Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
J Am Chem Soc. 2013 Nov 27;135(47):17990-8. doi: 10.1021/ja409944u. Epub 2013 Nov 18.
An asymmetric total synthesis of the aminocyclopentitol pactamycin is described. The title compound is delivered in 15 steps from 2,4-pentanedione. Critical to this approach was the exploitation of a complex symmetry-breaking reduction strategy to assemble the C1, C2, and C7 relative stereochemistry within the first four steps of the synthesis. Multiple iterations of this reduction strategy are described, and a thorough analysis of stereochemical outcomes is detailed. In the final case, an asymmetric Mannich reaction was developed to install a protected amine directly at the C2 position. Symmetry-breaking reduction of this material gave way to a remarkable series of stereochemical outcomes leading to the title compound without recourse to nonstrategic downstream manipulations. This synthesis is immediately accommodating to the preparation of structural analogs.
本文描述了氨基环戊醇巴替霉素的不对称全合成。标题化合物可通过 2,4-戊二酮经 15 步反应制得。该方法的关键在于利用复杂的对称破缺还原策略，在合成的前四个步骤中组装 C1、C2 和 C7 的相对立体化学。本文描述了多次迭代的这种还原策略，并详细分析了立体化学结果。在最后一种情况下，开发了不对称 Mannich 反应，可直接在 C2 位置引入保护胺。对该材料进行的对称破缺还原导致了一系列显著的立体化学结果，从而得到标题化合物，而无需进行非策略性的下游操作。该合成方法可直接用于制备结构类似物。
