Study On The Construction Of Bridged Aza-cyclic Skeleton Of Lyconadin Alkaloids By Heck-type Reaction

Alkaloids,a class of natural products containing nitrogen atoms,are valuable ingredients found in numerous Chinese herbal medicines.As we know,a lot of alkaloids have diverse structure and good biological activity.Notably,many lead compounds with potential medicinal value have been discovered through extensive chemical biology research on the volatile alkaloids.Therefore,it is extremely important to carry out synthetic research on alkaloids to provide material basis for subsequent chemical and biological research.In the synthesis of most alkaloids,how to construct nitrogen heterocycle efficiently is the core problem.Consequently,the development of efficient construction methods of various nitrogen heterocycles can not only facilitate the chemical synthesis of alkaloids,but also promote the development of pharmaceutical chemistry,synthetic chemistry and organic chemistry.Among the many chemical methods for the construction of nitrogen heterocycles,transition metal catalyzed cyclization,as a highly applicable,efficient and regioselective method,has been studied by more and more chemists.This paper mainly introduces the methodology study of the Pd-catalyzed Heck-type reaction developed by our group to construct the core bridged seven-membered-ring systems of lyconadin alkaloids.After studying the structural characteristics of azatricyclic skeleton of lyconadin alkaloids,our group constructed the key tricyclic skeleton of these alkaloids through the Heck-type reaction.At the same time,we realized that this reaction has high novelty and practicability,and developed this reaction into a general method of palladium-catalyzed Heck-type reaction of thiocarbamates tether cyclic enone to construct the corresponding bridged sevenmembered-ring systems,as well as it’s application for the total syntheses of lyconadin alkaloids in a divergent manner.This method is carried out with low catalyst loading,simple operation,wide substrate applicability and high efficiency to prepare the related bridged seven-membered-ring systems.It also can be applied to the total synthesis of natural products to better realize its value and provide an efficient method for the total synthesis of related natural products.