Design, Synthesis And Characterization Of Novel Heterocycles Containing Quinolines And Piperonyl Skeleton

Quinoline ring is a back-bone of many natural products and pharmacologically significantcompounds displaying a broad range of biological activities. Especially, heterocyclic compoundscontaining one or two heteroatoms fused to a quinoline ring are found in many natural productsas well as in synthetic compounds, which are known to exhibit anticancer and antitumouractivities and have been popular targets of synthesis. In this thesis, we selected ethyl2-(bromomethyl)quinoline-3-carboxylate as a starting compound to synthesize a variety ofpolycyclic quinoline-fused heterocyclic compounds. All the synthesized novel compounds havealready characterized by spectral data and elemental analyses. The thesis was mainly consisted offour parts.In the first part, the property, synthesis and application of quinoline and its derivatives andthe property, synthesis and application of benzo[d][1,3]dioxole are reviewed.In the second part, the hitherto unreported naphtho[2’,1’,6,7]oxepino[3,4-b]quinolin-7(14H)-one (7) and naphtho[1’,2’,6,7]oxepino[3,4-b]quinolin-15(8H)-one (8) weresynthesized by the intramolecular Friedel-Crafts acylation reaction of6-((naphthalen-1-yloxy)methyl)-[1,3]dioxolo[4,5-g]quinoline-7-carboxylic acid (4) and6-((naphthalen-2-yloxy)methyl)-[1,3]dioxolo[4,5-g]quinoline-7-carboxylic acid (6) under thetreatment of Eaton’s reagent (P2O5-MeSO3). Compounds4and6were prepared by a one-potreaction of ethyl6-(chloromethyl)-[1,3]dioxolo[4,5-g] quinoline-7-carboxylate (2) withα-naphthol and β-naphthol, respectively. The resulting target products could be further treatedunder basic conditions to undergo1,2-Witting rearrangement and atmospheric oxidation givingthe corresponding naphthoacridi-nediones (7) and (8).In the third part, a facile and efficient one-pot procedure for the preparation of2-(1-benzofuran-2-yl)quinoline-3-carboxylic acid derivatives is described, featuring threedifferent synthetic transformations, namely Willamson ether synthesis, hydrolysis of an estergroup at the quinoline ring C-3position, and intramoleuclar electrophilic cyclization reactionbetween the aldehyde group of salicylaldehyde or substituted salicylaldehydes and the methyleneat the quinoline ring C-2position. In the forth part, a series of novel2-styryl-3-carboxyquinolines (13a-c) have beensynthesized via three-step one-pot procedure which involved in situ formation of the Ylide (11)from the reaction between the starting compound (2) and triethyl phosphite followed by theWittig-Horner reaction with aromatic or heteroaromatic aldehydes and subsequent basichydrolysis. The resulting (E)-6-styryl-[1,3]dioxolo[4,5-g]quinoline-7-carboxylic acid (13a-c)could be further treated by PPA to give the corresponding12H-benzo[4,5]tropono[1,2-b]quinolines (14a) via intramolecular cyclization reaction.