Arrival at macrocycle 15 (the end of the "cyclase phase") was a milestone since all requisite core C-C bonds were in place to arrive at 1 and 2. All that remained was installation of five oxygen atoms at C-5, C-7, C-13, C-14, and C-15. The "oxidase-phase" commenced with oxidation of C-14/15 since olefinoxidations are well-known to be compatible with alkynes. Initial attempts using oxidants (i.e., OsO4, m-CPBA, etc.) delivered undesired stereochemical outcome at C-15 in all cases (Fig. ). Therefore, a net six-electron oxidation catalyzed by ruthenium was chosen to arrive at a diketone , with an eventual strategic reduction to set the desired stereochemistry. Stronger oxidants of this type, however, will not tolerate the presence of an alkyne. For this purpose, an internal protection strategy was designed and achieved upon skeletal reorganization by refluxing 15 and XPhosAuNTf2 (0.8 mol %) in CH2Cl2. The newly-formed tricyclic system reorganized all potentially sensitive sites (nitrogen on C-1, C-4 ketone, C-7-C-8 alkyne, and C-10 alcohol) into their inactive states. Subsequent six-electron oxidation under Rucatalysis led to diketone 16 in a 53% isolated yield (gram-scale) thereby minimizing reliance on PGs.