Design And Synthesis Of Euphorbia Factor L₃Derivatives

Macrocyclic diterpenoid ester compounds in natural products, characterized bynovel and complicated structure, high oxygenation and multi-functional group as wellas distinctive physiological activity and pharmacological effect, are usuallyconsidered as leading compounds by domestic and foreign scholars in the treatment ofhuman diseases, especially tumors, AIDS, etc. In recent years, such research hasdeveloped rapidly. So far, more than600macrocyclic diterpenoid ester compoundsunder20categories such as taxanes and halberd alkanes have been reported separatedand identified. What’s more, new compounds and Macrocyclic diterpenoid skeletonare still under discovery.Lathyrane ester is one kind of macrocyclic diterpenoid ester compounds. As it isdifficult to obtain lathyrane ester in natural products, relevant studies on its activityand structural relation are few. Its skeleton is composed of one pentabasic ring andone hendecanal ring, and meanwhile, a cyclopropane is combined on C-9and C-11positions. It is a macrocyclic diterpenoid skeleton with high activity, and its maternalalcohol mainly includes Lathyrol, Ingol and Jolkinol. In the existing studies onbiological activity, scholars have found that such compounds have toxicity effect onmany kinds of tumor cells in anti-tumor activity, especially multi-drug resistance intumor treatment. Such kinds of compounds have showed higher active values.With Euphorbia factor L₃（Lathyrane ester compound, more contents in TCMsemen euphorbiae） as the leading compound, we have retained the active-structureskeleton of leading molecule, and meanwhile rationally introduced ester groups, thusobtained new Euphorbia factor L₃derivatives by chemical synthesis. In this paper, itdesigns and synthesizes FIVE series of new Euphorbia factor L₃derivatives:（1）C-5-hydroxy mono-substituted derivatives,（2） C-3,C-5hydroxyl substitutedderivatives of the same,（3） C-3, C-5hydroxyl substituted derivatives of different,（4）C-12,15epoxide derivative,（5） C-12,15epoxide isomers derivatives, in attempts to find out the methods for Latnyrane-type anti-tumor multi-drug resistance activecompounds, thus make contributions to illustration of relationship between structureand activity, and to preliminary discussion of mechanism. Furthermore, it aims to laya scientific foundation for the development of such potential drugs.