The Total Synthesis of Chalcitrin

The first total synthesis of the yellow pigment chalcitrin, a structurally distinct pulvinic acid dimer obtained from Chalciporous piperatus, has been achieved in 17 linear steps from commercially available materials. Key elements of the design include the use of a Au­(I)-catalyzed Conia ene reaction and an N-heterocyclic carbene-mediated acyloin addition to rapidly fashion its unique polycyclic core, with the two high oxidation state side chains introduced in a single step via a late-stage double Stille coupling. Of note, many alternate designs based on differential final couplings failed, likely because of the hindered nature of the core. In addition, significant challenges in final natural product characterization in terms of matching NMR spectra were experienced; our studies reveal that the originally characterized material was its carboxylate salt form not its free acid.从市售原料出发，经17步线性反应，首次完成了黄色色素查尔西菌素（chalcitrin）的全合成；该化合物为从Chalciporous piperatus中分离得到的结构独特的枕形酸二聚体（pulvinic acid dimer）。该合成路线的关键设计策略包括采用一价金（Au(I)）催化的科尼亚烯（Conia ene）反应与氮杂环卡宾（N-heterocyclic carbene）介导的偶姻加成反应，以快速构建其独特的多环核心，并通过后期双斯蒂勒（Stille）偶联反应一步引入两条高氧化态侧链。值得注意的是，诸多基于差异化后期偶联策略的替代合成方案均告失败，这大概率源于该分子核心的显著位阻效应。此外，在最终天然产物的表征环节，我们在匹配核磁共振（NMR）谱图方面遭遇了重大挑战；研究结果显示，最初被表征的样品实为其羧酸盐形式，而非游离酸形态。