Synthesis Of 3-hydroxypropanol Oxidized Indole Compounds And Their Anti-tumor Activity Evalution

Through the study,the scientists discovered that the 3-hydroxy quaternary phosphonium oxide skeleton is widely found in many important natural product alkaloids and drug intermediates,and has good biological activity.Therefore,it is an important link in the research and development of 3-hydroxy-quarterly ca rbon-oxide indole skeleton in pharmaceutical and chemincal fields.The literature shows that the nucleophilic addition reaction of indirubin derivatives if obtai ned by using metal as catalyst or using metal reagent as raw material.In this paper,3-chloromethyl oxide indole substrates were used as solvent and glycerol was reacted with glycerol without catalyst under heating.An efficient and gree n nonmetallic catalytic reaction method was obtained,and the yield of the met hod was higher with methanol,ethanol and ethylene glycol.In addition,Severa l synthesized 3-hydroxy quaternary phosphonium oxide compounds were screene d and their antitumor activity was studied to obtain a compound with better ac tivity.The specific tasks are as follows:(1)Synthesis of 3-hydroxypropylene triol oxide.Using 3-chloro-oxide as a substrate against glycerin should be,we carried out the temperature,catalyst,re action solvent and other conditions screening,and finally determine the reaction of the best reaction conditions for the absence of catalyst,glycerol itself as a reaction solvent,at 80 °C reaction.By changing the substituents on the 1,3,5,and 6 positions of the substrate,a total of 26 compounds were synthesized.All compounds were confirmed by 13 C NMR,1H NMR and MS-ESI structures an d the melting points were determined.One of the compounds was single crystal diffracted to give the crystal configuration.(2)Synthesis of 3-alkoxy oxide.Using this new method,we use 3-chl oromethyl indole as substrate,respectively.The product was prouced by reactio n with methanol and ethanol.21 compounds were synthesized in reaction with alcohols.All compounds were confirmed by 13 C NMR,1H NMR and MS-ESI structures and the melting points were determined.One of the compounds was single crystal diffracted to give the crystal configuration.(3)Evaluation of Antitumor Activity.The antitumor activity of 5 compou nds was studied by MTT method.The inhibitory effect of cisplatin on K562 c ells of chronic myeloid leukemia was studied.The experimental results show t hat one compound has better activity and its IC50 value is 52.835 ?mol/L.