Synthesis Of Three Types Of Enamino Ester Derivatives And Determination Of Their Anti-tumor Activity

Enamine esters/ketones are a major category of easy-available reaction substrates,chemical study towards enamine esters/ketones have recieved estensive attention.Multiple of enamine esters/ketones have been applied to the synthesis of heterocyclic compounds,which have considerable value in chemical conversion.The synthesis of some currently-reported anticancer drugs usually requires conditions such as heavy metal as catalyst or high temperature.So the development of simple synthesis of antitumor drugs without metal catalyst has significant academic value and application value.This ariticle has different enamine esters and quinone compounds/halogenated quinone compounds/halogenated benzene dinitriles as starting materials and react with each other respectively,three series of heterocyclic compounds were achieved finally.Then measure their antitumor activity towards human tumor cell lines,most compounds show potent antitumor activity.The first chapter mainly summarizes the structure characteristics,synthetic methods,reaction types of enamine esters/ketones,and their application in the synthesis of heterocyclic compounds.In the second chapter,with acetic acid as catalyst,acetonitrile as solvent,with piperazine ketone enamine esters la-ld as building blocks,and reacting with quinone compounds 2,a series of novel piperazine ketone substrated quinone compounds 3a-3l were prepared rapidly at moderate yields under room temperature.The method posseses advantages as easy-available starting materials,simple synthetic routine,high yield and simple operation,etc.In the third chapter,piperazine ketone enamine esters la-lb and tetrahalogenated-1,4-benzoquinones 4a-4b were simply refluxed for 24 h,then multi-halogen pyrazino[1,2-a]indole-1,8(2H,5H)-diones 5a-5d can be achieved with good yields of 78-83%.When piperazine enamine esters 1 containing a aromatic ring,with Cs2CO3 as catalyst,only by stirring enamine esters le-lj and halogenated benzene quinones 4a-4b at room temperature for 6 h,multi-halogen pyrazino[1,2-a]indole-1,8(2H,5aH)-diones 5e-5p can be synthesized with excellent yields of 85-92%.In the forth charpter,with nitro enamine esters 6a-6m and halogenated benzene dinitriles 7a-7b as starting materials,reaction temperature ranging from 110 ? to 160?,by grinding starting materials under solvent-free for 6-12 min,26 novel halogenated nitro enamine ester derivatives 8a-8z were obtained.R =(6-chloropyridin-3-yl)methy,benzyl,(2-chlorothiazol-5-yl)methyl,4-cyanobenzyl,4-fluorobenzyl,4-chlorobenzyl,4-methylbenzyl,4-methoxybenzyl,4-nitrobenzyl,3-fluorobenzyl,3,5-difluorobenzyl,4-(trifluoromethyl)benzyl,2,4-difluorobenzyl.After accomplishment of synthesis process of designed three series of compounds,compounds 3c,3i,3k,5e,5m,5n and 8a-8z were selected as representatives to test their antitumor activity.The anthropogenic tumor cell lines in vitro screening research results confirmed that 3c,3i,3k,5e,5m,5n posses potent antitumor activity towards common tumor cell line HCT116,and the synthesized compounds 8a-8z posses potent antitumor activity towards four common tumor cell lines:A549,HT29,SGC7901 and HepG2,especially the activity towards A549 is obviously better than the positive contrast drug cisplatin.