An Allenic Pauson-Khand Reaction, New Directions

我们的研究项目的广泛目标集中在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的新方法。我们的项目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。我们的研究项目特别关注于一种异位过渡金属催化的Pauson-Khand反应，该反应可以获得a-烷基烯和4-烷基烯环戊烯酮,在新的资助期内，我们将通过制备有趣的和多样化功能化的环体系来继续研究异位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guanacastepena。guanacastepena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的E - faecalis显示出显著的活性我们还将合成瓜纳卡斯萜家族的其他成员，瓜纳卡斯萜烯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。我们将利用新开发的硅系异位Pauson-Khand反应合成15-deoxy- 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，它与多种疾病状态有关。我们将研究新发现的跨环闭合尼古拉斯反应的普遍性，以形成邻近的季中心。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，特别是对auene的研究。未被充分代表的那一部分官能团合成化学家阿森纳的表现 ======================================== 节结束 ===========================================

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===========================================