Studies in Natural Product Synthesis and Catalysis of Pericyclic Reactions

我们的研究项目融合了有机化学的基础研究和应用研究。基础研究的重点是开发新的合成方法和天然产物的全合成。我们研究计划的应用部分集中在设计和开发用于癌症治疗的新型杂化分子。在这项提议中描述的基础研究中，我们将继续合成两种天然产物--帕劳胺和病毒碱。帕劳胺是一种具有很强免疫抑制活性的海洋生物碱，由于其官能团的密度和具有挑战性的立体化学，是化学合成的一个极具挑战性的目标。我们正在开发Diels-Alder策略来设置中心碳环和共轭加成/氧化双闭合，以关闭分子中反式熔融的吡咯酰胺/胍缩醛部分。Virosaine是一种新分离的Secounega生物碱，是少数几个被认为通过[3+2]硝酮环加成生物合成的分子之一。我们正在开发一个级联序列，它将测试建议的[3+2]环加成反应，作为我们合成的最后一步，并将探索其与另一种塞库涅加生物碱，氟尿苷A的关系。

Our research program is a blend of fundamental and applied research in organic chemistry. The fundamental research focuses on the development of novel synthetic methods and the total synthesis of natural products. The applied portion of our research program is focused on the design and development of novel hybrid molecules for cancer treatment. In the fundamental research described in this proposal, we will pursue the synthesis of two natural products, palau'amine and virosaine. Palau'amine, a marine alkaloid with potent immunosuppresant activity, is a highly challenging target for chemical synthesis due to its density of functional groups and challenging stereochemistry. We are developing a Diels-Alder strategy to set the central carbocyclic ring and a conjugate addition/oxidative double-closure to close the trans-fused pyrrole amide/guanidine acetal portion of the molecule. Virosaine is a newly isolated Securinega alkaloid that is one of only a few molecules that has been proposed to arise biosyntheticallly by a [3+2] nitrone cycloaddition. We are developing a cascade sequence which will test the proposed [3+2] cycloaddition as the final step of our synthesis and will probe its relation to another Securinega alkaloid, flueggine A.