SEQUENCING · Reaction Sequencing: A concise asymmetric approach to the antibacterial pleuromutilin
7РП — „Хора“ (Действия „Мария Кюри“)
- Период
- 2008-03-03 → 2008-11-02
- Финансиране от ЕС
- 169 391 €
- Участници
- 1
- Схема
- MC-IEF
Линиите свързват координатора с партньорите.
Накратко на български
Химическият синтез на плеуромутилин (антибактериално вещество) се изследва чрез нов метод за бързо създаване на сложни молекулни структури. Това помага за разработването на нови лекарства, които да се справят с нарастващата резистентност към антибиотиците.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Reaction Sequencing: A concise asymmetric approach to the antibacterial pleuromutilin
Summary and future work We have exploited a SmI2–mediated dialdehyde cyclization cascade in an approach to the pleuromutilin framework. The reaction proceeds with complete sequence integrity and with excellent control during the construction of four, contiguous stereocenters. The product of the cascade reaction can be converted to a valuable pleuromutilin precursor. Due to the resignation of the Fellow our plans to apply the approach in the asymmetric synthesis of pleuromutilin analogues not accessible from the natural product were not fulfilled. Socio–economic impact of the project We have developed new approaches to reaction sequencing that allow molecular complexity to be increased in a single step. This is an important, current area of organic synthesis and our studies have made a significant contribution to the field. The provision of new, sequential organic reactions will benefit the synthetic community including those working in the pharmaceutical, agrochemical and fine–chemicals industries in Europe, by allowing drugs and other active agents to be constructed rapidly saving time and other resources whilst potentially minimizing waste. The Fellowship has also resulted in the development of a flexible approach to pleuromutilin analogues. Such an approach in important as resistance to antibiotics becomes a major concern worldwide. This project has paved the way for access to analogues of the natural product with drug–like properties that cannot currently be prepared and may lead to future therapeutics based on the pleuromutilin scaffold. The proposed work will therefore have widespread benefits for everyone in the European Community.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Resistance to antibiotics is a major concern worldwide and has led to an urgent need to identify antibacterial agents with modes of action distinct from the established classes. The antibacterial natural product pleuromutilin is such a candidate and has been the focus of biological and medicinal studies in recent years. Unfortunately, pleuromutilin has poor pharmacokinetic properties and the compound is readily metabolised by enzymes. Although the natural product itself is not a very good drug, analogues of pleuromutilin look promising. This project will provide access to analogues of the natural product with drug–like properties that cannot currently be prepared, thus paving the way for new therapeutics based on the pleuromutilin scaffold that will improve the quality of life of people in the European Community We will develop new stereoselective processes in which the sequencing of a number of individual chemical reactions allows access to a complex, cyclic system in one synthetic step, using one reagent. We will assemble the skeleton of the antibacterial, pleuromutilin using the lanthanide reagent SmI2 to orchestrate the reaction sequencing so that we get a high yield while achieving good control over the stereochemistry of the product. Our proposal is that different parts of a molecule will react one after the other in an ordered sense, like toppling dominos, until a pleuromutilin–like product is reached. The results of our work will be of interest to synthetic chemists working in academic and industrial laboratories in Europe and throughout the world. The specific objectives of the multidisciplinary project are: - to investigate the individual reaction steps of the proposed sequence using model compounds. - to develop reaction sequencing in a concise synthesis of the tricyclic core of pleuromutilin. - to develop the first asymmetric route to pleuromutilin. - to prepare analogues of pleuromutilin and to carry out their preliminary biological evaluation.
Оригинален текст от CORDIS (на английски).
Участници
- THE UNIVERSITY OF MANCHESTER · ManchesterКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз