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.

该研究建议的特定目的是开发一种有效而对映选择性的方法来合成锁骨酮。链霉酮从不明的克拉维亚氏菌中分离出来，属于海洋二萜的多贝氏剂类。这些双萜类化合物包含特征性的反式 - 双环[9.3.0]四烷骨骼。所提出的合成涉及使用立体特定的三个成分耦合过程形成骨骼，以形成四碱成立的silyl烯醇烯醇醚，然后是路易斯酸催化的碳环环环闭合。克拉维酮表现出针对Ehrlich腹水癌（EAC）细胞IC50 8 mug/ml的细胞毒性，这使其成为抗肿瘤剂的潜在铅。有效的合成将允许对类似物以及与结构相关的天然产物进行制备和生物学评估。