The synthesis of 1 commenced with commercial benzyl alcohol 3 onto which was appended the first guanidine unit on multi-decagram scale under conventional Mitsunobu conditions to furnish ). 9 Eventually it was discovered that when the in situ derived magnesiated guanidine was formed it could direct addition to the desired face furnishing 6 (structure confirmed via X-ray crystallography) as a single diastereomer in 74% yield (decagram scale). Following a-iodination 10 of the remaining enone a convergent coupling with the stannane 18 (see SI) was accomplished via Stille coupling. Of note, Stille coupling proved to be the only viable cross-coupling for this pivotal C-C bond forming step and the initial hit (trace product) was optimized to 70% yield on decagram scale through judicious choice of Pd and Cu sources and ligand. 11 Aldol annulation of adduct 8 using aq. NaOH followed by addition of BnBr led to the hydroxylated tetracycle 9 (structure confirmed via X-ray crystallography) as a single diastereomer. Presumably following aldol addition/dehydration the resulting quinone methide species is immediately captured by hydroxide. It was anticipated that either a simple SN2 reaction of the benzylic alcohol or in situ trapping of the putative quinone methide with an amine source would easily deliver the requisite amine stereochemistry at C-7. In the former case, this proved to be impossible as the benzyl alcohol could not be converted to a leaving group of any kind. For the latter case, only attack by hydroxide was observed rather than any N-based nucleophile employed and addition only occurred from the top face due to a rigid conformation blocking attack from the bottom. A rapid detour was therefore undertaken wherein SN1 substitution using NbCl5/TMSN3 afforded azide 10 (structure confirmed via X-ray crystallography) in 78% yield (single diastereomer) followed by Staudinger reduction (88% yield, gram-scale), and an unusual C-N epimerization (48% yield) to deliver 12 (structure confirmed via X-ray crystallography). With regards to the azide installation, NbCl5 was singularly successful amongst all Lewis-acids screened. The amine redox-epimerization strategy, classically employed for alcohols, is rare in natural product synthesis. In this instance, TPAP/NMO was the only successful oxidant of those screened. Finally, during this step an unusual and fortuitous skeletal rearrangement took place wherein the free amine underwent acyl-transfer thereby protecting itself and setting up a favorable geometry for the ensuing steps. The tenth step of the synthesis yet again required an unconventional solution to a simple reaction: SNAr. Under a variety of known conditions with various nucleophiles only loss of the Boc groups and decomposition was observed, in some cases trace quantities of product could be detected. Ultimately, the use of an ionic liquid ([BMIM]BF4) 14