蝙蝠葛苏林碱衍生物的合成及钙通道阻滞活性的研究

Synthesis and Ca^(2+)-channel Blocking Activities of Daurisoline Derivatives

目的 :合成蝙蝠葛苏林碱衍生物 ,寻找优良的钙通道拮抗剂。方法 :从蝙蝠葛粗总碱中分离出蝙蝠葛苏林碱 ,对其酚羟基进行醚化和酯化 (或选择性酯化 ) ,并测定其中一些衍生物的钙通道阻滞活性。结果 :合成了 15个蝙蝠葛苏林碱衍生物 ,其结构经IR、1HNMR、MS得到确证 ;6个衍生物具有一定的钙通道阻滞活性 ,化合物DS5具有比蝙蝠葛苏林碱、汉防己甲素和异博定更强的钙通道阻滞活性。结论

AIM:To search for novel potent compounds with Ca^(2+)-channel blocking activities.METHOD: Daurisoline was isolated from phenolic alkaloids of Menispermum dauricum DC. Ester and ether or selected ether was proceeding. The chemical structures of darisoline derivatives were identified based on IR,(()^(1)HNMR) and MS.RESULT: Preliminary pharmacological testing indicated that most of tested compounds exhibited higher calmodulin-antagonistic and Ca^(2+)-channel blocking activities than those of the parent compounds.CONCLUSION:It is suggested that compound DS_(5)may be developed as a potential Ca^(2+)-channel blocking agent and it is worthy to make a further study.