Studies On The Construction And Anti-Malarial Activity Of Dibenzodiazepine Derivatives

Malaria is a serious parasitic disease caused by Plasmodium infection.It is widespread in more than 80 countries and regions in the world.It is characterized by rapid transmission,wide prevalence and easy recurrence,which poses a serious threat to human health and social development.Treatment of malaria relies mainly on antimalarial drugs,and artemisinin-based combination therapy(ACT)is currently the preferred treatment for malaria.With the increasing incidence of malaria and the number of deaths year by year,the phenomenon of ACT resistance appears and spreads,leading to the increasingly serious situation of malaria control in the world.In this paper,based on the extensive pharmacological activities of dibenzodiazepines,a new synthesis method was developed,a series of derivatives were synthesized and screened for antimalarial activity in vitro.In addition,a new cross-coupling reaction of allyl alcohol and boric acid was developed.The paper is divided into two parts:1 Study on synthesis of dibenzodiazepine derivatives and antimalarial activities in vitroBenzodiazepines derivatives are an important active skeleton,widely existing in a variety of clinical drugs,with anti-psychotic,anti-inflammatory,anti-tumor and other pharmacological activities.Literature studies have shown that some benzodiazepine derivatives have certain antimalarial activity.In order to further study the antimalarial activity of these compounds,we first established a new synthesis method of dibenzodiazepine derivatives.Compared with classical synthesis methods and previous reports,it has the advantages of simple raw materials,mild reaction conditions and no transition metal catalyst.21 dibenzodiazepine derivatives were synthesized by this method.The results showed that compounds 2-3b,2-3d,2-3f,2-3h,2-31,2-3o and 23t showed antimalarial activity against Plasmodium falciparum 3D7,with IC50 values of 0.629 μM,0.801 μM,0.410 μM,0.507 μM,0.769 μM,0.938 μM and 0.467 μM respectively.These datas showed certain antimalarial effects,providing reference for the development of subsequent antimalarial lead compounds.2 Boron-Catalysed Transition-Metal-Free Arylation and Alkenylation of Allylic Alcohols with Boronic AcidsBased on our long-standing interest in the development of environmentally friendly chemical transformations,we also explored the arylation and alylation of allyl alcohols catalyzed by B(C6F5)3.The functionalization of allyl alcohol is an important method to construct allyl derivatives,which mainly relies on the cross-coupling reaction catalyzed by palladium,rhodium,nickel and other expensive and toxic transition metals.According to our method,the allyl alcohol,boric acid and B(C6F5)3 were added to the reaction bottle in the air environment,and stirred at room temperature to construct the allyl derivatives in one step.The reaction is simple,convenient,green,wide range of substrate application,the highest yield up to 91%.In summary,a series of dibenzodiazepine derivatives were synthesized in this paper.After screening for antimalarial activity in vitro,new molecules with certain antimalarial activity were obtained,which provided material basis for further structural optimization and discovery of antimalarial lead compounds.Two new green chemical reactions have been developed to provide more environmentally friendly and efficient strategies for the synthesis of dibenzodiazepines and allyl derivatives.