Synthesis of Aloperine-Containing Mannich Bases of Isoflavones

Abstract

The possibility of using the alkaloid aloperine for aminomethylation of a chromone ring was studied. A series of 8- (aloperin-12-yl)methyl-substituted isoflavone derivatives were synthesized.In continuation of research on the ability of quinolizidine alkaloids to undergo electrophilic substitution on a chromone ring of flavonoids [1-3], we studied the alkaloid aloperine (1) isolated as a minor constituent from seeds and leaves of Sophora alopecuroides L. [4][5][6][7][8] or synthesized by the published methods [9][10][11][12].Aloperine exhibits anti-inflammatory and antiallergic activity [13], which is responsible for its therapeutic effect in treating allergic contact dermatitis and eczema [14]. Furthermore, aloperine is a promising chemotherapy agent with significant antiproliferative activity against HCT116 cancer cells. It initiates apoptosis and halts the cell cycle [15]. It is noteworthy that aloperine also has antiviral activity against influenza A virus (IAV) [16]. The synthesis of aloperine derivatives is just as interesting with respect to chemistry and pharmacology. Thus, the synthesis of N(1)-alkyl aloperine derivatives that improved the potency against H1N1 influenza A virus by five times was reported [16].The intersection of the biosynthetic pathways for alkaloids and flavonoids in a single plant species results in the formation of metabolites containing both fragments. The clearest examples of this are the anticancer alkaloids tonkinensine A and B, which were isolated from Sophora tonkinensis [17].The reaction of aloperine and isoflavone under Mannich reaction conditions was studied in order to synthesize similar compounds containing them. The CH components were natural 7-hydroxyisoflavones 2a-d and their analogs 2e and 2f. An important aspect of our research was to find suitable conditions for carrying out the Mannich reaction because it can occur under both base and acid catalysis. As it turned out, the best results were obtained by carrying out the Mannich reaction using paraformaldehyde in anhydrous EtOH in the presence of catalytic amounts of 4-N,N-dimethylaminopyridine (DMAP).

A Review of the Synthesis and Biological Activity of Flavonoid Mannich Base Derivatives

“…Its potential as a therapeutic agent against AD suggests that it could be further explored and studied for its efficacy and safety in future drug development efforts. [74] According to the findings presented in reference, [75] a synthesis strategy was employed to produce Mannich bases of isoflavones containing Aloperine, leading to the formation of compounds 155 a-f as shown in Scheme 18. Furthermore, the research team conducted an investigation to identify the optimal conditions for the Mannich reaction, considering both basic and acidic catalysis.…”