Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling.
Practical Synthesis and Antifungal Investigation of Drimane Meroterpenoids Enabled by Nickel-Catalyzed Decarboxylative Coupling.
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DOI：
10.1021/acs.jnatprod.3c00100
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发表时间：
2023-05
影响因子：
5.1
通讯作者：
Shengxin Sun;Xia Wang;R. Csuk;Shengkun Li
中科院分区：
文献类型：
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作者：
Shengxin Sun;Xia Wang;R. Csuk;Shengkun Li
由于其结构多样性和生物活性的变化，Drimane meroterpenoids在发现新的药物先导物方面引起了越来越多的关注，但由于缺乏有效的模块化制备路线，进一步开发受到显着阻碍。已经建立了镍催化的脱羧交叉偶联范例，以迅速获得一系列的补身烷部分萜类化合物。氧化还原活性的补身烷前体是一种工作台稳定的偶联伴侣，并且容易从廉价的原料香紫苏醇中获得。这种转化的特点是对具有挑战性的官能团（苯酚、醛、酯等）的耐受性。和温和的条件下使用低成本的镍催化体系。具有挑战性的补身烷部分萜类化合物作为用于后期官能化的可多样化的高级中间体的直接可扩展合成进一步突出了合成效用。该方法促进了抗真菌研究，并最终发现化合物C8和C3作为新的抗水稻立枯病菌的抗真菌先导化合物，其EC 50值分别为4.9和7.2 μM。
Drimane meroterpenoids have drawn increasing attention in the discovery of novel pharmaceutical leads owing to their structural diversity and bioactivity variation, but further development is significantly impeded by the lack of an efficient modular route of preparation. A nickel-catalyzed decarboxylative cross-coupling paradigm has been established to expeditiously access a constellation of drimane meroterpenoids. The redox-active drimane precursor is a bench-stable coupling partner and is easily available from the inexpensive feedstock sclareol. This transformation features the tolerance of challenging functional groups (phenol, aldehyde, ester, etc.) and mild conditions with a low-cost nickel catalytic system. The synthetic utility is further highlighted by the direct scalable synthesis of challenging drimane meroterpenoids as diversifiable advanced intermediates for late-stage functionalizations. This method facilitated antifungal investigations and culminated in the discovery of compounds C8 and C3 as new antifungal leads against Rhizoctonia solani, with EC50 values of 4.9 and 7.2 μM, respectively.