Evidence that the multiflorine-derived substituted quinazolidine 55P0251 augments insulin secretion and lowers blood glucose via antagonism at α -adrenoceptors in mice.

Aims: To investigate the mechanism of action of 55P0251, a novel multiflorine-derived substituted quinazolidine that augments insulin release and lowers blood glucose in rodents, but does not act via mechanisms addressed by any antidiabetic agent in clinical use.

Materials And Methods: Using male mice, we determined the effects of 55P0251 on glucose tolerance, insulin secretion from isolated islets and blood oxygen saturation, including head-to-head comparison of 55P0251 to its inverted enantiomer 55P0250, as well as to other anti-hyperglycaemic multiflorine derivatives discovered in our programme.

Results: 55P0251 was clearly superior to its inverted enantiomer in the glucose tolerance test (area under the curve: 11.

Preclinical characterization of 55P0251, a novel compound that amplifies glucose-stimulated insulin secretion and counteracts hyperglycaemia in rodents.

Aims: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action.

Materials And Methods: Pharmacokinetic properties of 55P0251 were portrayed in several species.

55P0110, a Novel Synthetic Compound Developed from a Plant Derived Backbone Structure, Shows Promising Anti-Hyperglycaemic Activity in Mice.

Starting off with a structure derived from the natural compound multiflorine, a derivatisation program aimed at the discovery and initial characterisation of novel compounds with antidiabetic potential. Design and discovery of the structures was guided by oral bioactivities obtained in oral glucose tolerance tests in mice. 55P0110, one among several new compounds with distinct anti-hyperglycaemic activity, was further examined to characterise its pharmacology and mode of action.

Synthesis and characterization of the hexenuronic acid model methyl 4-deoxy-beta-L-threo-hex-4-enopyranosiduronic acid.

A facile synthetic scheme for the preparation of methyl 4-deoxy-beta-L-threo-hex-4-enopyranosiduronic acid utilizing the commercially available methyl alpha-D-galactopyranoside as starting material has been developed. The synthesis sequence comprises six high yielding reaction steps: TEMPO oxidation, acetylation, methanolysis of the lactone, acetylation, beta-elimination, and final removal of the protecting groups. Only one column chromatographic purification is needed throughout the whole sequence.

An optimized CZE method for analysis of mono- and oligomeric aldose mixtures.

An optimized capillary electrophoresis (CZE) method to analyze complex mixtures of aldoses was developed. The approach allows simultaneous quantitative analysis of all four isomeric aldopentoses, eight aldohexoses, as well as xylo- and cellooligosaccharides up to the tetraoses. UV tagging with 4-aminobenzoic acid ethyl ester (ABEE) in combination with reductive amination was used as pre-column derivatization.

Kinetic and chemical studies on the isomerization of monosaccharides in N-methylmorpholine-N-oxide (NMMO) under Lyocell conditions.

The Lyocell process is a modern and environmentally fully compatible industrial fiber-making technology. Cellulosic pulp is dissolved without chemical derivatization in a melt of N-methylmorpholine-N-oxide monohydrate (NMMO). In the present work, the reactions of monosaccharides under Lyocell conditions were investigated in detail, using capillary zone electrophoresis as the analytical technique to clarify the composition of reaction mixtures and to follow the kinetics.

Crystal and molecular structure of methyl 4-O-methyl-beta-D-ribo-hex-3-ulopyranoside.

Methyl 4-O-methyl-beta-D-ribo-hex-3-ulopyranoside (2), a model compound for partially oxidized anhydroglucose units in cellulose, was crystallized from CHCl(3)/n-hexane by vapor diffusion to give colorless plates. Crystal structure determination revealed the monoclinic space group P2(1) with Z = 2C(8)H(14)O(6) and unit cell parameters of a = 8.404(2), b = 4.

Synthesis of oxidized methyl 4-O-methyl-beta-D-glucopyranoside and methyl beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside derivatives as substrates for fluorescence labeling reactions.

The synthetic cellulose model compounds methyl 4-O-methyl-beta-D-glucopyranoside and methyl 4-O-methyl-beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranoside and related 6-O-protected intermediates were oxidized in good to fair yields using Swern-conditions or bromine/bis(tributyltin) oxide, respectively, to afford compounds containing 6-aldehyde, 3-keto, and 2,3-diketo groups. Cellobiose and oxidized monosaccharides were then labeled with the carbonyl-selective fluorescence marker 9-(7-amino-1,4,7-trioxaheptyl)-9H-carbazolecarboxamide (CCOA). The labeled derivatives serve as model compounds for the determination of minute amounts of carbonyl groups in cellulosic polysaccharides.