Total synthesis as a critical tool for structural revision of natural products.

Structural misassignments of natural products remain an important challenge despite significant advances in spectroscopic, chiroptical, and computational methods, owing to factors such as conformational flexibility, limited availability of natural isolates, and stereochemical ambiguity. Total synthesis provides a powerful approach for evaluating and revising proposed structures through direct comparison of spectroscopic, crystallographic, and chiroptical data of synthetic compounds with those of the corresponding natural isolates. This review highlights representative case studies of natural product structural revisions established through total synthesis between 2020 and 2025, including contributions from our laboratory. These examples illustrate the role of total synthesis in resolving structural ambiguities through stereochemical revisions, biosynthesis-guided structural revisions, and complementary computational analyses. Collectively, these studies demonstrate that total synthesis remains an important tool for structural verification and revision, providing a robust foundation for advances in natural product chemistry, biosynthetic studies, and drug discovery.