TOTAL SYNTHESIS OF PYRROLE IMIDAZOLE ALKALOIDS ENABLED BY A UNIQUE CHEMOSELECTIVE OXIDATION

Total Synthesis of Pyrrole Imidazole Alkaloids enabled by a Unique Chemoselective Oxidation

The Axinellamines, Massadines, and Palau’amine are complex marine natural products

belonging to the oroidin family isolated from sponge agelas oroides. Their complex structures,

varying modes of functionalities, and biological activities have made them attractive targets for

total synthesis. Although isolated in 1993, Palau’amine was not synthesized until seven years

later due to the incorrect structure being reported. Revision of the structure, as well as the

development of a unique chemoselective oxidation enabled the total synthesis of this natural

product as well as the Axinellamines and Massadines. The approach taken by many groups

towards the total syntheses of these natural products was to build a common core. The direct

oxidation created by Baran and coworkers bridged the gap between building a core and total

synthesis. Baran’s chemoselective oxidation provided a direct route from the guanidine moiety to

the hemiaminal functionality present in these complex structures. Before the syntheses of these

pyrrole imidazole alkaloids, the chemistry of building a core was approached in ways that would

already have a pre-oxidized carbon installed to access the hemiaminal without the use of a direct

oxidation step. Baran’s unique chemoselective oxidation took a direct approach and is the first

for this kind of chemistry. The unique selectivity this oxidation delivered is highlighted by the

installation of the hydroxyl despite the many functionalities present in these complex structures.

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