Synthetic Studies of the Marine Alkaloids, Madangamines with Anti Tumor Activities

Madangamine A是一种五环生物碱，由Andersen于1994年从海绵Xestospongia ingens中分离得到。不久之后，这种生物碱类型的新成分，madangamines B-E，从同一生物中分离出来。Madangamine A对P388、A549、U373和MCF-7肿瘤细胞系具有细胞毒活性。在这个研究项目中，我完成了芒果胺的ABC和ace环框架的构建。酮-氨基酚的N， o-乙酰化可以快速构建以C4为中心的2-氮杂环[3.3.1]壬烷骨架。这一策略使得马来胺类生物碱的中心重杂环核心（abc环）的立体选择性构建成为可能。在我们研究的下一阶段，我们通过环己酮衍生物的N， o -乙酰化反应、保持几何形状的交叉偶联反应和分子内还原胺化反应构建了2-氮杂环[3.3.1]壬烷骨架，有效地构建了madangamine三环，4-氮杂环[11.2.2.0^<4.14>]十六烷基12-烯，包括一个11元的大环（ace环）。根据以上结果，我未来的研究将集中在构建一个15元的大环（d环），用于全合成芒果胺。

Madangamine A is a pentacyclic alkaloids that was isolated from the marine sponge Xestospongia ingens by Andersen in 1994. Soon after, new constituents of this alkaloid type, madangamines B-E, were isolated from the same organism. Madangamine A exhibits cytotoxic activities against P388, A549, U373, and MCF-7 tumor cell lines. In this research project, I have accomplished the construction of the ABC and ACE-ring frameworks of madangamines. N, O-Acetalization of the keto-aminophenol allows rapid construction of the 2-azabicyclo[3.3.1]nonane skeleton with a quaternary carbon center at C4. This strategy enabled the stereoselective construction of the central diazatricyclic core (ABC-ring) of the madangamine alkaloids. In the next stage of our investigation, an efficient construction of the madangamine tricyclic ring, 4-azatricyclo[11.2.2.0^<4.14>]heptadec-12-ene, including an 11-membered macrocycle (ACE-ring) has been accomplished via construction of the 2-azabicyclo[3.3.1]nonane skeleton by N, O-acetalization of a cyclohexanone derivative, geometry-retained cross-coupling reaction, and intramolecular reductive amination. From the results obtained above, my future studies will be focused on the construction of a 15-membered macrocycle (D-ring) for the total synthesis of madangamines.