NMR spectroscopic elucidation of the structure and stereochemistry of tricyclic 3-styrylpyrazolines.

Diastereomeric mixtures of tricyclic 3-styrylpyrazolines have been prepared by the reaction of 3-cynnamylidenechroman-4-ones and their 1-thio analogs with hydrazine in hot acetic acid or propionic acid solutions. The diastereomeric mixtures were separated by column chromatography to obtain the pure diastereomers. The elucidation of their structure and stereochemistry and complete (1)H and (13)C assignments have been performed by a combination of various one- and two-dimensional NMR experiments.

Energy-variable collision-induced dissociation study of 1,3,5-trisubstituted 2-pyrazolines by electrospray mass spectrometry.

The pathways of the ([M+H](+)) ions generated from electrosprayed solutions of nine 1,3,5-trisubstituted 2-pyrazoline derivatives were studied using energy-variable collision-induced dissociation (CID) and pseudo-MS(3) (in-source CID combined with MS/MS) methods. It was shown that under CID conditions several structurally important product ions such as the 2,4-substituted azete and 1,2-substituted aziridine ions were formed. The compositions of the product ions were unambiguously supported by accurate mass measurement (mass accuracy was within +/- 8 ppm). The fragmentation pathways of 1,3,5-trisubstituted 2-pyrazolines were established by means of pseudo-MS(3). It was found that a substituent at the N-1 position greatly affects the fragmentation pathways of the 2-pyrazoline derivatives. The 1-acetyl- and 1-propionyl-2-pyrazoline derivatives dissociate mainly through formation of a pyrazolium cation, while in the case of 1-phenyl-2-pyrazoline derivatives product ions arising from the consecutive fragmentation of 2,4-substituted azete and 1,2-substituted aziridine ions dominate. Another interesting finding is the formation of a radical cation from the 2,4-substituted azete by loss of a methyl radical. The fragmentation yield as a function of the collision energy for each of the 1,3,5-trisubstituted 2-pyrazolines was determined. Based on the fragmentation yield versus collision energy curves the relative fragmentation stabilities for the 1,3,5-trisubstituted 2-pyrazoline derivatives were also evaluated.

NMR spectroscopic structure elucidation of the products of the reaction of 3-(3-aryl-3-oxopropenyl)- chromen-4-ones with 1,2-phenylenediamine.

The reaction of 3-(3-aryl-3-oxopropenyl)chromen-4-ones with 1,2-phenylenediamine resulted in the unexpected formation of 10a-aryl-1,2,10,10a-tetrahydrobenzo-[4,5]-imidazo[1,2-a]pyridin-3-yl(2-hydroxyphenyl)-1-methanones. Their structure elucidation and complete 1H and 13C assignments have been performed by a combination of various one- and two-dimensional NMR experiments.

Cinnamylidene ketones as potential modulators of multidrug resistance in mouse lymphoma and human colon cancer cell lines.

The resistance to chemotherapy of cancer cells is mediated by the overexpression of P-glycoprotein, as an ATP-dependent membrane efflux pump. Two families of compounds have been screened, the cinnamylidenecycloalkanones and cinnamylidenebenzocycloalkanones, as promising multidrug resistance (MDR) reversal agents on mouse lymphoma and human colon cancer (COL0320) cell lines. The antiproliferative effects of the cinnamylidene derivatives were tested with the MTT method The MDR effect on drug accumulation was tested by flow cytometry. Combinations of resistance modifiers and cytostatics were tested on the two cell lines to obtain evidence for additive or synergistic interactions. Verapamil was applied as a resistance-modifying positive control. The best effects in the reversal of MDR in both cell lines were exhibited by the methoxy derivatives 2-(2-methaoxycinnamylidene)indan-1-one, 2-(2-methoxycinnamylidene)-3,4-dihydro-2H-naphthalen-1-one, 6-(2-methoxycinnamylidene)-6,7,8,9-tetrahydrocyclohepten-5-one), 2-cinnamylidene-3,4-dihydro-2H-naphthalen-1-one and 6-cinnamylidene-6,7,8,9-tetrahydrobenzocyclohepten-5-one. 2-(2-methoxycinnamylidene) indan-1-one and 2-(2-methoxy-cinnamylidene)-3,4-dihydro-2H-naphthalen-1-one were able to enhance the antiproliferative activity of doxorubicin in a synergistic way.

Enantioselective reduction of C=N double bond by chromium(II) complexes of natural amino acids.

Asymmetric reduction of oximes was performed by chromium(II) complexes of natural amino acids in aqueous phase or in H(2)O/DMF (1:1) solvent. Medium-to-quantitative chemoselectivity (54% to >95%) and low-to-medium enantioselectivity (5-50% ee) were found.

Matrix-assisted laser desorption/ionization and electrospray ionization mass spectrometric study of 2,3-dihydro-1,4-benzoxazepines.

Fragmentations of the protonated adduct ions [M+H](+) of seven 1,4-benzoxazepine derivatives were studied using 'post-source decay' matrix-assisted laser desorption/ionization (PSD MALDI) and electrospray nozzle-skimmer collisionally induced dissociation (ESI-CID) mass spectrometric methods. It was found that both methods generated mainly product ions arising from the cross-ring cleavages of the benzoxazepine ring. Similar product ions were generated under MALDI and ESI conditions; however, it was observed that the loss of the alkylene unit from the N-substituted benzoxazepine, and the loss of a H(2)X molecule (where X = O or S), are more preferred under ESI conditions. Based on the experimental results a mechanism is also proposed for the fragmentation of the oxazepines studied.

Post-source decay matrix-assisted laser desorption/ionization mass spectrometric study of tetracyclic 2,3-dihydro-1,5-benzothiazepines.

The fragmentation behavior of six tetracyclic 2,3-dihydro-1,5-benzothiazepine derivatives cationized with protons and silver ions under post-source decay (PSD) matrix-assisted laser desorption/ionization (MALDI) conditions is reported. The protonated adduct ions decompose into several structurally important fragment ions, including substituted cyclopropane and benzohydrothiazole cations. Elimination of Ag and H and/or AgH from the silver-cationized adduct ions of these ([M+Ag](+)) compounds was observed. It was also found that [M+Ag](+) produced silver-depleted fragment ions exclusively. Based on the PSD results a fragmentation pathway is proposed for the [M+H](+) and [M+Ag](+) precursor ions.

Cationization of simple organic molecules by singly-charged Ag3+ cluster ions in matrix-assisted laser desorption/ionization mass spectrometry: metal cluster-molecule interactions.

It was found earlier that under matrix-assisted laser desorption/ionization (MALDI) conditions several organic compounds which produce adduct with silver ions, are also capable of forming adducts with Ag(3)(+) cluster ions under appropriate conditions. The Ag(3)(+) cluster ion can be in situ generated under the MALDI analysis conditions from silver trifluoroacetate cationization agent in the presence of organic MALDI matrices. In this article the fragmentation of a commercial plasticizer, a peracetylated isoflavone glycoside and a pyrazolylphenyl disulfide derivative cationized with silver ions and Ag(3)(+) cluster ions are compared. It was observed that the complexes of Ag(3)(+) are less fragmented than the corresponding adduct ions with Ag(+). The presumable fragmentation channel of [M + Ag(3)(+)] is the elimination of Ag(2) units from these complexes. No significant dissociation of [M + Ag(3)(+)], into M and Ag(3)(+) takes place, indicating a tight connection between the corresponding molecule and Ag(3)(+) cluster ion. However, with a compound carrying very labile groups, such as the pyrazolylphenyl disulfide derivative, intramolecular cleavages can occur prior to significant dissociation of the Ag(3)(+) cluster ion.

Asymmetric Weitz-Scheffer epoxidation of isoflavones with hydroperoxides mediated by optically active phase-transfer catalysts.

The asymmetric Weitz-Scheffer epoxidation of the isoflavones 3, mediated by the cinchonine- and cinchonidine-derived phase-transfer catalysts (PTCs) 1, affords the enantiomerically enriched isoflavone epoxides 4 with ee values of up to 98% in nearly quantitative yields. With the appropriately configured PTC 1, both enantiomers of the isoflavone epoxides may be obtained by using the commercially available cumyl hydroperoxide 2b as oxidant. Methylation of the hydroxy functionality in the most effective PTC (1b) reduces significantly the enantioselectivity of the isoflavone epoxidation as illustrated for the substrate 3c. This fact indicates the pivotal role of the hydroxy group for enantioselective control, which is rationalized in terms of a hydrogen-bonded aggregate between the ether-oxygen atom of isoflavone 3 and the phase-transfer catalyst 1. The present attractive and convenient method should be useful for the preparation of optically active epoxides of the biologically relevant isoflavone structure.