Improved Synthesis of (E)-12-Nitrooctadec-12-enoic acid, a Potent PPARγ Activator. Development of a "Buffer-Free" Enzymatic Method for Hydrolysis of Methyl Esters.

Endogenous nitro-fatty acids, acting as partial agonist of PPAR , are able to lower the insulin and glucose levels without the side effects associated with common anti- diabetic drugs. (E)-12-Nitrooctadec-12-enoic acid, a potent activator of this peroxisome receptor, was synthesized in a very efficient sequence via a Henry-retro-Claisen ring fragmentation, followed by a novel enzymatic cleavage of methyl esters. The latter method was then applied in the last step of the synthesis of a few labile natural products, such as prostaglandins, isoprostanes, and phytoprostanes.