立体控制合成 2,4-二甲基-4-羟基-16-苯基十六烷酸 1,4-内酯及其 PPAR 活性。
A stereo-controlled synthesis of 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone and its PPAR activities.
机构信息
Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, Seoul, Republic of Korea.
出版信息
Bioorg Med Chem Lett. 2010 Oct 15;20(20):6017-9. doi: 10.1016/j.bmcl.2010.08.069. Epub 2010 Aug 19.
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.
一类新型天然过氧化物酶体增殖物激活受体（PPAR）激动剂，2,4-二甲基-4-羟基-16-苯基十六烷酸 1,4-内酯（1），从海洋天然产物库中被发现。1 的合成从乙烯基甲基酮开始。α，γ-二烷基γ-内酯的环形成是通过酮基自由基阴离子与手性甲基丙烯酸盐的立体控制反应来实现的。在 PPAR 激动剂测定中，四种立体异构体中最有效的一种对 mPPARα 的 EC50 值为 12 μM，对 mPPARδ 的 EC50 值为 9 μM，对 mPPARγ 的 EC50 值大于 100 μM。
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