Merging Chemo- and Biocatalysis to Facilitate the Syntheses of Complex Natural Products: Enantioselective Construction of an N-Bridged [3.3.1] Ring System in Indole Terpenoids
Merging Chemo- and Biocatalysis to Facilitate the Syntheses of Complex Natural Products: Enantioselective Construction of an N-Bridged [3.3.1] Ring System in Indole Terpenoids
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DOI：
10.1021/acscatal.2c04076
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发表时间：
2022-11
期刊：
影响因子：
12.9
通讯作者：
Yoshinori Hashimoto;Shingo Harada;Ryosuke Kato;Kotaro Ikeda;Jannis Nonnhoff;H. Gröger;T. Nemoto
中科院分区：
文献类型：
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作者：
Yoshinori Hashimoto;Shingo Harada;Ryosuke Kato;Kotaro Ikeda;Jannis Nonnhoff;H. Gröger;T. Nemoto
虽然吲哚稠合氮杂双环[3.3.1]壬烷的分子结构基序在具有生物学意义的天然产物中很常见，但其催化不对称合成仍有待探索。在此，我们报告了一种催化方法的正式合成超过20种类型的sarpagine/macroline生物碱。两个关键步骤是使用基于廉价铜的金属-卡宾物种的酰胺插入反应和生物催化的不对称去对称化，产生所需的手性N-桥接[3.3.1]支架。当使用来自Candida rugosa的脂肪酶时，酶促步骤进行高度对映选择性，这被证明是最好的对称性破坏。后期引入的吲哚单元的功能，然后建立了一个多样性导向的合成途径走向吲哚萜类变体。
Although the molecular structural motif of indole-fused azabicyclo[3.3.1]nonane is common in biologically significant natural products, its catalytic asymmetric synthesis remains underexplored. Herein, we report a catalytic approach for the formal synthesis of more than 20 types of sarpagine/macroline alkaloids. Two key steps are the amide insertion reaction using a metal-carbene species based on cheap copper and biocatalytic asymmetric desymmetrization, producing the desired chiralN-bridged [3.3.1] scaffold. The enzymatic step proceeds highly enantioselectively when using lipase fromCandida rugosa, which turned out to be the best for breaking the symmetry. Late-stage introduction of an indole unit with functionalities then established a diversity-oriented synthetic pathway toward indole terpenoid variants.