Studies in Natural Product Synthesis and Catalysis of Pericyclic Reactions

我们的研究项目是有机化学的基础研究和应用研究的结合。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。我们的研究项目的应用部分集中在设计和开发用于癌症治疗的新型杂交分子。在本提案所描述的基础研究中，我们将追求两种天然产物的合成，帕劳胺和病毒碱。帕劳胺是一种具有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性质，它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，以设置中心碳环和共轭加成/氧化双闭合来关闭分子的交叉融合吡咯酰胺/胍缩醛部分。病毒碱是一种新分离的Securinega生物碱，是少数被提出通过[3+2]硝基环加成产生的分子之一。我们正在开发一个级联序列，将测试所提出的[3+2]环加成作为我们合成的最后一步，并将探索其与另一种Securinega生物碱的关系。

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.