Synthesis of NF-kappaB activation inhibitors derived from epoxyquinomicin C.
Synthesis of NF-kappaB activation inhibitors derived from epoxyquinomicin C.
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源自环氧喹诺星 C 的 NF-kappaB 激活抑制剂的合成。
DOI：
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发表时间：
2000
影响因子：
2.7
通讯作者：
K. Umezawa
中科院分区：
文献类型：
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作者：
N. Matsumoto;A. Ariga;S. To;H. Nakamura;N. Agata;S. Hirano;J. Inoue;K. Umezawa
为了开发新的NF-κ B抑制剂，我们设计并合成了环氧喹诺霉素C的去羟甲基衍生物DHM 2 EQ及其区域异构体DHM 3EQ。以2，5-二甲氧基苯胺为起始原料，经5步反应合成了这些衍生物。由于DHM 2 EQ比DHM 3EQ活性更高，毒性更低，因此通过X射线晶体学分析确定了其立体化学构型。保护的DHM 2 EQ的每种对映异构体通过手性柱分离并脱保护。DHM 2 EQ抑制人T细胞白血病细胞中TNF-α诱导的NF-κ B活化，还抑制小鼠类风湿模型中胶原诱导的关节炎。
In order to develop new inhibitors of NF-kappaB activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappaB in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice.