A stereo-controlled synthesis of 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone and its PPAR activities

作者：Ko Jaeyoung; Hwang Hoosang; Chin Jungwook; Hahn Dongyup; Lee Jaehwan; Yang Inho; Shin Kyoungjin; Ham Jungyeob; Kang Heonjoong^*

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(20): 6017-6019.

DOI：10.1016/j.bmcl.2010.08.069

• Nuclear receptor
• PPAR alpha/delta dual agonist
• Marine agonist

A novel class of natural PPAR agonists, 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone (1), were discovered in marine natural product libraries. The synthesis of 1 was accomplished starting from vinylmethyl ketone. Ring formation of the alpha,gamma dialkyl gamma-lactone was achieved via the stereo-controlled reaction of a ketyl radical anion with a chiral methacrylate. In the PPAR agonistic assay, the most potent of the four stereoisomers had EC(50) values of 12 mu M for mPPAR alpha, 9 mu M for mPPAR delta and > 100 mu M for mPPAR gamma.

• 出版日期2010-10-15