Design,Synthesis And Activity Study Of Novel Sulfur-containing Heterocyclic Nucleoside And Unsaturated Thioalkyl Alcohol Compounds

Cancer has always been a serious threat to people’s health.Malignant tumors have always ranked first in the list of disease mortality rates.Therefore,the research and development of anti-tumor drugs have always been the top priority of drug research and development.Sulfur-containing ring skeleton and sulfanyl skeleton drugs have become the focus of drug research and development due to their own unique physical and chemical properties.This thesis is dedicated to the development of sulfur-containing skeleton compound molecules with good biological activity,and then provides conditions for the discovery of anti-tumor active drugs with independent property rights.Nucleoside drugs are an important class of drugs used clinically to treat tumors and viral infectious diseases.Pharmaceutical chemists can obtain compounds with potential biological activity through various modifications or alterations to the molecular structure of nucleosides.In this paper,the acrylate and unsaturated thiol substituted at the 9 position of the purine base undergo a two-step Michael addition reaction under the catalysis of a base to obtain 22 novel five-membered thioheterocyclic nucleoside compounds,and the reaction is derivatized and released.Lots of experiments.The whole reaction raw materials are easily available,the steps are simple,the reaction conditions are mild,and the yield can reach up to 92%.The structure of the compound was confirmed by hydrogen nuclear magnetic resonance spectroscopy,carbon spectroscopy,high-resolution mass spectrometry and X-single crystal diffraction.The reaction has good universality and can synthesize a variety of five-membered sulfur heterocyclic nucleoside compounds with different substituents.Subsequently,we conducted asymmetric catalytic synthesis of the reaction,but unfortunately the use of chiral catalysts failed to achieve the expected results.D-A ethylene oxide,due to its strong activity,can react with a variety of unsaturated olefins,so it is favored by many researchers.In this dissertation,DA ethylene oxide is used to break the C-O bond under the catalysis of the catalyst silver hexafluorophosphate,and carryed out the Michael addition reaction with unsaturated mercaptans to obtain 24 unsaturated thioalkyl alcohol compounds with potential biological activity in high yields.In addition,studies on amplification and derivatization reactions have been carried out,and excellent yields can still be maintained.In summary,this article uses the reaction of the acrylate substituted at the 9-position of the purine base with an unsaturated thiol to obtain a five-membered thioheterocyclic nucleoside compound;DA ethylene oxide is used to react with an unsaturated thiol to obtain a thioalkyl alcohol compound.The anti-tumor activity of the combined sulfur-containing compounds was studied.The study showed that sulfur heterocyclic compounds showed moderate anti-tumor activity on HCT-116 cells,and the activity research of unsaturated thioalkyl alcohol compounds is in progress.