Trost Barry M, O'Boyle Brendan M
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
J Am Chem Soc. 2008 Dec 3;130(48):16190-2. doi: 10.1021/ja807127s.
In spite of the tremendous advances in modern spectroscopic methods, organic synthesis continues to play a pivotal role in elucidating the full structures of complex natural products. This method has the advantage that, even in the absence of a firm structural assignment, a combination of logic and spectroscopic comparison can arrive at the correct structure. Herein, we report execution of this strategy with respect to ushikulide A, a newly isolated and previously stereochemically undefined member of the oligomycin-rutamycin family. To maximize synthetic efficiency, we envisioned chemoselective manipulation of orthogonally reactive functional groups, notably alkenes and alkynes as surrogates for certain carbonyl and hydroxyl functionalities. This approach has the dual effect of minimizing the number of steps and protecting groups required for our synthetic route. This strategy culminated in the efficient synthesis and stereochemical assignment of ushikulide A.
尽管现代光谱方法取得了巨大进展，但有机合成在阐明复杂天然产物的完整结构方面仍然发挥着关键作用。这种方法的优点是，即使在没有确定的结构归属的情况下，逻辑推理和光谱比较相结合也能得出正确的结构。在此，我们报告了针对ushikulide A执行该策略的情况，ushikulide A是寡霉素-鲁他霉素家族新分离出的、之前立体化学未明确的成员。为了最大限度地提高合成效率，我们设想对正交反应性官能团进行化学选择性操作，特别是将烯烃和炔烃作为某些羰基和羟基官能团的替代物。这种方法具有双重效果，即最大限度地减少我们合成路线所需的步骤数和保护基团。该策略最终实现了ushikulide A的高效合成和立体化学归属。
