Strand Daniel, Norrby Per-Ola, Rein Tobias
KTH Chemical Science and Engineering, Organic Chemistry, SE-100 44 Stockholm, Sweden.
J Org Chem. 2006 Mar 3;71(5):1879-91. doi: 10.1021/jo052233k.
Syntheses of the nonclassical annonaceous acetogenins, pyranicin, and pyragonicin from common late-stage intermediates are presented. The construction of key elements relies on asymmetric HWE reactions, including the desymmetrization of a meso-dialdehyde and a parallel kinetic resolution of a racemic aldehyde. A stereoconvergent Pd-catalyzed substitution serves to install the C4 stereocenter in protected form with different orthogonal protective groups. A divergent strategy to form 1,4- and 1,6-diols, employing stereoselective Zn-mediated alkynylations, is used for completion of the core structures. Notably, the stereoselective coupling reaction toward pyragonicin proceeds with highly functionalized fragments. The methodology is further expanded by a divergent synthesis of all stereoisomers of the 2,3,6-trisubstituted tetrahydropyran subunit.
本文介绍了从常见的后期中间体合成非经典番荔枝内酯、吡喃霉素和吡拉戈霉素的方法。关键结构单元的构建依赖于不对称Horner-Wadsworth-Emmons（HWE）反应，包括内消旋二醛的去对称化和外消旋醛的平行动力学拆分。立体汇聚的钯催化取代反应用于以不同的正交保护基形式安装受保护的C4立体中心。采用立体选择性锌介导的炔基化反应形成1,4-二醇和1,6-二醇的发散策略用于完成核心结构的构建。值得注意的是，吡拉戈霉素的立体选择性偶联反应是通过高度官能化的片段进行的。通过2,3,6-三取代四氢吡喃亚基的所有立体异构体的发散合成，该方法得到了进一步扩展。
