Normandie Université, UNIROUEN, INSA de Rouen, CNRS, Laboratoire COBRA (UMR 6014 & FR 3038), 76000 Rouen, France.
Org Biomol Chem. 2019 Apr 10;17(15):3819-3824. doi: 10.1039/c9ob00547a.
The total synthesis of spiromastilactone A is reported for the first time. A swift strategy is presented that involves a pivotal enantioselective nucleophilic 1,2-alkylation of an aldehyde prepared in four quantitative synthetic steps from commercial 2,4-dihydroxybenzoic acid. This key reaction, which was described very recently by our group and carried out here on a gram scale, involves cheap and easily accessible tricoordinated chiral lithium amido zincates. The resulting enantioenriched secondary alcohol is involved afterward in an efficient intramolecular cyclization providing the phthalide core of the target, and two quantitative additional steps aiming to deprotect the phenol groups then introduce chlorine atoms end the synthetic scheme. Spiromastilactone A is obtained in 44% overall yield in eight synthetic steps, among which six are quantitative, and the 89 : 11 enantiomeric ratio (78% ee value) is in favor of the right enantiomer (R configuration).
首次报道了螺旋马斯特酮 A 的全合成。本文提出了一种快速策略，涉及醛的对映选择性亲核 1,2-烷基化反应，该醛可以通过商业 2,4-二羟基苯甲酸经四个定量合成步骤制备。这个关键反应是我们小组最近描述的，并且在这里进行了克级规模的实验，涉及到廉价且易于获得的三配位手性锂酰胺锌盐。随后，得到的手性富集仲醇参与了高效的分子内环化反应，提供了目标物的邻苯二甲酸内酯核心，随后进行了两个定量的额外步骤，旨在脱保护酚基团并引入氯原子，从而完成了合成方案。在八步合成中，以 44%的总收率获得了螺旋马斯特酮 A，其中六个步骤是定量的，89:11 的对映体比例（78%ee 值）有利于右对映体（R 构型）。
