Total Synthesis of the Terpenoid Phthalazinone Azamerone

萜类化合物二氮嗪酮Azamerone的全合成

• 批准号: 132935049
• 负责人: Professorin Dr. Tanja Gulder
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/132935049?language=en
• 关键词: Total; Synthesis; Terpenoid; Phthalazinone; Azamerone

The presented strategy provides a convergent, efficient, and short (19 overall steps) synthetic pathway to the unprecedented terpenoid phthalazinone azamerone (1). The preparation of 1 comprises three key steps, which all pose rewarding synthetic challenges. The formation of the cyclohexyl fragment 6 is achieved using a tandem deprotection/cyclization sequence. The chemoselective alignment of the synthetic steps towards 6 avoids the use of an orthogonal protective group strategy and therefore drastically reduces the number of steps. Essential for the synthesis of enantiomerically pure azamerone (1) is furthermore the selective generation of the stereocenter at C5 by a chemo- and thus regioselective 1,2-addition of 6 to the quinone moiety of the phthalazindienone 5. In-situ formation of a bidentate chiral Lewis acid complex with 5 does not only account for the chemoselective activation of the carbonyl atom at C5, but also directs the diastereotoposdifferentiating attack of the nucleophile. This concept for the introduction of chirality also avoids a lengthy chiral auxiliary manipulation. Formation of the dihydropyran fragment by a 6-endo-tet cyclization finalizes the framework of the natural product 1. Altogether, the synthesis of the structurally intriguing azamerone (1) provides the opportunity for the development of new synthetic strategies and thus contributes to the extension of the repertoire of modern synthetic chemistry.

所提出的策略提供了一个收敛的，有效的，和短（19个总步骤）的合成途径，前所未有的萜类化合物酞嗪酮氮杂苯酮（1）。1的制备包括三个关键步骤，它们都提出了有益的合成挑战。环己基片段6的形成使用串联脱保护/环化序列实现。合成步骤朝向6的化学选择性排列避免了使用正交保护基团策略，因此大大减少了步骤的数量。此外，对映体纯的阿扎美酮（1）的合成所必需的是通过6与酞嗪二烯酮5的醌部分的化学选择性和因此区域选择性1，2-加成在C5处选择性地产生立体中心。与5原位形成双齿手性刘易斯酸配合物不仅可以解释C5上羰基原子的化学选择性活化，而且还可以指导亲核试剂的非对映异构体分化攻击。这种引入手性的概念也避免了冗长的手性辅助操作。通过6-endo-tet环化形成的二氢吡喃片段最终确定了天然产物1的框架。总之，结构上有趣的阿扎美酮（1）的合成为开发新的合成策略提供了机会，从而有助于扩展现代合成化学的全部内容。