Synthesis Of Pyrroloindolines Via Oxidative Cyclization Of Tryptamine Derivatives

In many natural alkaloids products,pyrroloindoline serves as the key structure,and different C3a-substitutions always have important impacts on their biological activities,such as antimalarial,antitumor or as the cholinesterase inhibitor and so on.Although there have been a lot of reports about the synthesis of pyrroloindoline compounds,the introduction of peroxy group and alkoxy group at the C3a position was rarely studied.In this paper,the construction of such compounds has been explored and novel synthesis strategies has been developed.The primary results are summarized as below:?1?Inspired by the kynurenine pathway in the organisms,our research focused on the oxidative cyclization reaction of tryptamine derivatives triggered by peroxy radical produced via TBAI/TBHP catalytic system,giving peroxypyrroloindolenine derivatives efficiently.The reaction has good substrate compatibility as well as moderate to good yields?51-80%?,and the preliminary biological evaluation revealed promising antiproliferation effect against Hela cell lines(IC₅₀=22?M).?2?When methanol was used as the solvent,the selectivity of the oxidative cyclization of tryptamine derivatives catalyzed by TBAI/TBHP system has been significantly changed,giving the C3a-methoxypyrroloindoline as the main product.Thus,we developed a method for synthesizing C3a-alkoxy substituted pyrroloindoline compounds,the yields of which were up to 90%,and achieved the synthesis of natural product CPC-1.