Development and characterization of a FIA system for selective assay of L-ascorbic acid in food samples.

An amperometric detector and an enzymatic reaction were combined for the measurement of L-ascorbic acid. The enzyme cell (containing immobilized ascorbate oxidase) was connected to a flow injection analyzer (FIA) system with a glassy carbon electrode as an amperometric detector. During optimization and measurements two sample injectors were used, one before and one after the enzyme cell, thus eliminating the background interferences. Subtraction of the signal area given in the presence of enzyme from the one given in the absence of enzyme was applied for measuring analyte concentrations and calibration at 400 mV. Analysis capacity of system is 25 samples/hour. The relative standard deviation (RSD) was below 5% (5 times repeated, 400 µmol/L conc.), linearity up to 400 µmol/L, limit of detection (LOD) 5 µmol/L, fitting of calibration curve in 25-400 µmol/L range was R (2) = 0.99.

Synthesis and neuropharmacological characterization of 2-O-substituted apomorphines.

We have synthesized novel 2-O-substituted apomorphines with both different lengths of lipophilic alkyl chains and alkyl chains carrying free hydroxyl groups. Two bis-apomorphines formed as side products of the reactions with diols were isolated and characterized as well. The neuropharmacological profile of all these new compounds were investigated with respect to their binding affinities and activities to dopamine D(2) and D(1) receptors. The obtained data pointed to the fact that, in the examination of dopaminergic activities of 2-substituted apomorphines, the lipophilicity of the substituent is more important than its spatial parameters.

Synthesis of 2-fluoro-11-hydroxy-N-propylnoraporphine: a potential dopamine D2 agonist.

[structure: see text]. 2-Fluoro-11-hydroxy-N-propylnoraporphine 4 (2-F-11-OH-NPa) was synthesized from thebaine in 13 steps with an overall yield of 1.35%. The key steps included the Pd-catalyzed 3-dehydroxylation of 14-hydroxymorphine, S(N)2 substitution of Ts(-) by F(-), and CH(3)SO(2)OH-promoted rearrangement of the substituted morphinandiene. The dopamine binding affinity of this compound was also investigated on rat brain membranes, and as expected, this compound displayed high affinity and selectivity at the D(2) receptor.

Recent developments in the chemistry of thebaine and its transformation products as pharmacological targets.

The most practical synthetic routes to the preparation of as important pharmaceuticals as oxycodone, naloxone, naltrexone, nalbuphine and buprenorphine have utilized the alkaloid, thebaine, as a starting material. This review intends to focus on chemical transformations of morphinans which resulted in morphinandiene derivatives with well-established and novel pharmacological potencies. These chemical transformations were mainly associated with the formation and substitution of the unique diene structure of the ring C of the morphinan backbone.

Synthesis and dopamine receptor binding of sulfur-containing aporphines.

We investigated acid-catalyzed rearrangement of thebaine 14 and its N-propyl analog 15 with methanesulfonic acid in the presence of the nucleophiles methanethiol and hydrogen sulfide. R(-)-2-methylthioapocodeine 16, R(-)-2-methylthioapomorphine 18, and their N-n-propyl analogs 17, 19 were obtained by rearrangement in the presence of methanethiol. However, with hydrogen sulfide, rearrangement of thebaine 14 and its N-n-propyl analog 15 produced sulfide-linked bis-aporphines 21-24 instead of expected R(-)-2-mercaptoapocodeines 12, 13 and R(-)-2-mercaptoapomorphines 10, 11. R(-)-2-Methylthio-N-n-propylnorapomorphine 19 had higher affinity (Ki = 3.7 nM) at D2 receptors in rat forebrain tissue than other novel 2-substituted sulfur-containing aporphines (Ki > or = 50 nM). Behavioral testing of the novel agents in rat indicated moderate locomotor arousal after systemic injection, and none after intragastric administration, indicating poor oral bioavailability.

An investigation of the N-demethylation of 3-deoxymorphine and the affinity of the alkylation products to mu, delta, and kappa receptors.

The N-demethylation of 3-deoxymorphine (1) was investigated using methyl chloroformate and hydrazine. 3-Deoxynormorphine (2) was obtained in 70% yield, and 3-deoxydihydronormorphine (3) was also obtained as a side product. The mu, delta, and kappa receptor binding affinity of a series of N-substituted 3-deoxynormorphines 6 and 7 and N-substituted 3-deoxydihydronormorphines 8-11 was also determined.

Synthesis and neuropharmacological evaluation of R(-)-N-alkyl-11-hydroxynoraporphines and their esters.

We synthesized several N-substituted-11-hydroxynoraporphines and their esters of varying chain length, evaluated their binding affinity at dopamine (DA) receptor sites in rat caudate-putamen membranes, and quantified their effects on motor activity in normal adult male rats. The 11-hydroxyaporphines showed similar neuropharmacological properties to the corresponding 10,11-catecholaporphines. At moderate doses, their esters proved to have more prolonged behavioral actions and superior oral bioavailability.