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

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

doi:10.1016/j.bmcl.2010.08.069

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

Bioorg Med Chem Lett. 2010 Oct 15;20(20):6017-9. doi: 10.1016/j.bmcl.2010.08.069. Epub 2010 Aug 19.

Authors

Jaeyoung Ko¹, Hoosang Hwang, Jungwook Chin, Dongyup Hahn, Jaehwan Lee, Inho Yang, Kyoungjin Shin, Jungyeob Ham, Heonjoong Kang

Affiliation

¹ Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, Seoul, Republic of Korea.

PMID: 20822906
DOI: 10.1016/j.bmcl.2010.08.069

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line
Lactones / chemical synthesis
Lactones / chemistry*
Lactones / pharmacology*
Molecular Structure
PPAR alpha / agonists
PPAR alpha / metabolism
PPAR gamma / agonists
PPAR gamma / metabolism
Palmitic Acid / chemical synthesis
Palmitic Acid / chemistry
Palmitic Acid / pharmacology
Peroxisome Proliferator-Activated Receptors / agonists*
Peroxisome Proliferator-Activated Receptors / metabolism*
Plakortis / chemistry
Stereoisomerism
Structure-Activity Relationship

Substances

Lactones
PPAR alpha
PPAR gamma
Peroxisome Proliferator-Activated Receptors
Palmitic Acid