. farinosa L., or “true unicorn”, is a North American herb used in traditional medicine to treat inflammation, indigestion, colic, and women's reproductive health problems.5 The common name of this plant hints at its morphological similarity to “false unicorn”, Chamaelirium luteum (L.) A. Gray, which has an overlapping geographical distribution and has been used interchangeably with A. farinosa in herbal medicines.6 The phytochemistry of C. luteum is characterized by steroidal glycosides with structures closely related to cholesterol.7 Limited early literature suggested that these may also be present in A. farinosa.8 However, we recently discovered, unexpectedly, that the major constituent of A. farinosa is the unusual cheilanthane sesterterpene derivative 1 (Chart 1).9 Our efforts to elucidate the complete phytochemical profile of A. farinosa have now delivered three new analogs of 1 (2–4),10 and two novel tetracyclic sesterterpenes 5 and 6 with previously unreported carbon skeletons. Indeed it was clear that significant rearrangement must occur to deliver 5 from the usual terpene precursors. The structural relationship of these compounds coupled with theoretical calculations provide insight into the biosynthetic control of sesterterpene biogenesis.