Study on the Synthesis of Lycorine and Phenanthridine-type Alkaloids

Author:Wang Jun Liang

Supervisor:lin jun


Degree Year:2018





The Amaryllidaceae alkaloids are a large family of natural products present in a number of Amaryllidaceae plant species,and lycorine-type and phenanthridine-type alkaloids are a very important class of the amaryllidaceae alkaloids due to lots of the amaryllidaceae alkaloids bearing structural diversity and exhibiting important biological activities,such as antitumor,AChE inhibitory activities,antivirus,anti-inflammatory,anti-malaria,protection of cardiovascular etc.With the increasing demand for such alkaloids,chemical researchers have developed many methods or strategies for the total synthesis of these alkaloids and their analogues.However,the synthetic methods still have some limitations in the terms of universality and practicability.Therefore,it is of great significance to continuously develop a more efficient and maneuverable synthetic methods to achieve high yield,high selectivity and diversity-oriented synthesis of these two alkaloids.In the first chapter,the progress of the research on the alkaloids of lycorine-type and phenyridine-type was reviewed.In the second chapter,focusing on the synthese of lycorine-type alkaloids,we have developed the Michael/Michael cascade reactions catalyzed by organocatalysis to form C ring.The sequence affordes the highly functionalized double Michael adduct with high diastereoselectivity(20:1 dr),high enantioselectivity 92%ee and up to 88%yield in one step after the substrate design and optimization of reaction conditions,which was successfully applied to the formal synthesis of(-)-?-Lycorane in eight steps and 44.1%overall yield.In the third chapter,we have developed a 2-aminoamide reagent that reversibly reacts with ketones in situ via imine formation to serve as a transient directing group for activation of inert C–H bonds and the activation effect was studied systematically,which demonstrates good substrate scop and high regioselectivity.Particularly,the C(sp~3)-H activation process affordes corresponding products with high selectivity(20:1 dr)and up to 93%yield.Also,arylation of sp~2 C-H gives corresponding products in good to excellent yields.In addition,a series of deuteration experiments and control experiments have been performed to provide insight into the reaction mechanism.To further demonstrate the synthetic utility of this tranformation,phenanthridinone and phenaglydon were successfully synthesized by a one-pot method.Finally,the experimental procedures were described in detail and all the intermediates and products were characterized.