Enzyme/NaBF₄-catalyzed Synthesis Of Bis（indolyl）alkanes

Bis(indolyl)methane and their derivatives are members of an important class ofheterocyclic compounds that display diverse biological properties. In this paper, three catalytic systems were investigated for the synthesis of bis(indolyl)methanes:(1)Na BF4-catalyzed synthesis of bis(indolyl)alkanes in ethanol aqueous solution;(2)α-chymotrypsin-catalyzed synthesis of bis(indolyl)alkanes in ethanol aqueous solution;(3)protease-catalyzed synthesis of bis(indolyl)alkanes in water. This paper mainly consists of four parts:The first part: Literature review. The review covers the latest results on the synthesis of bis(indolyl)methanes.The second part: Na BF4-catalyzed synthesis of bis(indolyl)alkanes in ethanol aqueous solution. A tandem reaction catalyzed by Na BF4 to synthesize bis(indolyl)methanes starting from indole and aromatic aldehydes in ethanol aqueous solution was reported for the first time, and 12 bis(indolyl)methanes were obtained. The reaction was carefully optimized with different catalysts, mixture solvents, ethanol contents, temperatures and the reaction time, and 10 mol% Na BF4 can works efficiently for the tandem reaction of indole with aromatic aldehydes in 30% ethanol aqueous solution at 60 o C to yield a series of bis(indolyl)alkanes in 72%-97% yield.The third part: α-Chymotrypsin-catalyzed synthesis of bis(indolyl)alkanes in ethanol aqueous solution. In ethanol aqueous solution, α-chymotrypsin showed excellent catalytic activity for the tandem process between indole and aromatic aldehydes, and 12bis(indolyl)methanes were obtained. After investigating enzyme sources, reaction media,temperature, enzyme concentration and the structure of substrate, a wide range of aromatic aldehydes could react with indole in 30% ethanol aqueous solution at 60 o C to afford the desired products with moderate to good yields(from 68% to 95%) using a littleα-chymotrypsin as catalyst.The fourth part: Protease-catalyzed synthesis of bis(indolyl)alkanes in water. A novel methodology for the synthesis of bis(indolyl)methane by the reaction of aromatic aldehyde and indole in water has been developed, and the influences of the reaction media, enzyme sources, temperature, the enzyme concentration and the structure of substrate were investigated. α-Chymotrypsin showed excellent catalytic activity for a series of substrates and lead to the formation of 10 bis(indolyl)alkanes in 65%-97% yields.Three catalytic systems, which are mild, convenient, efficient and eco-friendly routes,have been developed for the synthesis of bis(indolyl)alkane and their derivatives, and it is beneficial for promoting the development of the methodology in organic synthesis.