Structural Elucidation and Total Synthesis of Three 9-Norlignans from Curculigo capitulata

Abstract

Capitulactones A–C, three unprecedented 9-norlignans featuring a unique 3,5-dihydrofuro­[2,3-d]­oxepin-7­(2H)-one scaffold, were isolated from the roots of Curculigo capitulata. Their structures with absolute configurations were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Biomimetic total syntheses of three pairs of the corresponding enantiomers were achieved in 9–10 steps with overall yields of 14.8, 12.7, and 10.3%, respectively. Notably, the unique scaffold of the common western hemisphere of the molecules was constructed by using the oxidation–reduction strategy from benzodihydrofuran.

Discovery of four modified classes of triterpenoids delineated a metabolic cascade: compound characterization and biomimetic synthesis

“…1,2 Cascade reactions based on biosynthetic mechanism have been recognized as a crucial synthetic strategy enabling consecutive chemical transformations. [3][4][5][6][7] In addition to discovering structurally interesting and biologically significant natural molecules, [8][9][10][11][12][13][14][15] we have been committed to the biomimetic and/or bioinspired syntheses of important natural compounds identified by our research group as well, which aimed to validate the proposed biosynthetic pathways from chemical view. [16][17][18][19] Dichapetalin-type triterpenoids, a rare category of natural products featuring the modified skeletons by condensing a C6-C2 unit to the A ring of 13,30-cycodammarane triterpenoids, were found as the characteristic components of Dichapetalum and Phyllanthus genera.…”

Total Synthesis of Capitulactone: Analysis of Problem 9 of the 54th International Chemistry Olympiad

“…大叶仙茅(Curculigo capitulata)是一种生长在中国南方地区的植物，作为传统的中草药用于治疗 多种疾病。仙茅内酯(Capitulactone，1)是从大叶仙茅的根中分离提取到天然产物，其结构和绝对构型 是通过波谱分析并结合全合成来确定的。 如下图所示，化合物1的全合成起始于4-溴黎芦醚(2)的碘代反应，经过了关键合成中间体12。 [3,4] 。这道题 所涉及到的合成方法学就是以D-甘露醇为手性源，合成(R)-氯代环氧丙烷(7)，进而合成天然产物1的 实际应用案例 [5] 。 9-2小题涉及到的知识点是缩酮的形成。这是一个经典有机反应，在合成化学中常用于邻二醇或 者醛酮的保护。这个反应需要在质子酸或Lewis酸催化下进行，且反应是可逆的，反应产生的副产物 为水，所以通常需要在脱水条件下进行 [5] 。因此，9-2小题的正确选项为(d)，即无水ZnCl 2 。 从化合物14到15转化的反应类型属于邻二醇的氧化断裂，经典的氧化剂包括高碘酸和四醋酸铅 等，文献中这两种氧化剂都能够实现从14到15的转化 [3][4][5] 。巧妙的是，化合物14氧化断裂之后产生的 两个片段完全相同(包括绝对构型)，即化合物15。从15到16的转化属于醛的还原，硼氢化钠是常用的 还原剂。 从17到18的转化属于环状缩酮的水解反应，在酸催化下进行，这是常用的环状缩酮保护策略中 的脱保护方法。从18到19的转化属于分子内亲核取代反应(S N 2机理)，形成环氧化合物19。在这一反 应中手性碳的构型保持不变。 9-3小题的正确答案，即化合物15、16、18和19的结构式如上图所示。 需要指出的是，由中间体17亦可制备S构型的氯代环氧丙烷 [5] ，路线如下： 实际上，岳建民院士正是利用R和S构型的氯代环氧丙烷，分别合成得到了天然的仙茅内酯A、 B、C和它们的对映体，从而最终确定了这些天然产物的绝对构型 [1] 。 9-4小题中涉及的模型反应为乙二醇(22)与2-甲氧基丙烯(23)在酸催化下生成缩酮(24) [6] 。该反应 虽然属于经典有机反应，但2-甲氧基丙烯这种试剂并不常用，故题目中给出了反应过程中经历的主 要中间体，仅让学生排序，从而降低了题目的难度。这个反应的机理如下所示，故9-4小题的正确选 项是(b)。…”

Phytochemistry and Pharmacological Activity of Plants of Genus Curculigo: An Updated Review Since 2013

“…Their structures with the absolute configurations were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. The unique scaffold of the common western hemisphere of the molecules was constructed by using the oxidation-reduction strategy from benzodihydrofuran ( Figure 2 ) [ 39 ]. In addition, hypothetical biosynthetic pathways for capitulactones A–C ( 4 – 6 ) were also proposed ( Scheme 1 ).…”