Synthesis of Papulacandins A-D; New Antifungal Analogs

了解寡糖结构如何控制这些细胞识别事件对许多感染性疾病的治疗具有重要意义。此外，了解寡糖结构和生物合成是发现新的化疗方法的关键因素。由于细菌耐药性问题日益严重，人们对新型抗菌/抗真菌化合物的需求很大。本文提出的项目是对丘疹菌素的合成/生物研究，丘疹菌素是一类有效的单糖、双糖和三糖抗真菌抗生素。我们的研究围绕着一种独特的不对称合成方法来合成丘皮菌素环体系，这种方法可以很容易地获得这些二糖和三糖。此外，这种方法将允许简单地获得这类天然产物的非天然类似物，并允许容易地筛选活性。进入丘疹霉素环系统和类似物将使我们能够探索这种抗真菌药物的作用机制，并最终允许发现新的更有效和更稳定的抗真菌药物。此外，这些生物学研究也应该导致新的抗菌，抗癌和抗病毒化合物。

Understanding how oligosaccharide structure controls these cellular recognition events has major implications for the treatment of many infectious diseases. Furthermore, understanding oligosaccharides structures and bio-synthesis are critical elements for discovering new chemotherapies. Due to the growing problem of bacterial resistance, there is a great need for new antibacterial/antifungal compounds. The project proposed herein is a tandem synthetic/biological investigation of the papulacandins, a class of potent mono-, di-, and trisaccharide antifungal antibiotics. Our study revolves around a unique de novo asymmetric synthetic approach to the papulacandin ring system, which should allow for easy access to these di and trisaccharides. In addition, this approach will allow simple access to unnatural analogs of this class of natural products and allow for easy screening for activity. Access to the papulacandin ring system and analogs will enable us to probe the mechanism of action to this antifungal agent and ultimately allow for the discovery of new more potent and stable antifungal agents. Additionally, these biological studies should also lead to new antibacterial, anticancer and antiviral compounds.