Department of Chemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458, USA.
J Am Chem Soc. 2012 Sep 19;134(37):15237-40. doi: 10.1021/ja306362m. Epub 2012 Sep 7.
An asymmetric synthesis of alkaloid (-)-205B, a tricyclic member of the architecturally diverse family of natural products isolated from the skin of neotropical poison frogs, is described that proceeds through two recently developed stereoselective synthetic methods: (1) Ti-mediated allylic alcohol-imine reductive cross-coupling and (2) intramolecular [3+2] cycloaddition of a glyoxylate-based homoallylic nitrone. The utility of this latter cycloaddition process for the assembly of the stereochemically dense piperidine core of 205B is noteworthy, as this method enables direct [3+2] cycloaddition of an intermediate homoallylic (E)-nitrone via a pathway that is stereochemically unscathed by competitive [3,3]-sigmatropic rearrangement processes. Overall, the synthesis is asymmetric, concise, and highly stereoselective-features which point to the potential future utility of these chemical methods in natural product synthesis and medicinal chemistry.
不对称合成生物碱 (-)-205B，一种结构多样的天然产物家族的三环成员，从新热带毒蛙的皮肤中分离出来，描述了通过两种最近开发的立体选择性合成方法：（1）Ti 介导的烯丙醇-亚胺还原交叉偶联和（2）基于糖醛酸的偕亚丙基硝酮的分子内 [3+2] 环加成。后一种环加成过程对于 205B 的立体化学密集哌啶核心的组装是值得注意的，因为该方法通过一种途径允许中间体偕亚丙基（E）-硝酮的直接 [3+2] 环加成，该途径不受竞争 [3,3]-σ重排过程的立体化学影响。总的来说，该合成具有不对称性、简洁性和高度的立体选择性，这些特点表明这些化学方法在天然产物合成和药物化学中有潜在的未来应用。
