Total Synthesis of the Terpenoid Phthalazinone Azamerone

所提出的策略提供了一条收敛、高效和短(总共19步)的合成路线来合成史无前例的萜类二氮杂氮酮(1)。1的制备包括三个关键步骤，这三个步骤都构成了有益的合成挑战。使用串联的去保护/环化序列实现环己基片段6的形成。合成步骤向6的化学选择性对齐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。合成对映体纯的氮丙酮(1)的关键是通过化学方法选择性地生成C5的立体中心，从而使6的区域选择性加成到联苯二酮5的部分上。与5原位形成双齿手性Lewis酸络合物不仅解释了C5上的羰基原子的化学选择性活化，而且还指导了亲核试剂的非对映异构体的攻击。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-内位环化形成二氢吡喃片段，最终确定了天然产物1的骨架。总之，结构有趣的氮丙酮(1)的合成为开发新的合成策略提供了机会，从而有助于现代合成化学的研究范围的扩大。

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.