Expedient Synthesis of Anacardic Acid and Analogues by Suzuki–Miyaura Cross [C(sp2)‐C(sp3)] Coupling and Their Antidiabetic Action

Abstract Anacardic acid and analogues are naturally occurring compounds from the cashew nut ( Anacardium occidentale ) shell liquid (CNSL). Due to its versatile nature, a large number of derivatives have been synthesized and screened for infectious and non‐infectious diseases. Considering the importance of anacardic acid and its derivatives, we present here a facile synthesis of anacardic acid via Suzuki–Miyaura cross‐coupling [C(sp2)‐C(sp3)] from 5‐halo‐2‐methoxy benzoic acid with a BBN complex of a pentadecenyl substrate. The reported strategy has many advantages, such as i) short synthesis, ii) reaction conditions are mild, iii) no hydrogenation step is required, iv) avoids pyrophoric reagents, and v) the reaction is scalable at the multigram level. Further, to prove its synthetic utility, it has been extended to synthesize cardol and cardanol, two other phytoconstituents from A. occidentale , under a protection–deprotection‐free strategy. All the synthesized compounds were studied using in vitro and in‐silico models for α‐glucosidase and lipase inhibitory activity, which are important in antidiabetic action, and found that anacardic inhibits both the enzymes in µM level (3 µM for α‐glucosidase and 30 µM for lipase). Further, their molecular interactions are established through computational biology methods and identified effective interactions with key amino acid residues (α‐glucosidase with Phe450, Trp406, and Arg334; lipase with Ser152, Phe77, and Phe215).