Lepadiformine: A case study of the value of total synthesis in natural product structure elucidation

Since the emergence of routine X-ray crystallography and high-field FT NMR in the mid-twentieth century, the importance of total synthesis in structure elucidation has become underappreciated by most organic chemists. However, the limitations and fallibility of spectral methodology has recently been highlighted by the mischaracterization of a number of complex natural products, the correct structures of which were all ultimately assigned by total synthesis. This Account describes how total synthesis was not only instrumental in disproving the erroneously assigned structure of the marine alkaloid, lepadiformine, but also was also pivotal in establishing the correct structure and absolute configuration.