Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2010 Feb 24;132(7):2157-9. doi: 10.1021/ja9097252.
A total synthesis of phostriecin (2), previously known as sultriecin (1), its structural reassignment as a phosphate versus sulfate monoester, and the assignment of its relative and absolute stereochemistry are disclosed herein. Key elements of the work, which provided first the originally assigned sulfate monoester 1 and then the reassigned and renamed phosphate monoester 2, relied on diagnostic (1)H NMR spectroscopic properties of the natural product for the assignment of relative and absolute stereochemistry as well as the subsequent structural reassignment, and a convergent asymmetric total synthesis to provide the unequivocal authentic materials. Key steps of the synthetic approach include a Brown allylation for diastereoselective introduction of the C9 stereochemistry, an asymmetric CBS reduction to establish the lactone C5-stereochemistry, diastereoselective oxidative ring expansion of an alpha-hydroxyfuran to access the pyran lactone precursor, and single-step installation of the sensitive Z,Z,E-triene unit through a chelation-controlled cuprate addition with installation of the C11 stereochemistry. The approach allows ready access to analogues that can now be used to probe important structural features required for protein phosphatase 2A inhibition, the mechanism of action defined herein.
本文报道了磷丝菌素（2）的全合成，其先前被称为磺丝菌素（1），其结构被重新指定为磷酸单酯而非硫酸单酯，并且确定了其相对和绝对立体化学。这项工作的关键要素，首先提供了最初指定的硫酸单酯 1，然后重新指定并重新命名为磷酸单酯 2，依赖于天然产物的诊断（1）H NMR 光谱性质，用于确定相对和绝对立体化学以及随后的结构重新指定，以及收敛的不对称全合成，以提供明确的真实材料。合成方法的关键步骤包括布朗烯丙基化以非对映选择性引入 C9 立体化学，不对称 CBS 还原以建立内酯 C5 立体化学，通过α-羟基呋喃的非对映选择性氧化环扩张来获得吡喃内酯前体，以及通过螯合控制的铜配合物加成一步安装敏感的 Z,Z,E-三烯单元，并同时安装 C11 立体化学。该方法可轻松获得类似物，现在可用于研究蛋白质磷酸酶 2A 抑制所需的重要结构特征，本文定义了其作用机制。
