An Allenic Pauson-Khand Reaction, New Directions

描述（由申请人提供）：我们的研究计划的广泛定义的目标集中在新方法的发现和开发，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，该反应提供了获得α-亚烷基和4-亚烷基环戊烯酮的途径，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，我们将继续通过制备有趣的双官能化环体系来研究Allenic Pauson-Khand反应的范围和局限性。为了进一步验证该方法，我们将合成guanacastepene A。瓜那卡斯烯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球菌显示出显著的活性。我们还将合成guanacastepene家族的其他成员。胍那甾烯B至O的可用性阻碍了生物测定，因此需要快速合成这些化合物。我们将合成一种有效的抗癌化合物，对癌细胞系显示出不同的细胞毒性。我们将利用一种新开发的硅系连烯Pauson-Khand反应合成15-脱氧-D12，14-PGJ 2。15-脱氧-D12，14-PGJ 2是过氧化物酶体增殖物激活受体的配体，其与多种疾病状态相关，包括2型糖尿病和肥胖症。我们将探讨新发现的跨环闭合尼古拉斯反应的普遍性，形成邻位季中心。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-碳键形成过程，特别强调联烯，一个在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.