New Methods for Synthesis of Bioactive Terpenes

本研究项目由合成有机化学项目资助。皮尔森博士将开发基于过渡金属-烯烃配合物的新型合成试剂。这些复合物促进了现代农业所用材料中复杂环系统的构建。本研究围绕聚烯烃-过渡金属配合物作为构建季碳中心的反应中间体展开。在这些研究中开发的方法将应用于一些具有生物活性的萜类天然产物的全合成。环己二烯配合物可用于合成木霉酚和疣芦醇等木霉烯类化合物，以及合成二萜类甾二酮和阿霉素。每一类化合物都具有抗菌、抗真菌和/或抗病毒活性。新发现的二烯基和二烯铁配合物的反应，其中一个悬垂的烯烃在碳-碳键形成过程中偶联到有机金属单元。将研究这些反应的范围和合成应用。研究了一种合成紫杉烷衍生物的新方法。这些化合物，特别是紫杉醇，作为抗肿瘤药物显示出非凡的前景。本提案中描述的合成方法旨在通过高度取代的锡烯酸酯与三羰基（1,3 -二甲基-4-甲氧基环己二烯基）六氟磷酸铁的反应，然后通过内部的pinacol反应将八元环固定到位，从而确定碳骨架的主要部分。

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.