Synthesis of Papulacandins A-D; New Antifungal Analogs

Papulacandins A-D 的合成；

• 批准号: 6435496
• 负责人: GEORGE A O'DOHERTY
• 金额: $ 14.96万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6435496
• 关键词: aminoglycoside antibiotics; analog; antifungal antibiotics; biological products; cell line; disaccharides; drug design /synthesis /production; drug screening /evaluation; enzyme inhibitors; glycosidases; glycosyltransferase; ketal; monosaccharides; oligosaccharides; pharmacokinetics; spirane

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.

了解寡糖结构如何控制这些细胞识别事件对治疗许多传染病具有重大影响。 此外，了解寡糖结构和生物合成是发现新化学疗法的关键要素。 由于细菌耐药性的日益严重，因此非常需要新的抗菌/抗真菌化合物。 本文提出的项目是对丘疹蛋白，一类有效的单，二糖抗真菌抗生素的串联合成/生物学研究。 我们的研究围绕着对丘疹环蛋白环系统的独特的从头不对称的合成方法，该方法应该可以轻松访问这些DI和三糖。 此外，这种方法将允许简单地访问此类天然产品的不自然类似物，并可以轻松筛选活动。 访问Papulacandin环系统和类似物将使我们能够探究该抗真菌剂的作用机理，并最终允许发现新的更有效，更稳定的抗真菌剂。 此外，这些生物学研究还应导致新的抗菌，抗癌和抗病毒化合物。