hamamelose), 2-C-(hydroxymethyl)- l -lyxose, and 2-C-(hydroxymethyl)- d -xylose, respectively. At equilibrium, the ratio of 2-ketose to 2-C-(hydroxymethyl)aldose ranged from 14:1 (fructose) to 32:1 (sorbose). A similar treatment of d -psicose failed to yield a significant amount of the corresponding branched-chain aldose. The equilibria can be shifted with the addition of boric acid to the reaction mixture; under these conditions, ratios of 3:1 and 7:1 were obserwed for d -fructose and l -sorbose, respectively. A mechanistic study with d -(3-13C)fructose afforded d -(1-13C)hamamelose, thus confirming C-3C-4 bond cleavage with concomitant C-2C-3 transposition suggested from recent studies with d -(2-13C)fructose.