Preliminary Studies On Total Synthesis Of Lycopodine

Lycopodium alkaloids are a kind of natural alkaloids with similar structures from the ferns and their related plants?Lycopodiaceae and Huperziaceae?.This plant growth cycle is long,while the alkali content is very low,and because of artificial cultivation research is very limited,that people rely on natural extraction difficult to meet the needs of scientific research.In order to study the biological activity of the alkali,especially in the field of medicine,it is important to explore the efficient synthesis method of the alkaloid.In this paper,we carried out the whole synthesis study on the lycopodine of the lycopene alkaloids,and through the synthesis of the key processes of?-halogenated/halogenated-cyclic enamide?enamidate?with organic boric acid,borate or potassium trifluoroborate to explore the most suitable conditions for its reaction,the results of various factors influencing the reaction yield were obtained,which laid the foundation for the final synthesis of the target molecule,and the other lycopene alkaloid compounds The synthesis provides a useful reference.Through the research of this paper,we have achieved the following results:1.Completed the synthesis of C₅ fragments and C₁₁ fragments in the whole synthesis study,and do the basic research work for the further synthesis.C₅ fragments synthesis,the optimized reaction conditions,the yield greatly improved.Chiral methyl small molecular raw material protected by TBDPS protection,periodic oxidation of chiral compounds 2-15,through Wittig reaction,compound 2-15 and phosphine leaf Lide 2-16 to get C₁₁ chiral fragments.2.Explored the better synthesis method of acid-sensitive functional group trifluoro borate 2-11.3.Investigated the Suzuki-Miyaura coupling reaction of relatively simple compounds2-4 with isobutyl boronic acid,and try to change the conditions such as ligands,bases and solvents to minimize the by-products,thereby increasing the yield of the target product.After the study,we found that the most suitable conditions for the cross-coupling reaction was that Pd?OAc?₂ was used as the catalyst,CPhos was used as the ligand,K₂CO₃ was used as the base,dry toluene was used as the solvent,the temperature was 100?and the reaction time was 24 h.