以保護基促進的芳基化反應合成複雜芳烴結構及應用於對映選擇性合成landomycinone

Abstract

Landomycins是angucycline抗生素中主要的一個族群，其特色為具有一個四環苯並[a]蔥醌骨架及八號碳上的去氧寡醣鏈。Landomycin A就是其中一種抗生素，可從Streptomyces cyanogenus的代謝物分離出來。該抗生素具有明顯的抗癌活性，例如抑制人類肺癌細胞株(NCI-60)。因此開發出一個簡單並有效率的合成方法來合成landomycins的核心結構是相當具有吸引力的。 我們發展了一個合成多取代之四環苯並[a]蔥醌骨架的方法。其關鍵反應為分子內碳氫芳基化反應，可成功地在高立障的環境下形成芳基芳基鍵。同時藉由Dötz benzannulation 以及這個分子內芳基化反應成功地合成landomycinone 1。另外，我們完整的分析關於landomycinone 1的核磁共振光譜資料，並將所有氫，碳原子標記出來。

Landomycins constitute a large group of angucycline antibiotics featuring a tetracyclic benz[a]anthraquinone core that is decorated with a deoxyoligosaccharide fragment at C8 position. Such as landomycin A isolated from Streptomyces cyanogenus S136 demonstrates antitumor activities against NCI 60 human cancer cell line panel. Thus, a facile and general strategy is highly desired for the synthesis of landomycins and their core structures. We developed a strategy for the construction of tetracyclic highly substituted benz[a]anthraquinone core. The key of the synthesis is a novel CH intramolecular arylation strategy, which enables the aryl-aryl bond formation in a highly congested environment. Additionally, we succecssfully synthesized landomycinone through Dötz benzannulation and this CH intramolecular arylation. Extensive NMR characterization of landomycinone 1 was performed and a full set of assigned 1H, 13C were updated.