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 PPARγ, are able to lower the insulin and glucose levels without the side effects associated with common antidiabetic 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.
Department of Organic Chemistry, University of Pavia, Pavia, Italy. gz@unipv.it
Giuseppe
G
Zanoni
Matteo
M
Valli
Lyamin
L
Bendjeddou
Alessio
A
Porta
Paolo
P
Bruno
Giovanni
G
Vidari
D000089:Acetic Anhydrides; D004952:Esters; D005463:Fluoroacetates; D006868:Hydrolysis; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000378:metabolism; D008041:Linoleic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000737:chemistry* / Q000378:metabolism; D014269:Trifluoroacetic Acid / Q000138:chemical synthesis / Q000737:chemistry
C555848:(E)-12-nitrooctadec-12-enoic acid; D000089:Acetic Anhydrides; D004952:Esters; D005463:Fluoroacetates; D007004:Hypoglycemic Agents; D008041:Linoleic Acids; D009574:Nitro Compounds; D047495:PPAR gamma; C017958:trifluoroacetic anhydride; D014269:Trifluoroacetic Acid