An Allenic Pauson-Khand Reaction, New Directions

艾伦尼克鲍森-坎德反应，新方向

• 批准号: 6989071
• 负责人: Kay M Brummond
• 金额: $ 20.5万
• 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 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6989071
• 关键词: Allenic; Pauson; Khand; Reaction; New

DESCRIPTION (provided by applicant): 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 methicillin 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 allenes, an underrepresented moiety in the synthetic chemists' arsenal of functional groups.

描述(由申请人提供)：我们研究计划的广泛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。我们的项目致力于通过将这些新方法应用于生物相关产品的合成来验证它们。我们的研究项目特别关注了异烯过渡金属催化的Pauson-Khandd反应，该反应提供了获得a-亚烷基和4-亚烷基环戊酮的途径，这两类化合物以前只能通过多步序列才能获得。在新的资助期间，我们将继续通过制备有趣的和不同功能的环系统来研究阿伦素Pauson-Khandd反应的范围和局限性。为了进一步验证这一方法，我们将合成鸟苷A。鸟苷A是一种有效的抗生素，对甲氧西林耐药的S金黄色葡萄球菌和万古霉素耐药的粪肠球菌显示出显着的活性。我们还将合成鸟苷家族的其他成员。鸟苷B到O的可用性阻碍了生物分析，因此需要对这些化合物进行快速合成。我们将合成Suberosenone，这是一种对癌细胞具有不同细胞毒性的有效抗癌化合物。我们将利用新开发的硅系留联烯Pauson-Khandd反应合成15-脱氧-D12，14-PGJ2。15-脱氧-D12，14-PGJ2是过氧化物酶体增殖物激活受体的配体，与多种疾病状态有关，包括2型糖尿病和肥胖症。我们将研究新发现的跨环闭合Nicholas反应形成邻近四元中心的共性。我们希望通过这些长期的研究，我们将更彻底地了解过渡金属催化的碳-碳键的形成过程，特别是联烯，这是合成化学家的官能团库中被低估的部分。