We noted, however, that the basic aniline moiety of 1-3 would be protonated under acidic conditions, therefore requiring a dicationic species (4) along the epimerisation/isomerisation pathway (Scheme 1). Formation of such a dication generally requires highly forcing conditions, due to the destabilising effect of the two positive charges in close proximity. It therefore seemed plausible that interconversion of the spiroketal core may effectively be prevented by the presence of the basic nitrogen atom, protecting the overall integrity of the spirocentre. Since the goji berry possesses an acidic environment (pH ~ 5.3), an unusual spiroketal acid-stability of 1-3 may be important to enabling distinct roles of each isomer in the biochemistry of L. barbarum. Motivated by these questions, we undertook the total synthesis of the lycibarbarines (1-3) to investigate the properties of their spiroketal core and gain synthetic access to their unique structures for the first time. Scheme 2. Retrosynthetic analysis of lycibarbarines A-C (1-3).