SYNTHESIS OF CLAVULACTONE--A POTENTIAL ANTITUMOR AGENT

本研究计划的具体目的是开发一种高效和对映选择性的方法来合成克拉维内酯。Clavulactone是从一种未知的Clavularia植物中分离得到的，属于海洋二萜中dolabellane类。这些二萜含有典型的反双环[9.3.0]十四烷骨架。提出的合成包括使用立体特异性三组分偶联过程形成骨架，形成四取代硅烯醇醚，然后由刘易斯酸催化碳环闭合。克拉维内酯对埃利希腹水癌（EAC）细胞具有细胞毒性，IC50为8马克/毫升，是一种潜在的抗肿瘤药物。有效的合成将允许制备和生物评价类似物以及结构相关的天然产物。

The specify aim of this research proposal is to develop an efficient and enantioselective approach for the synthesis of clavulactone. Clavulactone was isolated from an unidentified species of Clavularia and belong to the dolabellane class of marine diterpenoids. These diterpenoids contain characteristic trans-bicyclo [9.3.0] tetradecane skeletons. The proposed synthesis involves formation of the skeleton using a stereospecific three component coupling process for the formation of tetrasubstituted silyl enol ethers followed by Lewis acid catalysed carbocyclic ring closure. Clavulactone exhibits cytotoxicity against Ehrlich ascites carcinoma (EAC) cells, IC50 8 mug/mL, which makes it a potential lead for an anti- tumor agent. An efficient synthesis would allow for the preparation and biological evaluation of analogues as well as structurally related natural products.