Study On Synthesis And Activity Of Anti-Tumor Activity Alkaloid Olivacine And Its Derivatives

Carbazole alkaloids are an important class of nitrogen-containing aromatic heterocyclic natural products that have a wide range of sources in nature.As early as1872,carbazole nucleus compounds were isolated from coal tar,and more and more carbazole alkaloids were isolated from plants,fungi,and algae.Carbazole alkaloids contain a variety of skeletal structures and abundant functional groups,and have a wide range of pharmacological activities including anti-tumor,anti-oxidation,anti-bacterial,anti-histamine,and anti-inflammatory.In addition,because these alkaloids have a rigid fused ring structure and exhibit special photoelectric properties,they can be used for photovoltaic materials and dyes.The development of methodological and pharmacological studies on carbazole alkaloids with novel structures and good activity has attracted a great deal of interest from organic chemists and drug chemists.Firstly,the research reports on synthesis methods of pyrido[4,3-b]carbazole at home and abroad were reviewed.Based on this,a new method of total synthesis of pyrido[4,3-b]carbazole alkaloids was established.A series of substrate modules with a indol fragment and a diene structure is used to carry out the series reaction between the molecules.The ring-closing product itself already contains the 4-membered polycyclic backbone of the target alkaloid.Next,the lithium ester of lithium hydride is used to convert the ester of C ring of the ring-opening product to methylol,and at the same time,the carbon-oxygen double bond of D ring is removed,and then the hydroxymethyl group is converted into a methyl by the action of trichlorocyanide and sodium borohydride.A methyl intermediate was obtained.After the methyl intermediate is associated with the literature,Ellipticine can be synthesized in one step.The methyl intermediate is reacted with palladium on carbon in a mesitylene solvent to deprotect the D ring from the PMB and form a pyridine ring to obtain a deprotected intermediate.After the deprotected intermediate is associated with the literature,Olivacine can be synthesized in one step.This provides a new idea for the in-depth study of pyrido[4,3-b]carbazole alkaloids.Second,under the inspiration of the previous series of closed-loop reactions,we suspect that this closed-loop condition may be used to close the eight-membered ring in the eight-membered nitrogen heterocyclic ring structure.On this basis,the new method we developed was to use Pd?OAc?₂ as a catalyst and tert-butyl peroxybenzoate as an oxidant in a solvent of 1,4-dioxane:acetic:acid=3:1.The ring-closing substrate was cyclized by refluxing at 60?.And our reaction substrate can be quickly prepared by various tryptamines and various acid chlorides.