Synthetic Route to Optically Pure Norcantharidin Analog NCA-01, a Highly Selective Protein Phosphatase 2B inhibitor, and Its Derivatives
Synthetic Route to Optically Pure Norcantharidin Analog NCA-01, a Highly Selective Protein Phosphatase 2B inhibitor, and Its Derivatives
复制标题
高选择性蛋白磷酸酶 2B 抑制剂、光学纯去甲斑蝥素类似物 NCA-01 及其衍生物的合成路线
DOI：
10.1002/asia.201200077
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发表时间：
2012
影响因子：
4.1
通讯作者：
Tadashi Shimizu
中科院分区：
文献类型：
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作者：
Tadashi Shimizu
开发了一种高效的光学纯去甲斑蝥素类似物NCA-01的合成路线，NCA-01是一种高度选择性的蛋白磷酸酶2B（PP 2B;钙调神经磷酸酶）抑制剂。通过X射线晶体学分析确定对映异构体的绝对立体化学。以类似的方式合成在C1位具有各种取代基的光学纯NCA衍生物。NCA-01及其衍生物的PP 2B-抑制活性与对映体形式无关。NCA-01二甲酯有效抑制Jurkat细胞中IL-2的产生。
An efficient synthetic route to optically pure norcantharidin analogue NCA‐01, a highly selective inhibitor of protein phosphatase 2B (PP2B; calcineurin), has been developed. The absolute stereochemistry of the enantiomers was determined by X‐ray crystallographic analysis. Optically pure NCA derivatives that had various substituents at the C1 position were synthesized in a similar manner. The PP2B‐inhibitory activities of NCA‐01 and its derivatives were independent of the enantiomeric form. NCA‐01 dimethyl ester potently inhibited IL‐2 production in Jurkat cells.