Development of a sustainable reaction sequence for the synthesis of 9,11-secosterols and its application in the synthesis of aplysiasecosterols and pinnigorgiols using a terminated (vinylogous) ketol rearrangement cascade

即使是简单的9，11-Secosterol的合成也经常依赖于有毒重金属的使用，即汞、臭氧和铅，通常超过化学计量比的量。在过去的两年中，分离出了富含氧的三环[5，2，1，1]正十二烷类化合物。作为生物合成假说，提出了9，11-Secosterol的(Venylogous)酮醇级联重排反应。从生物学上讲，羽片甾醇和羽片甾醇及其可能的生物合成前体羽片甾醇具有几种有趣的生物活性。例如，Aplysiasecosterol是某些人髓系白血病细胞系的选择性抑制剂，因此，该项目的目的是建立一种可持续的、普遍的获得9，11-Secosterol的途径，而不依赖于重金属的使用。这个项目的前期工作已经导致了一个例子，在这个例子中，这一先决条件已经实现。在这些结果的基础上，接下来我们将把我们发表的关于甾醇(一种14，15-倍半甾醇)的合成工作应用于9，11-倍半甾醇的合成，并同时使用这两种方法，a-氯-伽马-羟基-三角洲-酮烯酮的阴离子重排以及从5，8-甾二烯合成偏内过氧物。有了9，11-第二甾醇的路线，我们将尝试实现(乙烯)酮醇重排级联反应。这也将为这些天然产物的生物合成原理提供一些线索。最终，将对从相应的羽扇豆醇和马鞭草甾醇中提取的预期天然产物进行研究。

The synthesis of even simple 9,11-secosterols frequently relies on the use of toxic heavy metals, i.e. mercury, osmium, and lead, typically in greater than stoichiometric quantities. In the last two years, the aplysiasecosterols and pinnigorgiols (oxygen-rich tricyclo[5,2,1,1]decanes) were isolated. As a biosynthetic hypothesis, a cascade of (vinylogous) ketol rearrangements of 9,11-secosterols was proposed. Biologically, the aplysiasecosterols and pinnigorgiols, as well as their possible biosynthetic precursors, the pinnisterols, possess several interesting bioactivities. Aplysiasecosterol, for example, is a selective inhibitor of certain human myelogenous leukemia cell lines.The aim of this project is thus, to establish a sustainable, and general access to 9,11-secosterols, that does not rely on the use heavy metals. Preliminary work for this project has already led to one example where this prerequisite ilphas fulfilled. Building upon these results, we will next apply our published work on the synthesis of strophasterol (a 14,15-secosterol) to the synthesis of 9,11-secosterols and use both, the anionic rearrangement of a-chloro-gamma-hydroxy-delta-keto-enones as well as the synthesis of meta-endoperoxide peroxides from 5,8-steroidal dienes. With a route to 9,11-secosterols in hands, the realization of the (vinylogous) ketol rearrangement cascade will then be attempted. This will also shed some light on the biosynthetic rationale of these natural products. Eventually, studies in the anticipated natural products from the corresponding pinnisterols and irciniasecosterols will be conducted.