Development of Novel Ligands for Glutamate Receptors Using Natural Neurotoxins as the Structural Motif

Kaitocephalin因其对哺乳动物中枢神经系统中谷氨酸受体的拮抗作用而备受关注，有望成为研究谷氨酸受体功能和开发神经保护剂的有力候选药物。在本研究中，我们实现了甲头脑素的高效全合成，并伴随着新的合成方法的发展。我们还进行了其衍生物、结构简化类似物和其他神经活性氨基酸的合成，其SAR研究表明，kaitocephalin及其一些衍生物对NMDA受体具有有效的结合活性。

Kaitocephalin has attracted much attention due to its potent antagonist activity to glutamate receptors in mammalian CNS, and is expected to be a potent candidate as a tool to investigate the function of glutamate receptors as well as a leadto develop neuroprotecting agent. In this study, we have achieved the highly efficient total synthesis of kaitocephalin which was accompanied by the development of new synthetic methods. We also performed the synthesis of its derivatives, structurally simplifiedanalogs, and other neuroactive amino acids, whose SAR studies revealed that kaitocephalin and some of its derivatives exhibited potent binding activities to NMDA receptors.