Structural Development Studies of Subtype-Selective Ligands for Peroxisome Proliferator-Activated Receptors (PPARs) Based on the 3,4-Disubstituted Phenylpropanoic Acid Scaffold as a Versatile Template

Scheme 1

Chemical structure of our PPAR-selective agonist KCL, and the synthetic route. Reagents and conditions: (a) BnBr, KHCO₃, DMF, rt., (b) MeI, K₂CO₃, DMF, rt. (c) NaBH₄, EtOH, rt. (d) PBr₃, ether, 0^°C, (e) (1) (R)-4-benzyl-3-butyryloxazolidin-2-one, LiHMDS, THF, −40^°C–−10^°C, (2) benzyl 5-bromomethyl-2-methoxybenzoate, THF, −40^°C–−10^°C, (f) H₂, 10% Pd–C, AcOEt, rt., (g) (1) ethyl chloroformate, TEA, THF, −10^°C, (2) 4-trifluoromethylbenzylamine, THF, −10^°C -rt., (h) LiOH H₂O, H₂O₂, THF–H₂O, 0^°C.