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化疗的关键因素。 由于细菌耐药性问题的日益严重，对新的抗细菌/抗真菌化合物存在巨大需求。 本文提出的项目是一个串联的papulacandins，一类有效的单糖，双糖和三糖抗真菌抗生素的合成/生物学研究。 我们的研究围绕着一个独特的从头不对称合成方法的papulacandin环系统，这应该可以很容易地获得这些二和三嗪。 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。 获得丘疹素环系统和类似物将使我们能够探测这种抗真菌剂的作用机制，并最终允许发现新的更有效和更稳定的抗真菌剂。 此外，这些生物学研究还应该导致新的抗菌，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.