Study On The Synthesis Of Four-and Six-membered Alicyclic Pharmaceutical Intermediate

Alicyclic compounds are a class of organic compounds obtained by different arrangement of carbon skeletons in organic chemistry.Some alicyclic rings are used as active sites and participate in complex biological reaction networks,which are widely present in biomolecules.It also plays an important role in food,clinical diagnosis,fine chemicals,polymers and other fields.Importantly,four-membered and six-membered alicyclic compounds are providing novel,effective,low-toxic and non-pathogenic drugs,catalyzing important changes in the cytoplasm,serving as connectors to increase the rigidity of drug molecules and enhance their efficacy,especially in anti-tumor and chronic disease treatment.In general,alicyclic compounds are an important class of organic compounds.They play a variety of roles in different application fields and are widely used,bringing great convenience to human life.Therefore,the synthesis of quaternary and six-membered alicyclic derivatives is of great significance.This thesis mainly studies the synthesis of nitrogen-containing quaternary and six-membered aliphatic bicyclic compounds and cyclobutane and cyclohexane derivatives containing aminoacetylene.（1）Nitrogen-containing quaternary and six-membered aliphatic bicyclic compounds were synthesized by substitution or reductive amination of nitrogen-containing quaternary aliphatic ring derivatives and six-membered aliphatic ring derivatives such as piperidine,piperazine and morpholine.Through the design,research and exploration of its synthesis route.The results showed that the cyclobutanone derivatives were used as the starting material to react with the six-membered ring containing the amino group under the action of Ti（Oi Pr）₄ and Na BH₃CN to obtain the bicyclic compounds.Compared with other routes,the yield of the product is increased to 60～70%.The experimental route is safe,economical and efficient,green and environmentally friendly,and the raw materials are cheap and easy to obtain.（2）Aminoalkynyl cyclobutane and cyclohexane derivatives were synthesized from cyclobutanol and cyclohexanol derivatives with cis-trans configuration by hydroxymethylsulfonylation,azide configuration reversal,amino deprotection,alkylation of 3-but-yn-yl p-toluenesulfonate,amino protection,azide reduction and other reactions.Various nitrogen-containing aliphatic rings are widely used in pharmaceutical chemistry and organic synthesis.The four-membered ring serves as a linker to increase the rigidity of drug molecules and enhance their efficacy.In order to synthesize pharmaceutical intermediates with quaternary and six-membered rings as the parent,this paper selects the derivatives of quaternary and six-membered aliphatic rings as the research object,and synthesizes the required target product pharmaceutical intermediates through a series of reactions.Through the analysis and discussion of the synthesis process,the reaction conditions were optimized,and the product yield was above 80%.The synthesis route has a high yield and the product is relatively stable.By introducing amino and alkynyl groups,the active sites are increased for broader derivatization.The synthesis of its pharmaceutical intermediates provides convenience for subsequent experimental projects.