The Total Synthesis of 6-Hydroxypunctaporonin E

6-羟基点孔蛋白E的全合成

• 批准号: 7806918
• 负责人: Martin John McLaughlin
• 金额: $ 3.99万
• 依托单位: SWISS FEDERAL INST OF TECH (ETH ZURICH)
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-19 至 2012-07-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7806918
• 关键词: Acids; Alder plant; Antibiotics; Bacillus subtilis; Bacteria; Bacterial Infections; Biological; Biological Factors; Chemistry; Development; Diels Alder reaction; Evaluation; Future; Genus staphylococcus; Goals; Growth; Medicine; Oxidants; Pharmaceutical Preparations; Property; Research; Resistance development; Route; catalyst; design; fungus; novel; public health relevance

DESCRIPTION (provided by applicant): The goal of the proposed research is to define the first synthetic route toward 6-hydroxypunctaporonin E, a polycyclic natural product. 6-Hydroxypunctaporonin E was isolated from the fungicolous fungi Pestalotiopsis disseminata, collected in the state of Georgia, and was shown to have antibiotic properties inhibiting the growth of Bacillus subtilis and Staphylococcus aureas.[1] The proposed synthetic route includes an unusual example of the Diels-Alder reaction between a vinylcyclobutene and a dihydrofuranone. Included with the synthetic goal are the design of a novel chiral Lewis acid for Diels-Alder chemistry, and the study of a 6-hydroxypunctaporon E conjugate. PUBLIC HEALTH RELEVANCE: The development of broadly applicable antibiotic medicines is one of mankind's noteworthy accomplishments of the last century. Unfortunately, bacteria have begun to develop resistance to common medications used in the treatment of bacterial infections. As a result there is a continued need for research into the synthesis and biological evaluation of new compounds with antibiotic properties, to better understand their potential as new antibiotics of the future.

描述（由申请人提供）：拟议研究的目标是确定6-羟基五针皂苷E（一种多环天然产物）的第一条合成路线。6-从采集于格鲁吉亚州的真菌寄生性真菌播散拟盘多毛孢中分离出羟基凤仙花素E，并显示其具有抑制枯草芽孢杆菌和金黄色葡萄球菌生长的抗生素特性。[1]所提出的合成路线包括乙烯基环丁烯和二氢呋喃酮之间的Diels-Alder反应的不寻常的例子。包括与合成目标是一个新的手性刘易斯酸的Diels-Alder化学的设计，和6-羟基punctaporon E共轭物的研究。 公共卫生关系：广泛应用的抗生素药物的开发是上个世纪人类值得注意的成就之一。不幸的是，细菌已经开始对用于治疗细菌感染的常用药物产生耐药性。因此，持续需要研究具有抗生素特性的新化合物的合成和生物学评价，以更好地了解它们作为未来新抗生素的潜力。