Total Synthesis Of Indole Alkaloid Minfiensine

In 1989.Massiot and coworkers isolated minfiensine from the African plant Strychnos minfiensis and confirmed its structure by using NMR spectroscopy.Its biosynthetic pathway is still not clear,although the indole alkaloid minfiensine is isolated nearly thirty years ago.It also has drawn a great of interest from synthetic chemist since minfiensine exhibited significant biological activities,such as anticancer activities,and contained a highly congested pentacyclic ring system.In the view of retrosynthesis analysis,minfiensine was disassembled into three fragments,namely indole,halogenated amide and butane.The critical problem is ex.ploring the chemical method to content the three f'ragments together.In 2016.our coworkers reported a[3+2]formal cycloaddition reaction.Relying on this strategy,a synthetic route to Strychnos alkaloid(±)-minfiensine was proposed employing an[3+2]formal cycloaddition reaction.Our total synthesis of minfiensine started with phenylhydrazine.Phenylhydrazine uwas subjected to Fisher indole synthesis conditions to afford indole fragment.After removal of indole N-H with NaH,the resulting indole anion was protected with 4-Methoxybenzylchloride at room temperature.Subsequently.we constructed the core structure of tetrahydroiminoethanocarbazole skeleton using an[3 + 2]formal cycloaddition reaction.Then,we used Zn-Cu and catalytic amount of RuCl3 to remove two chlorine atoms and methoxy group,which was then followed by reducing the carbonyl with LiAlH4 to generate the advanced intermediate.Finally,an alkylation reaction,a Heck cyclization reaction and a stille cross-coupling reaction sequentially took place to complete the synthesis of minfiensine.Meanwhile.I also tried to construct the(+)-minfiensine,but without success.In summary,we have achieved the total synthesis of(±)-minfiensine in ten steps from inexpensive starting material and with the high overall yield.