A general and stereoselective synthesis of the capsaicinoids via the orthoester Claisen rearrangement

Article abstract of DOI:10.1016/0040-4020(96)00414-0

Capsaicin, a main pungent principle of hot pepper, and its 15 analogs have been efficiently synthesized. The key step of this synthetic scheme is the orthoester Claisen rearrangement, which transformed allylic alcohols 2A-C to (E)-alkenoates 3A-C (E/Z > 100) in a highly stereoselective manner. The subsequent carbon chain elongations on 3 based on the cyanation or the malonic acid ester synthesis afforded (E)-alkenoic acids 8, which were converted to the corresponding acid chloride and then coupled with vanillylamine to give capsaicinoids. HPLC and CE (capillary electrophoresis) analyses of these capsaicinoids were also carried out.