Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, PR China.
State Key Laboratory of Bioorganic and Natural Products Chemistry, 345 Lingling Road, Shanghai 200032, PR China.
J Org Chem. 2021 Aug 20;86(16):11053-11071. doi: 10.1021/acs.joc.0c02667. Epub 2021 Jan 13.
This article describes the full details of our synthetic efforts toward the enantioselective total synthesis of the complex alkaloid methoxystemofoline. The enantioselective construction of the tetracyclic core features: (1) the Keck allylation at the -α bridgehead carbon to forge the tetrasubstituted stereocenter; (2) an olefin cross-metathesis reaction for the side-chain elongation that is amenable for the synthesis of congeners and analogues; and (3) a regioselective aldol addition reaction with methyl pyruvate that ensured the subsequent regioselective cyclization reaction to construct the fourth ring. Overman's method was employed to install the 5-(alkoxyalky1idene)-3-methyl-tetronate moiety. In the last step, a nonstereoselective reaction resulted in the formation of both the proposed structure of methoxystemofoline and its -stereoisomer, the natural product (revised structure), in a 1:1 ratio. We suggest to rename the natural product as isomethoxystemofoline, and report for the first time the complete H NMR data for this natural product.
本文详细描述了我们对复杂生物碱甲氧基体系啉进行对映选择性全合成的合成努力。四环核心的对映选择性构建具有以下特点：（1）在-α桥头碳原子上进行 Keck 烯丙基化，以形成四取代的立体中心；（2）通过烯烃交叉复分解反应进行侧链延长，适用于同系物和类似物的合成；（3）与丙酮酸甲酯进行区域选择性羟醛加成反应，确保随后的区域选择性环化反应构建第四个环。采用 Overman 方法安装 5-(烷氧基烷基亚基）-3-甲基-四氢呋喃酯部分。在最后一步，非立体选择性反应导致形成甲氧基体系啉的提议结构及其 -对映异构体，天然产物（修订结构）以 1:1 的比例形成。我们建议将天然产物重新命名为异甲氧基体系啉，并首次报道该天然产物的完整 H NMR 数据。
