Study On The [5+6] Cycloaddition Reaction Of Vinylethylene Carbonates

Azalide compounds are a class of heterocyclic compounds with unique chemical structure.As the dominant drug skeleton structure,they are widely found in active natural products and drug molecular structures,such as anti-inflammatory,anti-fungal,anti-tumor,anti-viral and anti-Parasites etc.At present,most reports on azalide compounds are macrolides,and there are few reports on the synthesis methods of medium-sized azalide compounds.Therefore,there is still a large room for development in the synthesis of medium-sized azalides.The design and development of new efficient and environmentally friendly organic synthesis methods to construct novel and unique structures of azalides is of great significance for the research and development of candidate drugs for lactones.A novel and unique structure with strong drug-likeness is obtained through the[5+6]cycloaddition of vinylethylene carbonates and isatoic anhydrides.The method provides new synthetic ideas and methods for synthesizing such azalide compounds with potential biological activity and medicinal development value.The major research contents are as follows:（1）Design the[5+6]cycloaddition reaction of vinylethylene carbonates and isatoic anhydrides as a model reaction.Investigate the influence of factors such as transition metal palladium catalyst,phosphine ligand,reaction time,substrate ratios,loading amount,reaction solvent,reaction temperature and other factors on the efficiency of the[5+6]cycloaddition reaction.Then analyze possible causes and construct an ideal reaction system;（2）Under the optimal reaction system,the general applicability of the reaction was investigated by changing the structure of the reaction substrate.And 41 kinds of novel azalide structures were synthesized with a moderate to excellent yield（18-98%）;（3）The structure of the target products were characterized by ~1H NMR,¹³C NMR,DEPT 135,HSQC,HRMS,IR.The relative three-dimensional configuration of the product is characterized by X-ray monocrystalline diffraction.Moreover,the reaction mechanism of the[5+6]cycloaddition reaction was inferred;（4）The derivatization reactions of azalide compounds were conducted through asymmetric bromine-methoxylation,asymmetric bromine-hydroxylation and catalytic hydrogenation reactions,further confirming the applicability of this research.