The thesis is devoted to the development of approaches for the synthesis of new oxazaheterocycles by establishing a correlation between structure of the amino alcohol derivatives of terminal and condensed epoxides and directions of their heterocyclizations.
On the basis of the reactions of 3,4-epoxysulfolane, preparative methods for the synthesis of new tetrahydrothiophene-1,1-dioxides, annulated with 1,3-oxazoline, 1,3-oxazolidine, 1,3,5-dioxazepane, 1,3,5-oxadiazepane, 1,3-oxazolidine-2-one and morpholinone moieties were developed. The synthetic approach to 2,4,6-trisubstituted morpholines by intramolecular Mitsunobu cyclization and piperazines from the corresponding derivatives of glycidyl ethers was proposed. The novel 1,3-oxazolidin-2-ones, morpholines and 1,3-oxazolidines were synthesized by the heterocyclicization of 2-amino-1-(4-nitrophenyl)ethanol under the action of carbonic, oxalic, acetylenedicarboxylic and chloroacetic acid derivatives, as well as mono- and di-aldehydes. It was shown, that introduction into the structure of the starting amino alcohol of a conformationally restricted norbornene fragment complicates the synthesis of morpholindione derivatives. Reactions of N-substituted 2-aminoethanols with cyclic β- and γ-ketosulfones lead to the synthesis of a two new spirocyclic systems: 1-oxa-7-thia-4-azaspiro[4.5]decane-7,7-dioxide and 1-oxa-8-thia-4-azaspiro[4.5]decane-8,8-dioxide. Unsubstituted aminoethanol and 2-hydroxymethyl pyrrolidine react similarly to the primary amines to give the corresponding enamines instead of the spirocyclization product. A new two-step method for the synthesis of amino alcohols with tetrahydrothiopyran-1,1-dioxide fragment was developed. One-pot method for the synthesis of cage-like analogues of the natural immunostimulant Cytoxazone and antidepressant Toloxatone was developed. Starting from diepoxide dicyclopentadiene and using the strategy of "domino-aminolysis of diepoxides" a preparative multigram scale method for the synthesis of new building blocks with the 2-azabicyclo[3.3.1]nonane (2-ABN) pharmacophore fragment has been developed. The method for the synthesis of deuterium-labeled bicyclic methyleneaziridines (MA-d1), which combines aziridine and 1,3-oxazolidin-2-one moieties in their structure was proposed. The method for the synthesis of methyleneaziridino ureas structurally similar to known anticancer agents was proposed. Preparative methods for the synthesis of a number of newly oxazaheterocyclic compounds have been developed. Some of the compounds under in vivo and in vitro tests have shown biological activity (analgesic, tranquilizing, anti-inflammatory, anticonvulsant, antihypoxic, antimicrobial, anticancer).
