SYNTHESIS OF CLAVULACTONE--A POTENTIAL ANTITUMOR AGENT

一种潜在的抗肿瘤药物克拉内酯的合成

• 批准号: 6294196
• 负责人: NATALIE A HAWRYLUK
• 金额: $ 3.33万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6294196
• 关键词: analog; animal extract; antineoplastics; chemical synthesis; coral; diterpenes; drug design /synthesis /production; stereochemistry; stereoisomer

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.

本研究的具体目标是发展一种高效的、对映选择性的克拉内酯合成方法。棒内酯是从一种未鉴定的棒孢属植物中分离得到的，属于海洋二萜类化合物dolabellane类。这些二萜类化合物含有特征性的反式双环[9.3.0]十四烷骨架。所提出的合成涉及使用立体定向三组分偶联过程形成四取代甲硅烷基烯醇醚，然后通过刘易斯酸催化的碳环闭合形成骨架。克拉内酯对埃利希腹水癌（EAC）细胞显示出细胞毒性，IC 50 8 μ g/mL，这使其成为抗肿瘤剂的潜在先导。高效的合成将允许类似物以及结构相关的天然产物的制备和生物学评价。