A GENERAL AND STEREOSELECTIVE SYNTHESIS OF THE CAPSAICINOIDS VIA THE ORTHOESTER CLAISEN REARRANGEMENT

Capsaicin, a main pungent principle of hot pepper, and its 15 analogs have been efficiently synthesized. The key step of this synthetic shem e is the orthoester Claisen rearrangement, which transformed allylic a lcohols 2A-C to (E)-alkenoates 3A-C (E/Z > 100) in a highly stereosele ctive manner. The subsequent carbon chain elongations on 3 based on th e cyanation or the malonic acid ester synthesis afforded (E)-alkenoic acids 8, which were converted to the corresponding acid chloride and t hen coupled with vanillylamine to give capsaicinoids. HPLC and CE (cap illary electrophoresis) analyses of these capsaicinoids were also carr ied out. (C) 1996 Elsevier Science Ltd