TOTAL SYNTHESIS OF MADANGAMINE A

新分离的生物碱马丹明A(1)是一个结构独特的化合物 越来越多的与生物遗传有关的天然产品的成员 从海绵中提取。Madangamine A已被证明具有活性 ED50‘S对几种不同类型癌细胞的作用 微克/毫升范围。顺式多烯官能化存在于1 似乎会抑制对其进行受控和系统的修改 结构通过降解的方法。此外，绝对的 配置%1尚未阐明。因此，一个 对映体控制的全合成1，它足够灵活，以允许 为了便于类似物的合成，提出了一种新的合成方法。建议的路线 首先是非对映选择性的Diels-Alder反应，然后是 碘内酯化生成环己烷环。三环核心 然后使用带有N-的烯胺环化反应组装1 酰亚胺离子。然后，每个较大的环将形成一个 使用系绳/环化策略的收敛方式 易于适应不同系绳长度的并入 功能性。因此，生产1的类似物以 研究其构效关系，提高其药用价值 价值将得到促进。

The recently isolated alkaloid madangamine A (1) is a structurally unique member of a growing class of biogenetically related natural products obtained from marine sponges. Madangamine A has been shown to be active against several different types of cancer cell lines with ED50's in the microgram/milliliter range. The cis polyene functionally present in 1 would appear to inhibit a controlled and systematic modification of its structure through degradative methods. Moreover, the absolute configuration 1 has not yet been elucidated. Consequently, an enantiocontrolled total synthesis of 1 which is flexible enough to allow for the facile synthesis of analogs is proposed. The proposed route begins with a diastereoselective Diels-Alder reaction followed by an iodolactonization to generate the cyclohexane ring. The tricyclic core of 1 will then be assembled using an enamine cyclization with an N- acyliminium ion. Each of the larger rings will then be formed in a convergent manner using a tether/cyclization strategy which will be easily amenable to the incorporation of different tether lengths and functionality. Consequently, the production of analogs of 1 in order to study its structure/activity relationships and improve its medicinal value will be facilitated.