Csaba Szántay

Role of sodium channel inhibition in neuroprotection: Effect of vinpocetine

Vinpocetine (ethyl apovincaminate) discovered during the late 1960s has successfully been used in the treatment of central nervous system disorders of cerebrovascular origin for decades. The increase in the regional cerebral blood flow in response to vinpocetine administration is well established and strengthened by new diagnostical techniques (transcranial Doppler, near infrared spectroscopy, positron emission tomography). The latest in vitro studies have revealed the effect of the compound on Ca(2+)/calmodulin dependent cyclic guanosine monophosphate-phosphodiesterase 1, voltage-operated Ca(2+) channels, glutamate receptors and voltage dependent Na(+)-channels; the latest being especially relevant to the neuroprotective action of vinpocetine. The good brain penetration profile and heterogenous brain distribution pattern (mainly in the thalamus, basal ganglia and visual cortex) of labelled vinpocetin were demonstrated by positron emission tomography in primates and man. Multicentric, randomized, placebo-controlled clinical studies proved the efficacy of orally administered vinpocetin in patients with organic psychosyndrome. Recently positron emission tomography studies have proved that vinpocetine is able to redistribute regional cerebral blood flow and enhance glucose supply of brain tissue in ischemic post-stroke patients.

Studies aiming at the synthesis of morphine. II. Studies on phenolic coupling of N-norreticuline derivatives

Abstract The synthesis of salutaridine derivatives via phenolic coupling on norreticuline derivatives can be performed in improved yields, using non-metallic oxidizing agents. The assumption of a coordination effect in the preformation of the desired structure is, thus, unnecessary.

A practical route to epibatidine

Abstract A practical synthetic approach to the alkaloid Epibatidine has been developed. This method is convenient and easy to scale up.

Synthesis of vinca alkaloids and related compounds XLVIII synthesis of (+)-catharanthine and (±)-allocatharanthine☆

Abstract The first synthesis of natural (+)-catharanthine (ulbar>1) has been achieved in a few steps and in ∼20 % overall yield based on indole-3--acetic acid. The isomeric (±)-allocatharanthine was also prepared.

Synthesis of vinca alkaloids and related compounds. Part LVI. 15′,20′-Anhydrovinblastine borane complex. Structural investigations using NMR methods.

Abstract In the course of coupling catharanthine 1 to vindoline 2, the 3 borane complex of anhydrovinblastine, a new diindole derivative was isolated. The structure of this compound was studied by detailed NMR investigations. Full1H and13C assignments for both the 3 borane complex and anhydrovinblastine are given.

A PRACTICAL ENANTIOSELECTIVE SYNTHESIS OF EPIBATIDINE

Abstract Two different syntheses of Epibatidine ( 1 ) were designed and carried out using easily accessible reagents and convenient reaction conditions. The ring closure of the prochiral precursor 4 catalyzed by optically active α-phenyl-ethyl-amine gave the key intermediate 5 in over 80% ee from which the natural product (−)- 1 has been prepared.

Chemistry of the wittig reaction, IV Simple conversion of aldehydes to 1,1-dichloroalkane and 1,1-dichloro-1-alkene derivatives, useful intermediates for the synthesis of acetylenic compounds

Abstract The formation of 1,1-dichloroalkanes and 1,1-dichloro-l-alkenes from aldehyde is described using triphenylphosphine - carbon tetrachloride reagent system. Different products can be formed by changing the reaction conditions.

Modifications on the Basic Skeletons of Vinblastine and Vincristine

The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous efforts have been directed towards synthesizing new derivatives of the antitumor agents vinblastine and vincristine so as to obtain novel compounds with improved therapeutic properties.

Convenient synthetic route to (+)-faranal and (+)-13-norfaranal : The trail pheromone of pharaoh's ant and its congener 1

Abstract (+)-Faranal 1a , the trail pheromone of Pharaohs ant, and its congener, (+)-13-norfaranal 1b were synthetized from chiral building block 4 employing diastereoselective carbon-carbon bond formation. The application of crude pig liver esterase enzyme for the preparation of 4 is also discussed.

Absolute configuration and total synthesis of (−)-cabenegrin A-I

Abstract The total synthesis of (−)-cabenegrin A-I [(−)- 1 ] in five steps was achieved from (−)-6a R ,11a R -maackiain [(−)- 5 ], which in turn was prepared by the optical resolution of racemic (±)- 5 using S -(−)- α -methylbenzyl isocyanate as the the chiral auxiliary. The homochirality of (−)-maackiain [(−)- 5 ] and (−)-cabenegrin A-I [(−)- 1 ] was proved by CD measurements. Synthesis of (±)-maackiain [(±)- 5 ] is also presented, starting from the readily available phenol derivatives resorcinol and sesamol, which demonstrates the synthetic utility of the Heck-type oxyarylation process for obtaining pterocarpane derivatives on a multigram scale. A new ring-opening reaction of pterocarpanes (7 → 28) is described.