A versatile approach to beta-amyloid fibril-binding compounds exploiting the Shirakawa/Hayashi protocol for trans-alkene synthesis.

Application of the Sonogashira coupling reaction followed by a trans-selective alkyne reduction proved highly adaptable for the efficient synthesis of a class of beta-amyloid fibril binding compounds possessing a styrylbenzene motif such as FSB, an FSB dimer, and (19)F-BAY94-9172.

An expedient synthesis of the fibril binding compound FSB via sequential Pd-catalyzed coupling reactions.

The styryl benzene derivative (E, E)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB), well-known for its binding to beta-amyloid peptide fibrils, was synthesized in an efficient manner exploiting two sequential palladium(0)-catalyzed coupling reactions in a 34% overall yield. This is a substantial improvement to the previously reported synthesis of FSB in 1.1%.