What Is the True Structure of D609, a Widely Used Lipid Related Enzyme Inhibitor?
What Is the True Structure of D609, a Widely Used Lipid Related Enzyme Inhibitor?
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DOI：
10.1021/acs.orglett.6b00025
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发表时间：
2016-02-19
期刊：
影响因子：
5.2
通讯作者：
Monde, Kenji
中科院分区：
文献类型：
--
作者：
Kato, Mikako;Hammam, Mostafa A. S.;Monde, Kenji
在过去三十年中，D609 (1) 一直被用作脂质相关酶抑制剂。尽管它有八种可能的立体异构体，但尚未对其手性进行系统研究。本文合成了八种可能的手性醇作为 D609 的直接前体，并通过振动圆二色性 (VCD) 技术阐明了它们的立体化学。这些异构体的磷脂酰胆碱特异性磷脂酶 C 和鞘磷脂合酶抑制测定显示它们的活性存在相当大的差异。
D609 (1) has been, used as a lipid-related enzyme inhibitor during the past three decades. Although it has eight possible stereoisomers, no systematic research considering its chirality has been performed,. In this paper, eight possible chiral alcohols as direct precursors of D609 were synthesized, and their stereochemistries were elucidated by a vibrational circular dichroism (VCD) technique. Phosphatidylcholine-specific phospholipase C and sphingomyelin synthase inhibition assays of these isomers showed considerable differences in their activities.