András Földesi

Synthesis and stereochemistry of substituted bi- and tri-cyclic 4,5-dihydropyrazoles

A series of bi- and tricyclic 4,5-dihydropyrazoles have been studied by 1H n.m.r. and 13C n.m.r. spectroscopy and X-ray crystallography. They were synthesised by treating the corresponding mono-and dibenzylidenecycloalkanones and 2-benzylidene-3,4-dihydronaphthalen-1(2H)-one with semi-carbazide, which gave two diastereoisomers, and thiosemicarbazide, which gave only one. The 1H n.m.r. parameters allowed an unambiguous identification of the diastereoisomers and the configuration of one of the isomeric pairs was confirmed by 13C n.m.r. spectroscopy and X-ray crystallography. The crystallographic analysis shows that the six-membered rings assume an intermediate shape between the chair, half-chair and envelope forms, while the five-membered rings have a perfect envelope conformation with C(5) on the flap.

Fused heterocycles. Part 3. Synthesis and stereochemistry of benzopyrano and benzothiapyrano-[4,3-c]pyrazoles

Several tricyclic benzopyrano[4,3-c]pyrazole derivatives have been studied by 1H and 13C n.m.r. spectroscopy. They were prepared by treating 3-benzylidene-chromanones and -1-thiochromanones with semicarbazide or thiosemicarbazide: reactions which give only the cis 3-H,3a-H stereoisomers.

The in vitro Antimycotic Activity and Acute Toxicity of Third-Generation Bezylidenetetralones and Heteroarylidenetetralones

Objectives: A new series of E-2-arylmethylene-1-tetralones and E-2-heteroarylmethylene-1-tetralones (third generation) were designed as potential antimycotic agents against human pathogenic yeasts. Methods: The new compounds were obtained by aldol condensation of 1-tetralone with the appropriately substituted aldehydes in either acid- or base-catalysed conditions. These compounds were tested for their in vitro antimycotic activity against 24 strains of Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum by a microtitre well technique in a liquid casitone medium, using a double dilution method. The toxicity of the new compounds was determined in vitro in cultured HeLa cells, in HeLa growth medium and in vivo in MFI mice. Results: Nineteen new E-2-benzylidine-1-tetralones were prepared, and 16 of the tested compounds showed superior antimycotic activity when compared to the first-generation E-2-benzylidine-1-tetralones synthesised previously. Twelve of these third-generation compounds were more active against different strains of yeasts than 6 commercial antimycotic agents similarly tested. An in vitro toxicity study and an in vivo acute toxicity study in MFI mice showed that these compounds were severalfold less toxic than most of the commerical antimycotics, with 4 being comparable to or less toxic than the least toxic of the commercial agents (amphotericin B) tested by the same procedures. Conclusions: Twelve members of this new E-2-benzylidine-1-tetralone class of compounds are promising candidates for antimycotic agents worthy of further investigation.

Improved Solvent‐Free Synthesis and Structure Elucidation of (E)‐ and (Z)‐4‐(Arylmethylene)‐3‐isochromanones

A series of new 4-(arylmethylene)-3-isochromanones 1−17 has been prepared by base-catalyzed Knoevenagel condensations. Stereochemical and conformational analyses were performed by 1H and 13C NMR methods, and X-ray crystallography was used to complement the configurational assignment for a representative product. The reaction generally yields the (E) isomer, but the isomeric composition of the products was influenced by the aromatic aldehyde and usually governed by the stability of the products. Several aldehydes exclusively afforded the (Z) isomer, due to intramolecular steric/electronic interactions reflected in the increased stability of the product. The condensation performed with ortho-hydroxyarenecarbaldehydes furnished the unexpected 3-arylcoumarins or 3-arylbenzocoumarins. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)