Thiophene dioxides: Versatile tools for ring synthesis

二氧化噻吩：环合成的多功能工具

• 批准号: EP/X028674/1
• 负责人: Edward Anderson
• 金额: $ 58.29万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX028674%2F1
• 关键词: Thiophene; dioxides; Versatile; tools; ring

The synthesis of ring-containing organic molecules is of fundamental importance in medicinal chemistry and agrochemistry, as such molecules are widespread in these fields. Methods that can achieve the synthesis of these compounds in a handful of steps, and also with high flexibility in the substituents on the rings, are of particular value as they offer a rapid entry to diversely functionalised molecules. This project seeks to develop new, highly modular methods for the synthesis of organic ring systems, using thiophene S,S-dioxides as the key building blocks.Thiophene S,S-dioxides are easily prepared from the readily available sulfur-containing thiophene ring system in a single oxidation step, but have been largely ignored as tools for ring synthesis. We recognised their overlooked ability to undergo a 'cascade' process of cycloaddition and loss of SO2 to form a new organic ring. We propose to invent a number of methods to assemble the substrates for this cascade in a single reaction flask, in effect enabling a one-step 'tailored' synthesis of the organic ring targets. We will also explore ways to use this chemistry for the synthesis of bioactive natural products; in some cases, these molecules have previously required 10-20 step syntheses, but using our strategies these can be prepared in 2-5 synthetic transformations. This represents a major advance in the state-of-the-art, opening up new opportunities for the study of the biology of these molecules. Finally, we also plan to develop asymmetric versions of these cascades, such that chemists can prepare single 'hands' (enantiomers) of the product molecules. This is of key importance for medicinal chemistry applications, as different 'hands' of molecules can exhibit distinct biological properties.In summary, this project will deliver many opportunities for the use of thiophene S,S-dioxides in the modular syntheses of important ring systems, as well as rapid entries to natural product scaffolds.

含环有机分子的合成在药物化学和农业化学中具有根本的重要性，因为此类分子广泛存在于这些领域中。可以在几个步骤中实现这些化合物的合成，并且在环上的取代基中具有高灵活性的方法具有特别的价值，因为它们提供了快速进入双官能化分子的途径。该项目旨在开发新的、高度模块化的方法来合成有机环系统，使用噻吩S，S-二氧化物作为关键构件。噻吩S，S-二氧化物很容易从容易获得的含硫噻吩环系统在单一氧化步骤中制备，但在很大程度上被忽视作为环合成的工具。我们认识到它们被忽视的能力，即经历环加成和失去SO2形成新的有机环的"级联"过程。我们建议发明一些方法来组装在一个单一的反应烧瓶中的级联的基板，实际上使一个步骤的有机环目标的“定制”合成。我们还将探索使用这种化学方法合成生物活性天然产物的方法;在某些情况下，这些分子以前需要10 - 20步合成，但使用我们的策略，这些分子可以在2 - 5个合成转化中制备。这代表了最先进技术的重大进步，为研究这些分子的生物学开辟了新的机会。最后，我们还计划开发这些级联的不对称版本，这样化学家就可以制备产物分子的单一“手”（对映体）。这对于药物化学应用是非常重要的，因为不同的分子"手"可以表现出不同的生物学特性。总之，这个项目将为噻吩S，S-二氧化物在重要环系统的模块化合成中的应用提供许多机会，以及快速进入天然产物支架。