A stereo-controlled synthesis of 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone and its PPAR activities.
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 α,γ dialkyl γ-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 μM for mPPARα, 9 μM for mPPARδ and >100 μM for mPPARγ.
Ko
Jaeyoung
J
Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, Seoul, Republic of Korea.
Hwang
Hoosang
H
Chin
Jungwook
J
Hahn
Dongyup
D
Lee
Jaehwan
J
Yang
Inho
I
Shin
Kyoungjin
K
Ham
Jungyeob
J
Kang
Heonjoong
H
D000818:Animals; D002460:Cell Line; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D019308:Palmitic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism*; D047229:Plakortis / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007783:Lactones; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D019308:Palmitic Acid