Synthesis and Structure Elucidation of Tedanolide C

本项目的目标是全合成tedanolide C。与其他tedanolide相比，tedanolid C表现出更高的氧化模式，导致伯醇旁边的叔羟基。这些特征代表了构建这一片段的特殊合成挑战，也代表了所有构建块的组装。我们开发了Kiyooka Aldol反应的一个变体，我们用它来产生这个复杂的片段。在这份提案中，我们描述了如何使用我们的Kiyooka Aldol方法来构建tedanolide C。全合成tedanolide C将具有重要意义，因为有几个基团对所提议的构型提出质疑，而成功的全合成将确认其中一个结构建议。Tedanolide C以及整个家族代表了一类重要的天然产物，因为它们定位于核糖体上不同的结合部位，属于最具细胞毒性的天然产物之一。事实上，这些都是海洋天然产物，无法通过发酵获取，使合成获取变得更加重要。

This projects aims at the total synthesis of tedanolide C. Tedanolid C exhibits, compared to the other tedanolides, a much higher oxidation pattern which leads to a tertiary hydroxyl group next to a primary alcohol. These features represent a particular synthetic challenge for the construction of this very fragment but also for the assembly of all building blocks. We developed a variation of the Kiyooka aldol reaction, which was used by us for the generation of this complex fragment. Within this proposal we delineate how tedanolide C can be constructed using our Kiyooka aldol approach. A total synthesis of tedanolide C would have significance since several groups question the proposed configuration and a successful total synthesis would confirm one or the other structural proposal. Tedanolide C as well as the whole family of tedanolides represent an important class of natural products as they address to distinct binding sites at the ribosome and belong to one of the most cytotoxic natural products. The fact that these are marine natural products disables access through fermentation and makes a synthetic access even more important.