An Allenic Pauson-Khand Reaction, New Directions

艾伦尼克鲍森-坎德反应，新方向

• 批准号: 6824079
• 负责人: Kay M Brummond
• 金额: $ 10.51万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6824079
• 关键词: Allenic; Pauson; Khand; Reaction; New

EXCEED THE SPACE PROVIDED The broadly defined objectives of our research program focus on the discovery and development of new methods to prepare organic compounds in a more rapid and stereoselective manner Our program strives to validate these new methods by applying them to the synthesis of biologically relevant products Our research program has been concerned specifically with an allenic transition metal catalyzed Pauson-Khand reaction that provides access to a-alkylidene and 4-alkylidene cyclopentenones, two classes of compounds that were previously accessible only via multi-step sequences During the new funding period we will continue our examination of the scope and limitations of the allenic Pauson-Khand reaction by preparing interesting and diversely functionalized ring systems To further validate this method we will synthesize guanacastepene A Guanacastepene A is a potent antibiotic that has shown remarkable activity against methiciUin resistant S aureas and vancomycin resistant E faecalis We will also synthesize other members of the guanacastepene family Availability of guanacastepenes B through O has hampered biological assays thus a rapid synthesis to these compounds is needed We will synthesize suberosenone, a potent anticancer compound showing differential cytotoxicity against cancer cell lines We will synthesize 15-deoxy-D12,14-PGJ2 using a newly developed silicon-tethered allenic Pauson-Khand reaction 15-Deoxy-D12,14-PGJ2 is a ligand for the peroxisome proliferator activated receptor, which has been linked to a variety of disease states, including type 2 diabetes and obesity We will investigate the generality of the newly discovered transannular ring closing Nicholas reaction for formation of vicinal quaternary centers We expect that through these long-term investigations, that we will more thoroughly understand transition metal catalyzed carbon-carbon bond forming processes, with particular emphasis on aUenes, an underrepresented moiety in the synthetic chemists arsenal of functional groups PERFORMANCE SITE ========================================Section End===========================================

我们的研究计划的广泛定义的目标集中在发现和开发新的方法，以更快速和立体选择性的方式制备有机化合物我们的计划致力于通过将其应用于生物相关产品的合成来验证这些新方法我们的研究计划一直特别关注与联烯过渡金属催化的Pauson-Khand反应，该反应提供了一种-亚烷基和4-亚烷基环戊烯酮，两类化合物，以前只能通过多步序列访问在新的资助期间，我们将继续我们的范围和限制的检查，艾伦暂停-Khand反应通过制备感兴趣的双功能化的环系统为了进一步验证该方法，我们将合成guanacastepene A Guanacastepene A是一种有效的抗生素，已显示出显着的活性抗耐甲氧西林金黄色葡萄球菌和耐万古霉素粪肠球菌我们还将合成胍那卡斯烯家族的其它成员胍那卡斯烯B至O的可用性妨碍了生物测定，因此需要快速合成这些化合物。我们将合成对癌细胞系显示不同细胞毒性的有效抗癌化合物辛二烯酮。我们将合成15-脱氧-D12，14-PGJ 2使用新开发的硅系连的丙二烯Pauson-Khand反应15-脱氧-D12，14-PGJ 2是过氧化物酶体增殖物激活受体的配体，其与多种疾病状态有关，包括2型糖尿病和肥胖，我们将研究新发现的跨环闭合尼古拉斯反应的普遍性，邻位四元中心我们期望通过这些长期的研究，我们将更彻底地理解过渡金属催化的碳-碳键形成过程，特别强调烯烃，在合成化学家的官能团库中，一个代表性不足的部分性能网站=========================================