Pfaffinger Dana E, Krische Michael J
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
Org Lett. 2025 May 2;27(17):4501-4506. doi: 10.1021/acs.orglett.5c01026. Epub 2025 Apr 10.
A formal synthesis of fostriecin via convergent assembly of two fragments prepared via asymmetric alcohol-mediated C-C coupling is described. One fragment is made by the enantioselective iridium-catalyzed allylation of an allylic alcohol mediated by allyl acetate. The other fragment is made via enantioselective ruthenium-catalyzed reductive -(α-alkoxy)allylation of an aldehyde mediated by an alkoxyallene (where 2-propanol is the hydrogen source), representing the first use of this method in target-oriented synthesis. Metathetic fragment union enables interception of a late-stage compound that previously required a 25 step (LLS) synthesis in only 7 steps (LLS).
本文描述了通过不对称醇介导的碳-碳偶联制备的两个片段的汇聚组装来实现磷霉素的形式合成。一个片段是通过乙酸烯丙酯介导的对映选择性铱催化的烯丙醇烯丙基化反应制备的。另一个片段是通过烷氧基丙二烯介导的醛的对映选择性钌催化的还原-(α-烷氧基)烯丙基化反应制备的（其中2-丙醇为氢源），这代表了该方法在目标导向合成中的首次应用。复分解片段结合能够截获一种后期化合物，该化合物以前需要25步（线性最长步骤数）合成，现在仅需7步（线性最长步骤数）即可完成。
