'Upenamide: trials and tribulations.

The complex macrocycle 'upenamide was isolated in 2000, stimulating significant effort from synthetic chemists to complete its total synthesis and verify its structure. Progress made by several groups is detailed, culminating in the synthesis of both of the proposed structures of this unique natural product, neither of which matched the natural material according to spectroscopic analysis. The evolution of the synthetic route and the development of associated methodologies are described.