Improved synthesis and characterization of L-histidine norcantharimide, a novel potent protein phosphatase 2A inhibitor

Abstract

Abstract:

Improved synthesis and structure identification of L-histidine norcantharimide, a potent PP2A inhibitor was reported. Condensation between norcantharidin and L-histidine in 95% EtOH at reflux temperature affords L-histidine norcantharimide in 97.0% yield which is much higher compared with literature, and more importantly, the configuration is retained. The chemical structure of the compound was re-elucidated through IR, FAB-MS, ¹H NMR, ¹³C NMR and 2D NMR (¹H, ¹³C-COSY and HMBC), the fundamental physical data, including optical data being also firstly reported. Preliminary cytotoxicity evaluation showed that the target compound was probably more potent than norcantharidin against a panel of human cancer cell lines. Design and synthesis of amino acid (nor) cantharimides would provide a convenient and rational structure modification of (nor) cantharidin and open new avenues to explore new promising candidates.

Key words: Norcantharmide, Norcantharmide, Norcantharidin, Norcantharidin, L-Histidine, L-Histidine, ,

CLC Number:

R916.4

Supporting:

Da-Feng Chen, Yong Zou*, Yong-Qiang Li, Yu-Chen Cai, Li-Jian Xian. Improved synthesis and characterization of L-histidine norcantharimide,
a novel potent protein phosphatase 2A inhibitor[J]. .

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Improved synthesis and characterization of L-histidine norcantharimide,
a novel potent protein phosphatase 2A inhibitor

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