一系列新型三环二萜的合成与抗肿瘤活性研究

对活性天然产物(+)-7-deoxynimbidiol非对映异构体的外消旋体cis-(±)-7-deoxynimbidiol进行了合成和衍生, 共得到了8个新型三环二萜化合物; 对合成的新化合物进行了抗肿瘤活性的实验研究, 其中化合物5d对人体乳腺癌瘤株MCF7表现出了较强的抑制作用(IC50=7.49 μg/mL), 可能作为新型抗肿瘤药物先导化合物.

Synthesis and Anti-tumor Activities of a Series of Novel Tricycle Diterpenes

The tri-ring diterpenes with trans-configuration showed the anti tumor potency from many previous inverstigations, but the research for the tri-ring diterpene with cis-configuration has not been regarded so far. During our chemical studies on the bioactive compounds from the plants, a novel tri-ring diterpene (+)-7-deoxynimbidiol which attracts our intensive interest for its good anti-tumor activity was isolated from Celastrus hypoleucus. cis-(±)-7-Deoxynimbidiol(compound 4), the diastereoisomer of (+)-7-deoxynimbidiol, was total synthesized via eight-step reactions with geranic acid as the starting material, and modified by etherification of the phenolic hydroxyl with the substituted benzyl bromide. Eight novel tri-ring diterpenes(compounds 5a—5h) were obtained. The anti-tumor activities of all the new compounds were evaluated. Compound 5d was found to have potency against the cultured human-tumor cell line MCF7(IC50=7.49 μg/mL). The fluorine atom on the benzyl group was speculated to enhancethe anti-tumor activities.