Regiocontrolled syntheses of FAHFAs and LC-MS/MS differentiation of regioisomers

Abstract

An efficient regiospecific total synthesis of several branched fatty acyl hydroxyl-fatty acids (FAHFA) has been achieved from available terminal alkenes and alkynes. The key steps feature a boron trifluoride mediated epoxide ring opening with acetylide carbanions, followed by hydrogenation of the alkyne function. The carboxylic acid of the hydroxylated chains is introduced at the last step of the synthesis to allow the esterification of the branched hydroxyl group by fatty acids beforehand. The chemical syntheses of a “linear” FAHFA and a branched FAHFA analog containing a Z-olefin in the hydroxyl-fatty acid chain are also reported. A LC-MS/MS method has been developed. Several reversed phase columns were compared. Regioisomers were separated.