Isotope-Labeling of the Fibril Binding Compound FSB via a Pd-Catalyzed Double Alkoxycarbonylation

We have synthesized two isotopically labeled variants of the beta-amyloid binding compound FSB possessing C-13-labels on the two terminal aryl carboxylic acid moieties. One of these was also fully deuterated on the olefinic spacers. The C-13-isotope labeling was achieved applying a Pd-catalyzed methoxycarbonylation of the corresponding aryl chlorides with externally (ex situ) generated C-13-labeled CO. Application of the Shirakawa-Hayashi protocol for the Pd-catalyzed reduction of a dialkyne intermediate using D2O allowed for the selective deuterium labeling of the two trans-C,C double bonds of FSB.