Total Synthesis of trans, trans-Sanguinamide B and Conformational Isomers

The first total synthesis of Sanguinamide B is reported, prepared via an efficient synthetic strategy. The natural product, trans,transSanguinamide B (1), was generated in a thermodynamic ratio with trans,cis-Sanguinamide B (2) and cis,cis-Sanguinamide B (3). Complete conversion of the cis,cis-Sanguinamide B conformer (3) to the natural product (1) and the trans,cis- conformer (2) was achieved by heating to 170 degrees C. Biological evaluation indicated that the Sanguinamide B conformers disrupted the activity of a virulence determinant in P. aeruginosa.