Electrochemically Induced Synthesis of Sulfonylated N-Unsubstituted Enamines from Vinyl Azides and Sulfonyl Hydrazides.

Sulfonylated N-unsubstituted enamines were synthesized through a chain of chemical and electrochemical transformations via sulfonylation of vinyl azides. The disclosing of the N-unsubstituted enamines synthesis was based on a unique property of the azido group, which is its ability to eliminate the N2 molecule. Furthermore, a formal paradox is observed: a double bond reacts and a double bond is retained. Electrosynthesis proceeded in an undivided cell equipped with a graphite anode and a stainless steel cathode; NH4I was used as a supporting electrolyte.

Synthesis and structure of 2,4,6-tri-cyclo-butyl-1,3,5-trioxane.

The synthesis and structure of 2,4,6,-tri-cyclo-butyl-1,3,5-trioxane, C15H24O3 1, is described. It was formed in 39% yield during the work-up of the Swern oxidation of cyclo-butyl-methanol and may serve as a stable precursor of the cyclo-butane carbaldehyde. The mol-ecule of 1 occupies a special position (3.m) located at the center of its 1,3,5-trioxane ring. The latter is in a chair conformation, with the symmetry-independent O and C atoms deviating by 0.651 (4) Šfrom the least-squares plane of the other atoms of the trioxane ring. All three cyclo-butane substituents, which have a butterfly conformation with an angle between the two planes of 25.7 (3)°, are in the cis conformation relative to the 1,3,5-trioxane ring. Inter-molecular C-H⋯O inter-actions between the 1,3,5-trioxane rings consolidate the crystal structure, forming stacks along the c-axis direction. The crystal studied was refined a as a racemic twin.

Sea Urchin Embryo Model As a Reliable in Vivo Phenotypic Screen to Characterize Selective Antimitotic Molecules. Comparative evaluation of Combretapyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles as Tubulin-Binding Agents.

A series of both novel and reported combretastatin analogues, including diarylpyrazoles, -isoxazoles, -1,2,3-triazoles, and -pyrroles, were synthesized via improved protocols to evaluate their antimitotic antitubulin activity using in vivo sea urchin embryo assay and a panel of human cancer cells. A systematic comparative structure-activity relationship studies of these compounds were conducted. Pyrazoles 1i and 1p, isoxazole 3a, and triazole 7b were found to be the most potent antimitotics across all tested compounds causing cleavage alteration of the sea urchin embryo at 1, 0.25, 1, and 0.5 nM, respectively. These agents exhibited comparable cytotoxicity against human cancer cells. Structure-activity relationship studies revealed that compounds substituted with 3,4,5-trimethoxyphenyl ring A and 4-methoxyphenyl ring B displayed the highest activity. 3-Hydroxy group in the ring B was essential for the antiproliferative activity in the diarylisoxazole series, whereas it was not required for potency of diarylpyrazoles. Isoxazoles 3 with 3,4,5-trimethoxy-substituted ring A and 3-hydroxy-4-methoxy-substituted ring B were more active than the respective pyrazoles 1. Of the azoles substituted with the same set of other aryl pharmacophores, diarylpyrazoles 1, 4,5-diarylisoxazoles 3, and 4,5-diaryl-1,2,3-triazoles 7 displayed similar strongest antimitotic antitubulin effect followed by 3,4-diarylisoxazoles 5, 1,5-diaryl-1,2,3-triazoles 8, and pyrroles 10 that showed the lowest activity. Introduction of the amino group into the heterocyclic core decreased the antimitotic antitubulin effect of pyrazoles, triazoles, and to a lesser degree of 4,5-diarylisoxazoles, whereas potency of the respective 3,4-diarylisoxazoles was increased.

Rearrangements of organic peroxides and related processes.

This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O-O-bond cleavage. Detailed information about the Baeyer-Villiger, Criegee, Hock, Kornblum-DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately.

Mechanism of electroreduction of the Henry reaction products. Electrochemically initiated degradation of 1-phenyl-2-nitroethanol.

Electroreduction of the Henry reaction product - i.e. 1-phenyl-2-nitroethanol (PNE) - in 0.1 M Bu(4)NClO(4) solution in MeCN has been investigated by a set of experimental (cyclic voltammetry, chronoamperometry, and controlled potential electrolysis) and theoretical (digital simulation and quantum chemical calculations) methods. The results obtained show that cathodically generated radical anion of PNE undergoes C-C bond cleavage reaction resulting in the formation of the free radical of benzyl alcohol and nitromethane anion. The proton transfer between these species affords nitromethane and benzaldehyde radical anion. Electron transfer from the last to PNE initiates the cyclic process of the PNE degradation.

Synthesis and antiproliferative activity of conformationally restricted 1,2,3-triazole analogues of combretastatins in the sea urchin embryo model and against human cancer cell lines.

A series of 1,5-diaryl- and 4,5-diaryl-1,2,3-triazole derivatives of combretastatin A4 were synthesized and evaluated as antimitotic microtubule destabilizing agents using the sea urchin embryo model. Structure-activity relationship studies identified compounds substituted with 3,4,5-trimethoxyphenyl and 3,4-methylenedioxy-5-methoxyphenyl ring A and 4-methoxyphenyl ring B as potent antiproliferative agents with high cytotoxicity against a panel of human cancer cell lines including multi-drug resistant cells. 4,5-Diaryl-1,2,3-triazoles (C-C geometry) were found to be considerably more active than the respective 1,5-diaryl-1,2,3-triazoles (N-C geometry). Compound 10ad' induced G2/M cell cycle arrest and apoptosis in human T-leukemia Jurkat cells via caspase 2/3/9 activation and downregulation of the antiapoptotic protein XIAP. A mitotic catastrophe has been evaluated as another possible cell death mode.

Electrochemically induced multicomponent assembling of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile: a convenient and efficient way to functionalized spirocyclic [indole-3,4'-pyrano[3,2-c]quinoline] scaffold.

Electrochemically induced catalytic multicomponent transformation of isatins, 4-hydroxyquinolin-2(1H)-one and malononitrile in ethanol in an undivided cell in the presence of sodium bromide as an electrolyte results in the formation of spirooxindoles with fused functionalized indole-3,4'-pyrano[3,2-c]quinoline] scaffold in 75-91% substance yields and 500-600% current yield. The developed efficient electrocatalytic approach to medicinally relevant [indole-3,4'-pyrano[3,2-c]quinoline] scaffold is beneficial from the viewpoint of diversity-oriented large-scale processes and represents a novel example of facile environmentally benign synthetic concept for electrocatalytic multicomponent reactions.