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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

开发用于合成 9,11-棕榈甾醇的可持续反应序列及其在使用终止（乙烯同源）酮醇重排级联合成海兔甾醇和 Pinnigorgiols 中的应用

基本信息

批准号：
396114738
负责人：
Professor Dr. Philipp Heretsch
金额：
--
依托单位：
Institut für Organische Chemie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/396114738?language=en
关键词：
Development sustainable reaction sequence synthesis

项目摘要

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.

即使是简单的9，11-开环甾醇的合成也经常依赖于使用有毒重金属，即汞、锇和铅，通常大于化学计量的量。在过去的两年中，分离出了阿托西阿托西阿作为一种生物合成假说，提出了一个级联的（乙烯基）酮重排的9，11-开环甾醇。在生物学上，紫茎泽兰和羽叶珊瑚醇，以及它们可能的生物合成前体，羽叶甾醇，具有几个有趣的生物活性。例如，紫茎泽兰甾醇是某些人类骨髓性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个可持续的，普遍获得9，11-开环甾醇，不依赖于使用重金属。这个项目的初步工作已经导致一个例子，这一先决条件ilph已经实现。在这些结果的基础上，我们接下来将把我们发表的关于合成毒毛旋甾醇（14，15-开环甾醇）的工作应用于合成9，11-开环甾醇，并使用α-氯-γ-羟基-δ-酮-烯酮的阴离子重排以及从5，8-甾体二烯合成间-内过氧化物过氧化物。随着9，11-开环甾醇的路线在手，（乙烯基）酮醇重排级联的实现，然后将尝试。这也将揭示这些天然产物的生物合成原理。最后，将对相应的pinnisterols和irciniasecosteolites的预期天然产物进行研究。