Total Synthesis of Cytotoxic Garcinia Natural Products

细胞毒性藤黄果天然产物的全合成

• 批准号: 6895814
• 负责人: Tristan H Lambert
• 金额: $ 4.4万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-24 至 2006-04-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895814
• 关键词: Diels Alder reaction; biological products; chemical addition; chemical reaction; chemical synthesis; combinatorial chemistry; cytotoxicity; drug design /synthesis /production; evaporation; neoplasm /cancer pharmacology; neoplastic cell; plant extracts; predoctoral investigator

DESCRIPTION (provided by applicant): Many members of the Garcinia family of natural products have been shown to display significant cytotoxicity against a range of cancer cell lines. The goal of the proposed research is to develop a short and efficient synthesis of a member of this family, gaudichaudiic acid G. A key step in the proposed synthesis is a novel one-pot, three component coupling reaction. This sequence, which involves a Diels-Alder reaction, aldol condensation, and hetero-Michael addition, will allow for the exceedingly facile preparation of the tricyclic core common to the Garcinia xanthonoids. Coupling of this core fragment to a complex but readily prepared phenolic fragment will complete the total synthesis of guadichaudiic acid G. In addition, coupling of this core to alternative phenolic fragments will allow rapid access to additional members of this family including naturally occurring morellic acid and scortechinone B as well as a potentially limitless number of unnatural analogues. In this way, a library of garcinia-type products will be generated and assayed for cytotoxicity against cancer cell lines with the ultimate goal being to identify a compound with superior biological activity.

描述（由申请人提供）：藤黄属天然产物家族的许多成员已被证明对一系列癌细胞系表现出显着的细胞毒性。本研究的目标是开发一种简短而高效的合成方法，该家族的成员高迪乔迪酸 G。所提出的合成的关键步骤是一种新颖的一锅三组分偶联反应。该序列涉及第尔斯-阿尔德反应、羟醛缩合和杂迈克尔加成，将允许非常容易地制备藤黄类黄酮类化合物共有的三环核心。将该核心片段与复杂但易于制备的酚片段偶联将完成愈创二酸 G 的全合成。此外，将该核心片段与替代酚片段偶联将允许快速获得该家族的其他成员，包括天然存在的羊肚菌酸和scortechinone B 以及潜在无限数量的非天然类似物。通过这种方式，将生成藤黄类产品库并分析其对癌细胞系的细胞毒性，最终目标是鉴定具有优异生物活性的化合物。