Structural Assignment of Daucane Sesquiterpenoids by Low-Effort Total Synthesis and X-ray Crystallography

Total synthesis is an indispensable tool for structural elucidation and thus a cornerstone of natural product research. Lasidiol esters are daucane sesquiterpenoids that have been isolated from various plant genera, particularly from the families Asteraceae and Apiaceae. The structure of lasidiol and one of its esters, lasidiol angelate, was assigned in 1981 by chemical correlation with carotol from Daucus carota. The structural assignment of three other natural lasidiol esters is based on spectral data comparison with lasidiol angelate. In this publication, we validate the previously reported structural characterization of three natural lasidiol esters through a combination of total synthesis and X-ray crystallography. The molecular structures of lasidiol and lasidiol angelate were determined by X-ray crystallography. During the process of structural validation, we were compelled to correct the previously proposed structure of a lasidiol ester derived from Ambrosia trifida. To enable a plant-independent supply of lasidiol and its esters, we devise a seven-step ex-chiral-pool total synthesis to (-)-lasidiol, thereby enabling straightforward access to a wide variety of lasidiol derivatives.