Novel Synthetic Strategies Of Indole And Isoquinoline Alkaloid Derivatives

Aim:As an important component of alkaloids,indole and isoquinoline alkaloids have attracted much attention in their structural modification and derivative preparation in the field of pharmacochemistry.In this work,two synthetic strategies were designed to prepare the derivatives of indole and isoquinoline alkaloids by structural modification of indole and dihydroisoquinoline,respectively.Methods:1.With regard to the preparation of indole alkaloid derivatives,2-ylideneoxindoles 1 were prepared by N-sulfonylation,oxidation and Knoevenagel condensation of indoles.2-ylideneoxindoles 1 reacted with sulfonium bromides 2 and K₂CO₃ to obtain cyclopropane-fused spiro-pseudoindoxyl derivatives 3.The structure of compounds 3 was identified by ¹H-NMR,¹³C-NMR and HRMS and X-ray single crystal diffraction.2.With regard to the preparation of isoquinoline alkaloid derivatives,we intended to use hydrogenated isoquinoline 4 and isatin-derived MBH carbonates 5 to undergo[3+2]cyclization with the absence of catalysis.As a result of[3+2]cyclization,the isoquinoline alkaloid derivatives 6 were obtained,which combined isoquinoline and oxindole.The structures of the novel compounds were determined by ¹H-NMR,¹³C-NMR,HRMS and X-ray single crystal diffraction.Results:Twenty-five C2-spiropseudoindoxyl derivatives 3 were obtained,and nineteen[3+2]cyclization products 6 were obtained in the synthesis of isoquinoline alkaloid derivatives.None of the novel compounds in this paper had been reported before this work.The structure and relative configuration of them were determined by¹H-NMR,¹³C-NMR,HRMS and X-ray single crystal diffraction.Conclusion:The reaction methodology of new indole and isoquinoline alkaloid derivatives has been developed in this project,which also enriches the kinds of indole and isoquinoline alkaloid derivatives,and provides more choices for the development of new drugs and lead compounds.