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Reaction Sequencing: A concise asymmetric approach to the antibacterial pleuromutilin

Final Report Summary - SEQUENCING (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.