Synthetic approaches to CYN started with the piperidine ring (A), and progressed to annulation of rings B and C. The first total synthesis of CYN was reported in 2000 through a 20-step process.
Improvements to synthetic methods led to a revision of the stereochemistry of CYN in 2001. A synthetic process controlling each of the six stereogenic centres of epiCYN established that the original assignments of both CYN and epiCYN were in fact a reversal of the correct structures. An alternative approach by White and Hansen supported these absolute configurations (Figure 5). At the time of this correct assignment, it was suggested that the enol form was not dominant.