New Methods for Synthesis of Bioactive Terpenes

该研究项目是由合成有机化学项目资助的。皮尔逊博士将开发基于过渡金属-烯烃络合物的新合成试剂。这些复合体有助于构建现代农业所用材料中的复杂环系。这项研究围绕使用聚烯烃过渡金属络合物作为活性中间体来构建季碳中心。在这些研究中开发的方法学将应用于一些具有生物活性的萜类天然产物的全合成。环己二烯亚铁配合物可用于合成毛霉酚和鞭草酚等三氯乙烯类化合物，以及用于合成二萜类化合物千金藤酮和除草剂。这些化合物中的每一类都显示出抗菌、抗真菌和/或抗病毒活性。新发现的二烯基和二烯铁络合物的反应，其中一个侧链烯烃在碳-碳键形成过程中偶联到有机金属单元上，将被详细研究。将对这些反应和相关反应的范围和合成应用进行研究。将研究合成紫杉烷衍生物的新方法。这些化合物，特别是紫杉醇，显示出作为抗肿瘤药物的特殊前景。本建议中描述的合成方法旨在通过高取代度的锡烯醇酸与tricarbonyl(l，3-dimethyl-4-methoxycyclohexadienyl)iron六氟磷酸盐反应，然后进行内部频那醇反应，将碳骨架的主要部分固定在适当的位置。

This research program is being funded by the Synthetic Organic Chemistry Program. Dr. Pearson will develop new synthetic reagents based upon transition metal-olefin complexes. These complexes facilitate the construction of complicated ring systems found in the materials used by modern agriculture. This research revolves around the use of polyolefin-transition metal complexes as reactive intermediates for the construction of quaternary carbon centers. The methodology developed during these studies is to be applied in total synthesis of a number of biologically active terpenoid natural products. Cyclohexadienyliron complexes are to be used in the synthesis of trichothecenes such as trichodermol and verrucarol, and in synthesis of the diterpenoids stemodinone and aphidicolin. Each of these classes of compound show antibacterial, antifungal and/or antiviral activity. Newly discovered reactions of dienyl- and diene iron complexes, in which a pendant olefin is coupled to the organometallic unit in a carbon-carbon bond forming process are to be studied in detail. The scope and synthetic applications of these and related reactions will be investigated. A new approach to the synthesis of taxane derivatives will be investigated. These compounds, in particular taxol, show exceptional promise as antitumor agents. The synthetic approach described in this proposal aims to set in place the major part of the carbon skeleton via the reaction of a highly substituted tin enolate with tricarbonyl(l,3-dimethyl-4-methoxycyclohexadienyl)iron hexafluorophosphate, followed by an internal pinacol reaction to set in place the eight-membered ring.