Study on the Synthesis and Bioactivity of Novel Spiroheterocyclic N-methylisoxazolidine Compuonds Conteining Hydroxyl-lactone
|Keywords||Hydroxy lactone Spiro-heterocyclic compound N-methylisoxazolidine Bioactivity Structure-activity relationship|
Isoxazole derivatives have attracted much attention because of its wide range of biological activities such as anticancer, antitumor, antibacterial, and cell division cycle inhibiting phosphatase enzymes. Research has shown that the introduction of different heterocycles to some molecules can improve the biological activity of the original molecules. In this paper, it is proposed to synthesize a new type of spiro-heterocyclic compounds containing an isoxazole ring. Using D-mannitol as the starting material, and by applying dipolar cyclo-addition, N-methylation, nucleophilic addition and ring closing reactions in order to introduce hydroxy a lactone ring into an isoxazole ring. The purpose is to investigate the reaction mechanisms and to find highly active pharmaceutical precursors. By modifying an isoxazole ring structure one can change the spatial structure of fused heterocyclic molecules into a new structure, broad-spectrum activity of the precursor compound. Nevertheless, from a pharmacological or synthetic standpoint, spiro-heterocyclic compounds are considered to have much more research value, and will provide theoretical evidence for the basic and applied studies of medicine in this new field.This paper is divided into the following two parts:The first part is about literature review, this paper focuses on the progress of isoxazole and salts synthesis; brief introduction of oxazolidine compounds.The second part is about experimental content, the main work is divided into three parts:1. Isoxazoline and trimethyl pyrylium tetrafluoroborate(trimethyl-oxoniumte-trafluorob orate) reaction,N-CH3, get new2-methyl-3-(1’,2’-two-O-ethyl hexyl two oxygen)-5-aryl radicals-3a,6a-two H4,6-two hydrogen oxygen generation azoles and [3’,4’-d] isoxazole tetrafluoroborate derivatives.2. Isoxazole tetrafluorob orate and ethyl acetate in the low temperature reaction, get new2-methyl-3-[(ethoxy carbonyl)methyl]-3-(1’,2’-two-O-ethyl hexyl two oxygen)-5-aryl radicals-3a,6a-two H-4,6-two oxygen generation azoles and [3’,4’-d] isoxazole derivatives.3. Different oxazolidine by1.4M HCl (deprotection), obtained a series of newl-methyl-9-methyl-11-aryl radicals-2a,10a-two-10,12-two hydrogen oxygen generation of azoles and [3’,4’-c]-1,11-benzodiazepines-2,8-two oxygen-5-spiro[4,4]-twelve-7-ketone isoxazole derivatives.