Exploiting an Interrelationship between Axial and Planar Chirality in Natural Products Total Synthesis

在天然产物全合成中利用轴向手性和平面手性之间的相互关系

• 批准号: EP/G030669/1
• 负责人: David Harrowven
• 金额: $ 37.21万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG030669%2F1
• 关键词: Exploiting; Interrelationship; between; Axial; Planar

In recent years Nature has revealed some intriguing molecular targets with extraordinary stereochemical features. Most prominent are the vancomycins and related cyclic peptides, where different stereoelements (atom centred, axial, planar and cyclo stereoisomerism) co-exist within a single molecule. To confuse matters further, the various stereoelements may or may not be interrelated, making it hard to apply standard nomenclature when describing such entities. We believe that in many cases planar chirality rather than axial chirality is the important determinant differentiating two diastereoisomers of a given natural product. Our plan is to demonstrate this by using a radical induced transannular ring contraction under kinetic control to prepare a planar chiral phenanthrene within a macrocyclic structure. This will exist as two distinct diastereoisomers at room temperature, each with different faces of the phenanthrene enumbered by the encircling macrocycle. A high energy barrier for isomerisation will ensure that planar chirality is preserved on conversion of the phenanthrene to a biaryl. The latter will automatically be create with the correct axial-chirality, as these two stereoelements are interrelated. To the best of our knowledge this tactic has never previously been exploited in the context of total synthesis.

近年来，《自然》杂志揭示了一些具有非凡立体化学特征的有趣分子靶标。最突出的是万古霉素和相关环肽，其中不同的立体元件（原子中心、轴向、平面和环立体异构体）共存于单个分子内。更令人困惑的是，各种立体元素可能相互关联，也可能不相互关联，这使得在描述此类实体时很难应用标准术语。我们认为，在许多情况下，平面手性而不是轴向手性是区分给定天然产物的两种非对映异构体的重要决定因素。我们的计划是通过在动力学控制下使用自由基诱导的跨环收缩来证明这一点，以在大环结构内制备平面手性菲。在室温下，这将作为两种不同的非对映异构体存在，每种异构体具有由环绕大环编号的菲的不同面。异构化的高能垒将确保菲转化为联芳基时保留平面手性。后者将自动以正确的轴向手性创建，因为这两个立体元素是相互关联的。据我们所知，这种策略以前从未在全合成的背景下被利用过。