Study On Synthesis And Activity Of Tetrasubstituted Alkene Axis Chiral Compounds

As the number of cancer patients increases year by year,the types of cancers are diversified,and chiral anticancer drugs have caused an upsurge of research by scholars.Among chiral compounds,tetra-substituted olefins are important structural units of many drugs and biologically active natural products due to their unique structure and properties,such as the anti-cancer drug tamoxifen,and the drug nilaiprost,which acts on the reproductive system.In this context,we designed a framework of a chiral compound containing a tetra-substituted alkene in this study.At the same time,potential pharmacological structural units（seleno-functional groups and sulfone-based functional groups）are introduced into the tetra-substituted alkene axial chiral framework.Previous people have carried out the research on di-substituted and tri-substituted alkene axial chiral compounds,but there is a little researchs on tetra-substituted alkene axial chiral compounds.According to literature research and preliminary accumulation in laboratories,it is feasible to synthesize such compounds.In this paper,we efficiently synthesized a series of achiral tetra-substituted alkene axis chiral products containing seleno and sulfone functional groups.Using Boc-L-proline as a chiral reagent,we have successfully obtained two chiral products of R configuration and S configuration with an enantiomeric excess of up to 99%.This chiral resolution method has excellent yield,mild reaction conditions and can be scaled up to the gram level.In addition,we found that all compounds have certain anti-tumor effects,and compound 4f is the most sensitive to human melanoma,with an IC₅₀ of 2.9μM.Unfortunately,there is no significant difference in anti-tumor activity between R configuration,S configuration and achiral products.In summary,this article provides a method for synthesizing tetra-substituted alkene chiral compounds containing seleno and sulfone groups with high efficiency and high stereoselectivity by using chiral resolution reagents,and discusses the anti-tumor effect of such compounds.