Molecular Design, Synthesis And Biological Activity Of Indole And Pyrrolidine Nitrogenous Heterocyclic Compounds

The nitrogenous heterocyclic compounds are prevalent in many natural products and artificial pharmaceuticals. Moreover, these molecules have extremely widespread application in medicine, pesticide, dye and other fields. Therefore, more and more organic chemists have dedicated to such research field. In this paper, with the purpose of constructing new types of bioactive nitrogenous heterocyclic skeletons, we carried out a series of research work to design and synthesize a series of new indole and pyrrolidine nitrogenous heterocyclic compounds and made biological activity screening, which are briefly described as follows.Firstly, a highly efficient method for the diversity-oriented synthesis of 32 spiropyrazolone-based tetrahydropyrrole derivatives with potential bioactivities via a facile three-component 1,3-dipolar cycloaddition of aldehyde, amino-ester and unsaturated pyrazolone has been designed and established. And its antitumor activity of the inhibition of human cervical cancer cells—Hela cells was determined by the MTT method. This protocol represents the first 1,3-dipolar cycloadditions of unsaturated pyrazolones with azomethine ylides catalyzed by the easily available HOAc, providing an easy access to spiropyrazolone-based tetrahydropyrroles with structural diversity in high yields(up to 97%) and good diastereoselectivities(up to >95:5 dr), which set a good example to the diversity-oriented synthesis of nitrogenous heterocyclic compounds.Secondly, A chiral phosphoric acid-catalyzed Friedel-Crafts alkylation of o-hydroxybenzyl alcohols with 3-alkylindoles has been established, which was used to construct a biologically important diarylindol-2-ylmethane scaffold in high yields and with good enantioselectivities(up to 99% yield, 90:10 er). Moreover, these novel compounds were subjected to tests to determine the in vitro cytotoxicity against carcinoma Hela cells. Nearly all of the tested compounds exhibited strong or moderate cytotoxicity to Hela cells with IC50 values ranging from 6.821 to 28.042 ug/m L, which might become promising anti-cancer drug candidates after further investigation. This protocol not only provides an efficient method for constructing biologically important diarylindol-2-ylmethane frameworks in an enantioselective form, but also promote the development of o-hydroxybenzyl alcohol-involved catalytic asymmetric transformations.Finally, an organocatalytic Friedel-Crafts alkylation of 2,3-disubstituted indoles with o-hydroxybenzyl alcohols has been established via chemo- and regiospecific C6-functionalization of 2,3-disubstituted indoles, leading to the production of arylindol-6-ylmethane derivatives with potential bioactivities in high yields(up to 99% yield). Moreover, these novel compounds were also subjected to tests to determine the in vitro cytotoxicity against carcinoma Hela cells, and Nearly all of the tested compounds exhibited strong or moderate cytotoxicity to Hela cells with IC50 values ranging from 6.784 to 16.561 ug/m L. This reaction not only represents the first Friedel–Crafts alkylation of 2,3-disubstituted indoles with o-hydroxybenzyl alcohols catalyzed by readily available Bronsted acid Ts OH but also serves as a good example of direct catalytic C6-functionalization of indoles, which have been scarcely investigated.