A Review of Approaches Developed for Spiroether Synthesis

Spiroethers, a subset of natural and synthetic spirocycles, possess various biological activities. These motifs are found in natural products and exhibit anticancer, antidepressant, antiviral, antimalarial, and antituberculosis properties. Because of their exceptional structures, spiroethers can serve as important bioactive scaffolds in the pharmaceutical industry to improve bioavailability and stability and in drug discovery. Many of these compounds can also be used in perfumes and flavors owing to their olfactory properties. Given the increasing interest in spiroether-derived compounds in the pharmaceutical industry and the low yields of spiroethers provided by natural sources, which are not economically viable for industrial demand, synthetic approaches have garnered significant attention. In this review, we provide insight into 16 different approaches suggested for the synthesis of spiroethers; these methods are classified in the following five categories: catalytic methods (four methods), cyclization reactions (three methods), nucleophilic/electrophilic additions (two methods), functional group transformation (three methods), and miscellaneous (four methods). Certain advantages including material availability, high yield, simple procedures, low cost, ability to enhance biological properties of the final products, and so on are reported for these approaches.