Studies toward the synthesis of caramboxin analogues

In 2013, Brazilian researchers isolated the neurotoxin from the star fruit (Averrhoa carambola), the caramboxin (CBX). This toxin has a phenylalanine skeleton, with a stereogenic center in the a-amino acid carbon.The absolute configuration was inferred by comparison of the [a]D values with L-phenylalanine and by theoretical NMR shifts, calculated from DFT. Intrigued by the important and recent discovery of caramboxin, we present the results from our studies toward the synthesis of caramboxin analogs through the ortho-carboxylation of 3,5-dimethoxy benzylderivatives. The three different approaches were tested, and the route involving a Vilsmeier-Haack formylation followed by a Lindgren oxidation provide a potential intermediate for the synthesis of several caramboxin analogs.