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: 6740373
• 负责人: Tristan H Lambert
• 金额: $ 4.11万
• 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/6740373
• 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）：已经证明，藤黄家族的许多成员在一系列癌细胞系中表现出明显的细胞毒性。拟议的研究的目的是开发该家族成员的短而有效的合成，即高迪克酸G。拟议合成的一个关键步骤是一种新型的单锅，三个成分耦合反应。该序列涉及Diels-Alder反应，醛凝结和杂音 - 莫克莱的添加，将允许对藤黄型千巢类似的三轮车核心进行非常便捷的制备。该核心碎片与复杂但容易准备的酚类碎片的耦合将完成瓜迪辅酸G的全面合成。此外，将该核心与替代酚类碎片耦合将允许快速访问该家族的其他成员，包括自然存在的莫雷酸和斯科甲酮B，以及无限的无限数量的不确定数量。这样，将生成和测定一个针对癌细胞系的细胞毒性的藤黄型产品库，其最终目标是鉴定具有出色生物学活性的化合物。