Total Synthesis of Cytotoxic Garcinia Natural Products

描述（由申请人提供）：藤黄属天然产品家族的许多成员已被证明对一系列癌细胞系显示出显著的细胞毒性。本研究的目的是开发一种短而高效的合成该家族成员gaudichadiic acid g的方法，其中合成的关键步骤是一种新的一锅三组分偶联反应。这个序列包括Diels-Alder反应，醛醇缩合和杂michael加成，可以非常容易地制备藤黄黄素共有的三环核心。将该核心片段偶联到一个复杂但容易制备的酚片段将完成番荔枝二酸g的全合成。此外，将该核心片段偶联到其他酚片段将允许快速获得该家族的其他成员，包括天然存在的苦参酸和scortechinone B，以及可能无限数量的非天然类似物。通过这种方式，将产生一个藤黄类产品的文库，并对癌细胞系进行细胞毒性测定，最终目标是鉴定出具有优越生物活性的化合物。

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.