Spirooxindole Alkaloids: Recent Progress in Synthesis using Isatin as a Versatile Building Block in Multicomponent Reactions

Abstract: Spirooxindole scaffolds are unique molecular structures with diverse biological activities. These compounds were originally extracted from plants belonging to the Rubiaceae and Apocynaceae families. The core structure includes an oxindole moiety that acts as both a hydrogen bond donor and acceptor, along with a cycloalkyl group fused at the C-3 position of the indole ring. The spirooxindole framework is commonly found in bioactive natural products and has emerged as a key pharmacophore in modern drug discovery. Over the past decade, researchers have explored spirooxindoles extensively due to their potential as anticancer agents and their ability to interact with various biological targets. The synthesis of these compounds has significantly expanded the chemical space of oxindoles and other heterocycles, attracting strong interest from synthetic and medicinal chemists. This review discusses recent advancements (2014–2024) in the synthesis of spirooxindoles, with a focus on the use of isatin as a key building block in Multi- Component Reactions (MCRs). Noteworthy strategies being explored include 1,3-dipolar cycloadditions and isocyanide-based Multicomponent Reactions (MCRs), alongside isatin-based MCRs, all of which leverage environmentally benign catalytic systems and cutting-edge nanocatalysts. Additionally, these investigations are incorporating advanced techniques such as microwaveassisted synthesis to streamline reaction times, photochemical processes that harness light energy, and flow chemistry for continuous synthesis.