Palladium-catalyzed hydrosilylation of ynones to access siliconstereogenic silylenones by stereospecific aromatic interactionassisted Si–H activation

Hydrosilylation is one of the most important reactions in synthetic chemistry and ranks as a fundamental method to access organosilicon compounds in industrial and academic processes.However,the enantioselective construction of chiral-at-silicon compounds via catalytic asymmetric hydrosilylation remained limited and difficult.Here we report a highly enantioselective hydrosilylation of ynones,a type of carbonyl-activated alkynes,using a palladium catalyst with a chiral binaphthyl phosphoramidite ligand.The stereospecific hydrosilylation of ynones affords a series of silicon-stereogenic silylenones with up to 94%yield,>20:1 regioselectivity and 98:2 enantioselectivity.The density functional theory(DFT)calculations were conducted to elucidate the reaction mechanism and origin of high degree of stereoselectivity,in which the powerful potential of aromatic interaction in this reaction is highlighted by the multiple C–H-πinteraction and aromatic cavity-oriented enantioselectivitydetermining step during desymmetric functionalization of Si–H bond.

Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer

Objective:"Same treatment for different diseases"is a unique treatment strategy in traditional Chinese medicine.Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease(COPD)and lung cancer.Citrus Grandis Exocarpium(Huajuhong in Chinese,HJH),a famous herbal,is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on"syndrome differentiation and treatment"theory.However,the common mechanism for HJH’s treatment of COPD and lung cancer is not clear.Methods:In this study,based on network pharmacology and molecular docking technology,the common mechanism of HJH in the treatment of COPD and lung cancer was studied.The active ingredients and related targets of HJH were integrated from TCMSP,BATMAN-TAM,STP,and Pubchem databases.The standard names of these targets were united by Uni Prot database.Targets of COPD and lung cancer were enriched through Gene Cards,NCBI(Gene),Therapeutic Target Database,and Dis Ge NET(v7.0)databases.Then the intersection targets of HJH and diseases were obtained.The STRING network and the Cytoscape 3.7.2 were used to construct PPI network,the DAVID database was used to perform GO and KEGG analysis.Then Cytoscape 3.6.1 was used to build"ingredient-target-signal pathway"network.Finally,Auto Dock 1.5.6 software was used to perform molecular docking of key proteins and molecules.Results:Eleven active ingredients in HJH were obtained by searching the database,corresponding to 184 HJH-COPD-lung cancer targets intersection.The results of biological network analysis showed that naringenin,the active component in HJH,could mainly act on target proteins such as AKT1,EGFR.Then through positive regulation of vasoconstriction and other biological processes,naringenin could regulate estrogen signaling pathway,VEGF signaling pathway,HIF-1 signaling pathway,Erb B signaling pathway,PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer.Conclusion:Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer.And then,the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described.Furthermore,naringenin was proved to strongly bind with AKT1 and EGFR.It may provide the scientific basis for understanding the"Same treatment for different diseases"strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD,lung cancer and other malignant lung diseases.