Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, 84602, USA.
Chem Rec. 2014 Aug;14(4):580-91. doi: 10.1002/tcr.201400005. Epub 2014 May 23.
The enantioselective total synthesis of (-)-acutumine is described. The synthetic strategy was inspired by the premise that the cyclohexenone ring could be derived from an aromatic precursor. After successful construction of a propellane model system, an initial attempt to prepare the spirocyclic subunit was thwarted by incorrect regioselectivity in a radical cyclization. A second-generation approach involving a radical-polar crossover reaction was successful, and the chemistry developed in the aforementioned model system was then applied to synthesize the natural product. Key reactions included a phenolic oxidation, a diastereoselective ketone allylation utilizing Nakamura's chiral allylzinc reagent, an anionic oxy-Cope rearrangement, an acid-promoted cyclization of a secondary amine onto an α,β-unsaturated ketal, and a regioselective methyl enol etherification of a 1,3-diketone.
描述了（-）-尖叶乌头堿的对映选择性全合成。该合成策略的灵感来自于这样一个前提，即环己烯酮环可以从芳香族前体衍生而来。在成功构建了推进剂模型系统后，由于自由基环化中不正确的区域选择性，最初尝试制备螺环亚基的尝试失败了。第二代方法涉及自由基-极性交叉反应是成功的，并且在前述模型系统中开发的化学被应用于合成天然产物。关键反应包括酚氧化、利用 Nakamura 的手性烯丙基锌试剂进行非对映选择性酮烯丙基化、阴离子氧-Cope 重排、在α，β-不饱和缩酮上进行仲胺的酸促进环化以及 1,3-二酮的区域选择性甲氧基乙醚化。
