Csaba Csutorás

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.

A new and efficient one-pot synthesis of apomorphine and its ring-A halogenated derivatives

Abstract Rearrangement and O-demethylation of codeine (2) and various 6-demethoxythebaine derivatives 6–11 with morphinane skeletone into apomorphine (3) and its halogenated derivatives 20–24 could be efficiently executed in a one-pot operation, by treatment with methanesulfonic acid/methionine.

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.

Microwave-Promoted Acid-Catalyzed Rearrangement of Morphinans : A High-Yield Synthesis of R(-)-Apomorphine

Abstract The microwave‐promoted acid‐catalyzed rearrangement of morphine (1), codeine (2), and thebaine (3) was investigated. In all cases, a significant improvement in the yields were achieved compared to the traditional techniques. R(‐)‐Apomorphine (4), which is a clinically important dopamine agonist, was synthesized from morphine (1) in 75% yield.

Regioselective O-Demethylation of Aporphines with Methanesulfonic Acid / Methionine: An Efficient One-Pot Transformation of Thebaine to (R)(-)-2-Methoxyapomorphine

Abstract 2-Methoxyapomorphine (4) was obtained by the rearrangement of thebaine (1) with methanesulfonic acid in the presence of methionine, a reagent system suitable for the regioselective O-demethylation of aporphine derivatives.

SYNTHESIS OF NEW 3-SUBSTITUTED APORPHINES

The methanesulfonic acid-induced rearrangement of 7-chloro-6-demethoxythebaine (10) in the presence of water or alcohols resulted in new 3-hydroxy-, or 3-alkoxy-11-hydroxy-10-methoxyaporphines (13, 14, 15, 16). O-Demethylation of the 3-methoxy derivative 14 with the methanesulfonic acid/methionine reagent-combination furnished 3,10,11-trihydroxyaporphine (18).

Effect of variety of grapes on trace element and ochratoxin A contents of Hungarian red wines

The quality of wines depends on the soil, the climatic circumstances, the technology, and the variety of grapes. Since the Egri Bikavér (Bulls blood of Eger) is a cuvee wine, for its production, different 1-year-old red wines (Blauburger, Cabernet sauvignon, Cabernet franc, Kékfrankos, Merlot) are mixed in well-selected ratios. Our investigations were focused on red wines of 2007 vintage produced by the same technology from five different varieties of grapes cultivated in the same agricultural area and on the Bikavér produced in 2006 by the mixing of five different 1-year-old wines as mentioned above. The concentration of trace elements and ochratoxin A were determined by inductively coupled plasma sector field mass spectrometry and high-performance liquid chromatography techniques, respectively. It was established that the variety of grapes produced at the same territory has practically no influence on the trace element concentration of the investigated red wines. In addition, the concentration of ochratoxin A has remained in all cases <0.1 µg L−1, considerably lower than the European regulatory limit of 2 µg L−1.