Study On The Synthesis Of Natural Product Coruscanone A

Coruscanone A is the ethanol extract of the whole Peruvian plant,Piper coruscans H.B.&K.It shows potent activity against Candida albicans and Cryptococcus neoformans,two major opportunistic pathogens associated with AIDS patients.Particular significance is its strong activity against fluconazole-resistant C.albicans strains during fluconazole therapy.lt shows up to a 400-fold less susceptibility to fluconazole.Since its excellent bioactivity,Cormscanone A attracts much interest of pharmacologist and organie chemists.In this dissertation,taking Darzens/ring expansion of monomethyl cyclobutenedione as the key procedure,an altermative method for synthesis of coruscanone A has been developed.The first chapter is about the design background of coruscanone A.Since the Darzens/ring expansion of monomethyl cyclobutenedione is the key procedure in the synthesis of corascanone A,this chapter introduces the Darzens reaction and the reaction of four-membered ring,then the idea for synthesis of coruscanone A is proposed.The second chapter involves the synthetic study of monomethyl cyclobutenedione.Monomethyl cyclobutenedione is an important substrate in preparation of coruscanone A.During the preparation of monomethyl cyclobutenedione,starting materials of dimethyl squarate,diisopropyl squarate and monomethoxy cyclobutenedione,redutants of lithium tri-tert-butoxyaluminum hydride and sodium borohydride were separately tried,and at the same time,the procedures were tried separately or combined.The experimental results show that taking diisopropyl squarate as starting material,methylation,reduction with sodium borohydride and the subsequent rearrangement get the best result.This work presents a simple and high-efficiency strategy for synthesis of monomethyl cyclobutenedione.The last chapter demonstrates the synthetic study of coruscanone A.Starting from monomethyl cyclobutenedione and bromomethyl styryl ketone,eoruscanone B was synthesized through the Darzens/ring expansion key procedure,then the target molecule coruscanone A was furnished by methylation of coruscanone B.This work provides a novel synthetic method for the natural product coruscanone A.