Because of their widespread distribution in natural products and synthesized compounds with potential bioactivities, spiroheterocycles are regarded as a preferred framework. Among them are C3-spirooxindoles, which have a flexible biological profile produced by several natural and synthetic analogues derived from the combination of C-3 indolyl scaffolds with numerous heterocycles providing various patterns such as horsfiline, elacomine, isoelacomine, rhynchophylline, spirotryprostatin B, and trigolute D [1], [2] (Fig. 1). C3-Spirooxindoles have wide pharmaceutical implementations as anticancer, anti-inflammatory, antimicrobial, antiviral, antidiabetic, and antimalarial agents [3] (Fig. 2).

Spirooxindole chemical synthesis is a fast-emerging research topic in which large-scale studies are being conducted on techniques for green, sustainable, catalytic, and asymmetric synthesis. As starting materials for spirooxindole synthesis, isatin derivatives coupled with amines, active methylene compounds/α,β-unsaturated molecules are often used. MCRs are one-pot synthetic processes in which more than two reactants mix sequentially to produce highly selective products that retain the bulk of the starting material's atoms. MCRs are a key technique in the development of novel drugs. MCRs are frequently expanded into combinatorial, solid-phase, or flow syntheses for the development of novel lead structures of active drugs. Clearly, MCRs are desirable and usable among the many synthetic techniques [1]. Over the last decade, several review publications have reported on the synthesis techniques and biological features of spirooxindoles [2], [3], [4], [5], [6], [7]. Given the biological importance and synthetic hurdles of spirooxindole creation, there is an urgent need to gather recent discoveries in the field. This scientific review summarizes the newly discovered approaches for accessing distinct C3-spirooxindoles categorized according to their medicinal features and uses throughout the previous six years (2018–2023).