N. B. Chernysheva

Reactions of Amidines with 5-Methylene-1,3-dioxolan-2-ones

The composition and yields of the products from the reaction of 4,4-dialkyl-5-methylene-1,3-dioxolan-2-ones with amidines depend on the structure of the initial amidine and on the reaction conditions. 2-Aminopyridines lead to 3-substituted 4-hydroxy-4-methyloxazolidin-2-ones and 4-methylene-oxazolidin-2-ones and also to sym-carbamides. 2-Amino-4,6-dimethylpyrimidine leads to the corresponding 4-methyleneoxazolidin-2-one. 3-Aminothiazoles give linear oxourethanes and sym-carbamides.

Reaction of 4-Methylene-1,3-dioxolan-2-ones with Hydrazines

The structure of the products of the reaction of 4-methylene-1,3-dioxolan-2-ones with hydrazines is a function of the structure of the starting hydrazine. 1,3,4-Oxadiazin-2-one derivatives are obtained from hydrazine hydrate. 3-Arylaminooxazolidin-2-ones are obtained from monoarylhydrazines, while mixtures of these derivatives are obtained from aliphatic monoalkylhydrazines.

Regioselective synthesis of 3,4-diaryl-5-unsubstituted isoxazoles, analogues of natural cytostatic combretastatin A4

4,5-Diarylisoxazoles are potent antiproliferative tubulin-targeting agents. Their isomeric 3,4-diaryl-5-unsubstituted isoxazoles are hardly accessible. The synthesis of 3,4-diaryl-5-unsubstituted isoxazoles 13 was designed based on a condensation of arylbenzaldehydes, arylnitromethanes, and ethoxycarbonylmethylpyridinium bromide followed by a selective one-step transformation of intermediate 3,4-diaryl-5-ethoxycarbonyl-4,5-dihydroisoxazole 2-oxides 8. The orientation of aryl rings in relation to isoxazole heterocycle was confirmed by X-ray crystallography. Targeted compounds were evaluated for antimitotic microtubule destabilizing activity using a phenotypic sea urchin embryo assay. 3-(4-Methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)isoxazole 13e and 13h with a single methoxy substituent were the most potent. Compound 13e showed strong cytotoxicity in NCI60 screen with GI50 for NCI-H522 human lung cancer cell line of 0.023 μM.

The use of 4-(bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as masked α-bromo-α'-hydroxy ketone in the synthesis of heterocyclic systems

Abstract4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one was obtained on the basis of the readily obtainable 4-methylene-5,5-dimethyl-1,3-dioxolan-2-one. It forms 2-imidazo[1,2-a]pyridin-2-yl-2-propanol with 2-aminopyridine, 11a-hydroxy-1,1-dimethyl-3-oxo-1,5,11,11a-tetrahydro[1,3]oxazolo[3,4-a]pyrido[1,2-d]-10-pyrazinium bromide with 2-(aminomethyl)pyridine, and the corresponding derivative of 4-hydroxyoxazolidin-2-one with 2-(3,4-dimethoxyphenyl)ethylamine. The last product was converted by intramolecular amidoalkylation without isolation into 10b-(bromomethyl)-8,9-dimethoxy-1,1-dimethyl-1,5,6,10b-tetrahydro[1,3]oxazolo[3,4-a]isoquinolin-3-one.

Reactions of 5-methylene-1,3-dioxolan-2-ones with amines. Synthesis of 2-oxazolidinones

The reaction of 5-methylene-1,3-dioxolan-2-ones with aromatic or aliphatic amines as well as with the sodium salts of amino acids leads to 4-hydroxy-2-oxazolidinones. The reaction conditions depend on the basicity of the amines. The use of o-phenylenediamine in this reaction leads to the formation of a new heterocyclic system.

Dehydration of 4-hydroxy-4-methyl- 3-phenylamino-oxazolidin-2-ones

The dehydration of two 5,5-disubstituted 4-hydroxy-4-methyl-3-phenylaminooxazolidin-2-ones into the corresponding 4-methylene-3-phenylaminooxazolidin-2-ones has been carried out. The structure of the products was confirmed by X-ray diffraction analysis.

1-oxa-3-azapentalen-2-ones as precursors of cis-2-amino alcohols: Synthesis from propargyl alcohols, CO2, and amines using an intramolecular amidoalkylation reaction of oxazolidin-2-ones

The reaction of 5-methyl-5-(4-methyl-3-pentenyl)-4-methylene-1,3-dioxolan-2-one with primary amines gives the corresponding 4-hydroxy-4-methyloxazolidin-2-ones. These undergo an intramolecular amidoalkylation reaction to form 1-oxa-3-azapentalen-2-ones which are potential precursors of cyclopentanyl cis-2-amino alcohols.