Solvent‐Controlled Enzyme‐Catalyzed Friedel–Crafts Reactions of Indoles and Isatins by Using α‐Chymotrypsin

Abstract

Friedel-Crafts reactions between isatins and indoles catalyzed by a-chymotrypsin from bovine pancreas (BPC) are described. The reaction could be controlled by judicious choice of the solvent. 3-Hydroxy-oxindoles and 3,3bis(indol-3-yl)indolin-2-ones were obtained in aprotic (DCE) and protic solvent( MeOH), respectively;t he reactions pro-ceeded at 30 8Cw ith ab road substrate scope in each case. Severalp harmacologically active products were obtained in protic solvent. This method has the potentialt ob ecome as imple, practical procedure fort he synthesis of 3-hydroxyoxindole and 3,3-bis(indol-3-yl)indolin-2-one derivatives.Scheme1.Natural products that contain the 3-hydroxy-2-oxindole structural unit. Scheme2.Representative examples of pharmacologically active 3,3-bis(indol-3-yl)indolinones.[a] J.

Review on Recent Developments in Biocatalysts for Friedel–Crafts Reactions

“…97 Guan and co-workers used this enzyme to perform F−C reactions between indoles and isatins to make 3-hydroxyoxindole and 3,3-bis(indol-3-yl)indolinones. 98 Both are essential scaffolds in the number of natural and pharmaceutical products and have a wide range of biological activities, such as antiviral, anticancer, antibacterial, and anticonvulsant activity. 99 As demonstrated in Scheme 12, stereospecific 3-hydroxyoxindole (44) and 3,3-bis(indol-3-yl)indolinones) (45) were synthesized in dichloroethane and methanol solvent systems, respectively, with the final products obtained in up to 97% yield.…”

“…99 As demonstrated in Scheme 12, stereospecific 3-hydroxyoxindole (44) and 3,3-bis(indol-3-yl)indolinones) (45) were synthesized in dichloroethane and methanol solvent systems, respectively, with the final products obtained in up to 97% yield. 98…”

“…89 Using a commercially available α-chymotrypsin enzyme, biologically important scaffolds (3-hyroxyindole and 3,3-bis(indol-3-yl)indolinones derivatives) were synthesized in excellent yields, pointing toward its pharmaceutical potential. 98 We think that in the near future other biocatalysts such as squalene-hopene cyclases 143 and variants of tryptophan synthases 144,145 could also be exploited to perform F−C reactions using non-natural substrates. The high level of enantioselectivity (up to 93%) of DNA-based catalysts is also very promising if the processes can be scaled up.…”

Chemistry of trisindolines: natural occurrence, synthesis and bioactivity

“…Nevertheless, 5-nitroisatin and 1-methylindole were less reactive, producing relatively lower yields. 107 In general biocatalysts require longer reaction time in comparison with other catalysts.…”

Friedel–Crafts Hydroxyalkylation of Indoles with α-Keto Amides using Reusable K3PO4/nBu4NBr Catalytic System in Water

“…For instance, monoaddition of indole to aldehyde was reported using stoichiometric TMSOTf/ i -Pr 2 NEt and Cs 2 CO 3 . Hydroxyalkylation of indole with activated keto group of isatin was explored using β-cyclodextrin catalyst, urea-choline chloride deep eutectic solvent, DABCO-base ionic liquids, bovine pancreas (BPC) enzyme catalyst, chincona-derived squaramide catalyst, etc. Similarly, trifluoromethyl ketone was utilized as electrophile for indole hydroxyalkylation using guanidine, Cs 2 CO 3 , dinuclear zinc, chincodine catalysts, and catalyst- and solvent-free conditions .…”