Synthesis of complex aminoacids and the microsclerodermins

点击翻译按钮获取中文摘要

The development of new reactions is one of the most pressing goals for modern synthetic organic chemistry because chemical industry has an ever increasing requirement for selective, efficient and environmentally friendly chemical processes. We aim to develop methods that will allow the rapid and efficient synthesis of complex aminoacid containing natural products with intriguing biological activity. Over recent years we have built up a knowledge of methods for oxidising alkenes and in so doing providing building blocks that are the perfect materials from which to accomplish the synthesis of aminoacids. The goal of this proposal is to convince the reader that (i) the synthesis of the natural product microsclerodermin (which is a potent anti-tumor agent) is a worthwhile and high impact area of research; (ii) that the synthesis itself will drive the development of new methods and reagents that are useful in many other applications, especially in the construction of complex aminoacids and peptides; (iii) we have the experience and expertise with these types of compound to ensure success and completion of the synthesis. As appropriate to such a complex undertaking, we have access to a wide variety of biological screens, especially those that search for anti-cancer activity, and tests will be performed on the final compound and intermediates formed en-route. This should ensure the biggest return of new scientific information for a relatively modest outlay. The chemistry described in this proposal is interesting and useful because it will enable us to prepare a complex natural product that has never been prepared before in a short and efficient sequence. We will be forced to explore the limitations of several organic methodologies as we go, and this will lead to more powerful methods for alkene oxidation and for the preparation of peptides via a fundamentally new route. In addition to the sheer chemical challenge posed by this molecule, it is surely a worthwhile task to screen it, and precursors to it, for the exciting biological activity that has been reported. The chemistry described herein is high impact and contains an ideal mix of methodology and synthesis; it has significant back-up plans (such as the stand-alone synthesis of peptides and aminoaclohols) and publication milestones, and will uncover really interesting and useful reactions as well providing an excellent training for a PDRA. We also have the experience with synthesis and with these types of molecules to ensure that the project is finished.