一系列新型三环二萜的合成与抗肿瘤活性研究

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

对活性天然产物(+)-7-deoxyn imb id iol非对映异构体的外消旋体cis-(±)-7-deoxyn imb id iol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=7.49μg/mL),可能作为新型抗肿瘤药物先导化合物.

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 enhance the anti-tumor activities.