Department of Chemistry, University of California, Berkeley, California 94720, United States.
J Am Chem Soc. 2021 Mar 31;143(12):4732-4740. doi: 10.1021/jacs.1c00457. Epub 2021 Mar 17.
Nitrogen heterocycles (azacycles) are common structural motifs in numerous pharmaceuticals, agrochemicals, and natural products. Many powerful methods have been developed and continue to be advanced for the selective installation and modification of nitrogen heterocycles through C-H functionalization and C-C cleavage approaches, revealing new strategies for the synthesis of targets containing these structural entities. Here, we report the first total syntheses of the lycodine-type alkaloids casuarinine H, lycoplatyrine B, lycoplatyrine A, and lycopladine F as well as the total synthesis of 8,15-dihydrohuperzine A through bioinspired late-stage diversification of a readily accessible common precursor, -desmethyl-β-obscurine. Key steps in the syntheses include oxidative C-C bond cleavage of a piperidine ring in the core structure of the obscurine intermediate and site-selective C-H borylation of a pyridine nucleus to enable cross-coupling reactions.
氮杂环（氮杂环）是许多药物、农用化学品和天然产物中常见的结构基序。已经开发出许多强大的方法，并继续通过 C-H 功能化和 C-C 断裂方法来推进氮杂环的选择性安装和修饰，为含有这些结构实体的目标的合成揭示了新的策略。在这里，我们报告了 lycodine 型生物碱 casuarinine H、lycoplatyrine B、lycoplatyrine A 和 lycopladine F 的首次全合成，以及通过易获得的通用前体 -desmethyl-β-obscurine 的生物启发的后期多样化来实现 8,15-二氢海帕碱的全合成。合成中的关键步骤包括在 obscurine 中间体的核心结构中环化 C-C 键的氧化断裂，以及吡啶核的位点选择性 C-H 硼化以实现交叉偶联反应。
