Towards The Total Synthesis Of Marineosin A: Construction Of The Macrocyclic Pyrrole And An Advanced, Functionalized Spiroaminal Model

Herein, we describe the enantioselective construction of the 12-membered macrocyclic pyrrole core of marineosin A in 5.1% overall yield from (S)-propylene oxide. The route features a key Stetter reaction to install a 1,4-diketone, which is subjected to Paal-Knorr pyrrole synthesis and ring-closing metathesis to afford the macrocycle. A divergence point in the synthetic scheme also enabled access to a highly functionalized spiroaminal model system through an acid-mediated hydroxy oxo amide cyclization strategy.