Natural Product Synthesis and Synthetic Methodology

天然产物天生优化了生物相互作用，并占据了与大多数合成分子不同的化学空间。因此，它们为有机化学和疾病治疗的进步提供了无与伦比的灵感来源。我们不仅认为自然产品本身是有价值的商品，而且还将其视为发明更广泛的新的、使之成为可能的合成技术的推动力。 因此，拟议的工作旨在简化面向目标的综合，并开发用于构建特权结构的强大的新方法和战略。目标是官能化的氧杂环(内酯、四氢呋喃、伽马-吡喃和环过氧化氢)，具有不寻常的结构特征和高度寻求的生物学特性，包括抗肿瘤、抗炎和抗疟疾活性。每一项目标都带来了具体的挑战，为解决选择性、阶梯经济和整体效率等关键问题提供了充足的机会。其中一些化合物(如异黄素A-B、多奈素A和副内酯A)也为我的实验室最近发现的一些新反应提供了一个试验场。 进行这项研究的学生除了在合成有机化学方面具有广泛的专业知识外，还会发展解决问题的技能。我的团队几乎所有成员都通过积极参与多相不对称催化的合作研究而进一步受益，这涉及到表面科学、有机合成和计算化学的结合。因此，确保了跨学科环境中基础广泛的培训。

Natural products are inherently optimized for biological interactions and occupy chemical space distinct from that of most synthetic molecules. As such they represent an unparalleled source of inspiration for advances in organic chemistry and disease treatment. We regard natural products not only as valuable commodities per se, but also as a driving force for invention of new and enabling synthetic technologies of broader scope. Hence, the proposed work aims at streamlining target-oriented synthesis and the development of powerful new methods and strategies for constructing privileged structures. The targets are functionalized oxacycles (lactones, tetrahydrofurans, gamma-pyrones and cyclic peroxides) having unusual structural features and highly sought biological properties, including antitumor, anti-inflammatory and antimalarial activities. Each target instills specific challenges that provide ample opportunity for addressing key issues such as selectivity, step-economy and overall efficiency. Some of them (e.g. anomaxins A-B, donnaienin A and paracaseolide A) also provide a testing ground for some new reactions discovered very recently in my laboratories. Students who carry out this research develop problem-solving skills along with extensive expertise in synthetic organic chemistry. Nearly all members of my group further benefit through active participation in collaborative research on heterogeneous asymmetric catalysis, which involves a combination of surface science, organic synthesis and computational chemistry. Thus, broad-based training in an interdisciplinary setting is ensured.