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至关重要，因为这些分子在这些领域很普遍。可以在少数步骤中实现这些化合物的合成，并且在环上具有很高灵活性的方法特别有价值，因为它们为多样化功能化的分子提供了快速的进入。该项目旨在使用噻吩S，S-二氧化物作为关键构建块开发新的，高度模块化的方法，以合成有机环系统。噻吩S，S-二氧化物可以轻松地从易于使用的硫硫代硫苯甲环系统中制备在单个氧化步骤中，但在很大程度上被忽略为环合成工具。我们认识到他们被忽视的能力经历了“级联”环加成过程和SO2丢失以形成新的有机环的能力。我们建议发明多种方法来在单个反应瓶中组装该级联的底物，实际上可以实现有机环靶标的一步“定制”合成。我们还将探索将这种化学作用用于合成生物活性天然产品的方法。在某些情况下，这些分子以前需要10-20步合成，但是使用我们的策略可以在2-5个合成转换中制备。这代表了最先进的一项重大进步，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反应的不对称版本，以便化学家可以准备产物分子的单个“手”（对映异构体）。这对于药物化学应用至关重要，因为分子的不同“手”可​​以表现出不同的生物学特性。总而言之，该项目将为使用噻吩S，S-Dioxides在重要环系统的模块化合成中提供许多机会，以及天然产品脚手架的快速进入。