An Allenic Pauson-Khand Reaction, New Directions

描述（由申请人提供）：我们的研究项目的主要目标是发现和发展新的方法，以更快速和立体选择性的方式制备有机化合物。我们的计划努力通过将这些新方法应用于生物相关产品的合成来验证这些新方法。我们的研究项目一直特别关注一种异位过渡金属催化的Pauson-Khand反应，该反应提供了a-烷基烯和4-烷基烯环戊烯酮的途径，这两类化合物以前只能通过多步序列获得。在新的资助期内，我们将通过制备有趣的、不同功能化的环体系，继续研究异位Pauson-Khand反应的范围和局限性。为了进一步验证这一方法，我们将合成瓜纳卡斯丁烯A。瓜纳卡斯丁烯A是一种有效的抗生素，对耐甲氧西林金黄色葡萄球菌和耐万古霉素粪肠杆菌具有显著的活性。我们还将合成瓜纳卡斯丁烯家族的其他成员。guanacastepenes B到O的可用性阻碍了生物分析，因此需要快速合成这些化合物。我们将合成亚芥子酮，一种有效的抗癌化合物，对癌细胞具有不同的细胞毒性。我们将利用新开发的硅系链的异位Pauson-Khand反应合成15-脱氧- d12,14 - pgj2。15- deoxy - d12,14 - pgj2是过氧化物酶体增殖体激活受体的配体，与多种疾病状态有关，包括2型糖尿病和肥胖。我们将研究新发现的跨环闭合尼古拉斯反应在邻季中心形成中的普遍性。我们期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-碳键形成过程，特别强调烯，这是合成化学家的官能团库中代表性不足的部分。

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.