白花前胡丙素C-3′和C-4′反式结构类似物的半合成白花前胡丙素C-3′和C-4′反式结构类似物的半合成

目的对白花前胡丙素［(+)-praeruptorin A］进行结构修饰,半合成C-3′和C-4′反式结构类似物,寻找活性化合物。方法首先从白花前胡(Peucedanum praeruptorum)根中分离得到白花前胡丙素,从白花前胡丙素出发,运用碱水解及各种酰化反应,半合成各种结构修饰产物。结果首次合成了17个白花前胡丙素C-3′和C-4′反式结构类似物,通过IR,¹HNMR,MS等方法确定它们的结构。结论17个化合物均为新化合物,其中一些新化合物有显著的钙离子拮抗活性,首次证明C-3′和C-4′反式结构的这类化合物同样具有活性。

Semi-synthesis of derivatives with C-3' and C-4' trans-configuration from (+)-praeruptorin A]

AIM: In order to compare the calcium antagonist activity between the derivatives of (+)-praeruptorin A with C-3' and C-4' cis-configuration and trans-configuration, and to look for new active compounds, some derivatives with C-3', C-4' trans-configuration of (+)-praeruptorin A were semi-synthsized. METHODS: (+)-Praeruptorin A was isolated from the root of Peucedanum praeruptorum. Basic hydrolysis of (+)-praeruptorin A was carried out. From the alkaline hydrolysis product (2), eight new products (5-12) with C-3', C-4' trans-configuration were semi-synthsized whose C-3' was linked to angeloyloxy and C-4' was linked to various acyloxy, using respective acids as acylating agents, DCC as a dehydrant, DMAP as catalyst. From the alkaline hydrolysis product (4), five new products (13-17) with C-3', C-4' trans-configuration were obtained whose C-3', C-4' is linked to various same acyloxys, using respective acids as acylating agents, DCC as dehydrant, DMAP as catalyst. Also from the alkaline hydrolysis product (4), using respective acyl chlorides as acylating agents, anhydrous dichloromethane containing minor pyridine as a solvent, the improved Schotten-Baumann reactions were carried out, two new products (18, 20) with C-3', C-4' trans-configuration were obtained whose only C-3' linked to acyloxy and two other new products (19, 21) with C-3', C-4' trans-configuration were obtained whose C-3' and C-4' linked two acyloxys. The structures of all the products were elucidated by spectral analyses including IR, 1HNMR and EIMS. The calcium antagonist activity of all of the products were tested by inhibition of the systole of rat artery ring. RESULTS: Seventeen compounds with C-3', C-4' trans-configuration were semi-synthesized from (+)-praeruptorin A for the first time and their calcium antagonist activity were evaluated. CONCLUSION: All of the derivatives were new compounds. Bioactivity assay indicated that some new compounds with C-3', C-4' trans-configuration showed obvious calcium antagonist activity, but they are not as strong as (+)-praeruptorin A. The activity of some products was shown to be similar to that of the derivatives with C-3', C-4' cis-configuration for the first time.