DBU Catalyzed One-pot Four-component Synthesis of Benzo[a]pyrano[2,3-c]- phenazines and Spiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline] Derivatives

Various phenazine scaffolds are reputed for their significant biological activities. The majority of them can be obtained from natural sources. Other phenazine derivatives, especially benzo[a]phenazines, are found to possess immense biological efficacies, including antimicrobial, antifungal, anticancer, antileukemic, antitumor activities, etc. Constant efforts have been made to increase the biological efficacies by using fusing benzo[ a]phenazine skeleton with the other biologically promising heterocycles. Among many others, benzo[a]phenazine annulated with pyran skeleton was found to exhibit a wide range of biological efficacies like antimalarial, anti-plasmodial, anticancer, antiangiogenic, anticancer activities, etc. These observations motivated us to synthesize some benzo[ a]pyrano[2,3-c]phenazine derivatives under greener conditions by following multicomponent reaction strategies. In this study, we report a facile, straightforward, and environmentally benign highyielding one-pot four-component reaction protocol for the preparation of a series of 3-amino-2-cyano-1- aryl/alkyl-1H-benzo[a]pyrano[2,3-c]phenazines from the reactions of 2-hydroxy-1,4-naphthaquinone, ophenylenediamines, malononitrile, and aromatic/aliphatic aldehydes using DBU (1,8-diazabicyclo[5.4.0]undec- 7-ene) as an efficient organocatalyst in aqueous ethanol under refluxed conditions. Moreover, under the same optimized reaction conditions, a number of spiro[benzo[a]pyrano[2,3-c]phenazine-1,3'-indoline] derivatives were also synthesized in good yields from one-pot four-component reactions of 2-hydroxy-1,4-naphthaquinone, o-phenylenediamines, malononitrile, and isatin or substituted isatins.