Synthesis of Papulacandins A-D; New Antifungal Analogs

Papulacandins A-D 的合成；

• 批准号: 6860062
• 负责人: GEORGE A O'DOHERTY
• 金额: $ 24.82万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6860062
• 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于许多传染病的治疗具有重大意义。 此外，了解寡糖结构和生物合成是发现新化疗的关键要素。 由于细菌耐药性问题日益严重，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白蛋白（一类有效的单糖、二糖和三糖抗真菌抗生素）的串联合成/生物学研究。 我们的研究围绕巴普拉坎定环系统的独特从头不对称合成方法展开，该方法应该可以轻松获得这些二糖和三糖。 此外，这种方法将允许简单地获得此类天然产品的非天然类似物，并允许轻松筛选活性。 获得巴普拉坎定环系统和类似物将使我们能够探究这种抗真菌剂的作用机制，并最终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产生新的抗菌、抗癌和抗病毒化合物。

项目成果

De novo formal synthesis of (-)-virginiamycin M2 via the asymmetric hydration of dienoates.

通过二烯酸酯的不对称水合从头正式合成 (-)-维吉尼亚霉素 M2。

• DOI: 10.1021/ol071145e
• 发表时间: 2007
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: Mortensen,MatthewS;Osbourn,JoshuaM;O'Doherty,GeorgeA
• 通讯作者: O'Doherty,GeorgeA

De Novo Asymmetric Syntheses of (+)-Goniothalamin, (+)-Goniothalamin oxide and 7,8-Bis-epi-Goniothalamin using Asymmetric Allylations.

（+） - 促性甲瓜素，（+） - 氧化促性腺素和7,8-Bis-epi-goniothalamin的从头不对称合成。

• DOI: 10.1016/j.tet.2009.03.097
• 发表时间: 2009-06-27
• 期刊: Tetrahedron
• 影响因子: 2.1
• 作者: Harsh P;O'Doherty GA
• 通讯作者: O'Doherty GA

De novo asymmetric syntheses of muricatacin and its analogues via dihydroxylation of dienoates.

通过二烯酸酯的二羟基化从头不对称合成 muricatacin 及其类似物。

• DOI: 10.1021/jo061057s
• 发表时间: 2006
• 期刊: The Journal of organic chemistry
• 作者: Ahmed,MdMoinuddin;Cui,Hu;O'Doherty,GeorgeA
• 通讯作者: O'Doherty,GeorgeA

The de novo synthesis of oligosaccharides: application to the medicinal chemistry SAR-study of digitoxin.

• DOI: 10.2174/156802608783378828
• 发表时间: 2008
• 期刊: Current topics in medicinal chemistry
• 影响因子: 3.4
• 作者: Maoquan Zhou;G. O'Doherty