Thiophene dioxides: Versatile tools for ring synthesis

含环有机分子的合成在药物化学和农业化学中具有重要的基础意义，因为这些分子在这些领域广泛存在。能够在几个步骤中合成这些化合物的方法，并且在环上的取代基上具有很高的灵活性，因为它们提供了快速进入不同功能化分子的方法，因此具有特别的价值。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-二氧化物作为关键的构建模块。噻吩S，S-二氧化物很容易由现成的含硫噻吩环体系在一次氧化步骤中制备，但在很大程度上被忽视了作为环合成的工具。我们认识到它们被忽视的经历环加成和SO2损失的“级联”过程以形成新的有机环的能力。我们建议发明多种方法在单个反应烧瓶中组装该级联的底物，实际上可以一步“定制”合成有机环目标。我们还将探索如何利用这种化学合成具有生物活性的天然产物；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，这些可以在2-5合成转化中制备。这代表了最先进技术的一个重大进步，为这些分子的生物学研究开辟了新的机会。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品分子的单“手”（对映体）。这对于药物化学应用至关重要，因为不同的分子“手”可以表现出不同的生物学特性。总之，该项目将为在重要环体系的模块化合成中使用噻吩S，S-二氧化物以及快速进入天然产物支架提供许多机会。

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.