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Synthesis of complex aminoacids and the microsclerodermins

复杂氨基酸和微硬皮素的合成

基本信息

批准号：
EP/I010343/1
负责人：
Timothy Donohoe
金额：
$ 31.35万
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：
2010
资助国家：
英国
起止时间：
2010 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FI010343%2F1
关键词：
Synthesis complex aminoacids microsclerodermins

项目摘要

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.

由于化学工业对选择性、高效和环境友好的化学过程的需求不断增加，开发新的反应是现代合成有机化学最紧迫的目标之一。我们的目标是开发方法，将允许快速和有效的合成复杂的氨基酸含有天然产物具有有趣的生物活性。近年来，我们已经建立了氧化烯烃的方法的知识，并在这样做的过程中提供了构建块，这些构建块是完成氨基酸合成的完美材料。这个建议的目的是说服读者，（i）天然产物微硬皮病蛋白的合成（其是一种有效的抗肿瘤剂）是一个有价值的和高影响的研究领域;（ii）合成本身将推动可用于许多其他应用的新方法和试剂的开发，特别是在构建复杂的氨基酸和肽中;（iii）我们拥有该等类型化合物的经验及专业知识，以确保合成成功及完成。为了适应这样一项复杂的任务，我们可以使用各种各样的生物筛选，特别是那些寻找抗癌活性的筛选，并将对最终化合物和途中形成的中间体进行测试。这将确保以相对适度的支出获得新科学信息的最大回报。该提案中描述的化学过程是有趣和有用的，因为它将使我们能够以短而有效的顺序制备一种以前从未制备过的复杂天然产物。我们将被迫探索几种有机方法的局限性，这将导致更强大的烯烃氧化方法，并通过一种全新的途径制备肽。除了这种分子所带来的纯粹的化学挑战之外，筛选它和它的前体，以获得已报道的令人兴奋的生物活性，肯定是一项有价值的任务。本文描述的化学是高影响力的，包含方法和合成的理想组合;它具有重要的备份计划（如肽和氨基醇的独立合成）和出版里程碑，并将揭示真正有趣和有用的反应，以及为PDRA提供出色的培训。我们也有合成和这些类型的分子的经验，以确保项目完成。