Li Ang group and collaborators of Shanghai organic Research Institute have made progress in the synthesis of indole alkaloids from echitamine / akuammiline family

Indole alkaloids are a large number of natural products with various structures The echitamine / akuammiline indole alkaloids from Oleaceae have complex and interesting chemical structures, anti-inflammatory, antibacterial and anti-tumor activities, which have attracted the attention of synthetic chemists The discovery of echitamine, one of the representative members of the alkaloids, dates back to 1875, but its total synthesis is still challenging Recently, the researchers of Li Ang group, State Key Laboratory of life organic chemistry, Shanghai Institute of organic chemistry, Chinese Academy of Sciences, and the researchers of Syngenta have realized intensive total synthesis of 7 members of the alkaloid family, including echitamine (angel Chem Int ed 2019, 58, 6053) Through the systematic analysis of the chemical structure and biogenic relationship of these alkaloids, they found that deacetylakummiline, a member of the family, can be used as a common intermediate to synthesize other members with more complex structures See Fig 1 for the internal synthesis relationship between these molecules                              1 The synthesis association between some members of the echitamine / akuammiline alkaloid family (source: angelw Chem Int, Based on 3982), a five ring intermediate was prepared by silver catalyzed inner alkyne cyclization and intramolecular indole alkylation, and the core structure of deacetylakummiline was constructed by carbon oxygen bond cutting and carbon nitrogen bond formation reaction Then deacetylakummiline and akuammiline were synthesized by reaction of aldol condensation and oxidation state adjustment It is worth mentioning that the above-mentioned internal alkyne cyclization is an extension of the terminal alkyne cyclization reaction (j.am.chem.soc 2017, 139, 14893) used by Leon's research group in the synthesis of alkaloids from Photinia bicolor Deacetylakummiline was transformed into the corresponding third-order amine nitrogen oxide, and then went through polonovski Potier reaction and [1,2] - meisenheimer rearrangement reaction, respectively The core structure of echitamine was obtained, and then the full synthesis of n-demethylechitamine and echitamine was realized, showing the power of ancient nitrogen oxide chemistry in the synthesis of complex natural products In addition, based on deacetylakummiline, the total synthesis of rhazicine with tetrahydroquinoline structure and pseudoakummidine with tetrahydrofuran and indoline framework was realized by different series reaction ways The above work provides material basis for target recognition and mechanism research of echitamine / akuammiline alkaloids, and also provides useful clues for the analysis of their biosynthesis pathway This research was supported by the strategic leading science and technology program of Chinese Academy of Sciences (class B), National Science Foundation for Distinguished Young Scholars, Syngenta company, etc.