Synthetic Studies Towards Dactylicapnosine A?Dactyllactone A And Cryptaustoline-like Isoquinolines

The aporphine alkaloids are a diverse family of isoquinoline alkaloids with polycyclic structures and a broad range of biological activities.Recently,two novel aporphine alkaloids,namely Dactylicapnosine A(2-27)and Dactyllactone A(3-1)were isolated from Dactylicapnos scandens.These two aporphine alkaloids are bioactive molecules with a highly oxygenated and rearranged D-ring system,and both skeletons have never been identified in previous reported aporphines.Dactylicapnosine A(2-27)showed biological activities for inhibiting neuralgia,with an IC50value of 1.78±0.23?M.Dactyllactone A(3-1)exhibited anti-inflammatory activity in vitro significantly by inhibiting the expression of IL-1? and PGE2.#1237 aporphine alkaloids nucleus 2-27 Dactylicapnosine A 3-1 Dactyllactone AThe novel skeletons as well as its biological activities of Dactylicapnosine A(227)and Dactyllactone A(3-1)have attracted our synthetic interests.It is of importance to develop a practical synthetic route to provide access to Dactylicapnosine A(2-27),a rare constituent from Dactylicapnos scandens.By the way,both Dactylicapnosine A(227)and Dactyllactone A(3-1)have never been prepared by total synthesis.Through total synthesis,we could provide enough amount of Dactylicapnosine A for further biological studies.In this thesis,we reported the synthetic studies towards these two natural products based on a bio-inspired synthetic approach.This thesis contains five chapters.In chapter 1,the research progress of aporphine alkaloids,including classifications and structure characteristics of the aporphine alkaloids,pharmacological activity and structure-activity relationships of aporphine alkaloids,biosynthetic pathway of aporphine alkaloids and synthetic efforts on aporphine alkaloids are summarized.In chapter 2,we describe our work on the total synthesis of Dactylicapnosine A(2-27).The 1,4-diketone-2-hydroxyl compound 2-201 was obtained and converted to a key intermediate(2-204)for the synthesis of Dactylicapnosine A(2-27)via benzilic acid rearrangement.Based on this bio-inspired benzilic acid rearrangement,the first total synthesis of Dactylicapnosine A(2-27)was completed in 10 steps and 5.2%overall yield.#12We describe our progress in the synthesis of Dactyllactone A(3-1)in chapter 3.We successfully synthesized a key intermediate(2-211)of Dactyllactone A(3-1)by manipulation of 1,4-diketone-2-hydroxyl compound 2-208 based on a benzilic acid rearrangement.Transformation of this key intermediate to Dactyllactone A(3-1)is currently conducted in our laboratory and the results will be reported in the near future.#12In chapter 4,studies on the formation of C-N bond in cryptaustoline type isoquinoline alkaloids were reported.Compound 4-41 and its analogues were used to synthesize 4-42,5,6-dihydro indole[2,1-a]isoquinoline,by CuI catalyzed C-N coupling reactions.#12Chapter 5 records the experimental operations of our research work.We also presented the physical and spectral data of new compounds in chapter five.