Expediently Scalable Synthesis and Antifungal Exploration of (+)-Yahazunol and Related Meroterpenoids.
Expediently Scalable Synthesis and Antifungal Exploration of (+)-Yahazunol and Related Meroterpenoids.
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DOI：
10.1021/acs.jnatprod.8b00310
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发表时间：
2018-09
影响因子：
5.1
通讯作者：
Shasha Zhang;Xia Wang;Jin Hao;Dangdang Li;R. Csuk;Shengkun Li
中科院分区：
文献类型：
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作者：
Shasha Zhang;Xia Wang;Jin Hao;Dangdang Li;R. Csuk;Shengkun Li
介绍了（+）-野哈醇及其相关天然产物的高效合成和抗真菌活性的研究。该策略的核心是巴顿脱羧偶联，包括一锅自由基脱羧和醌加成级联。以市售廉价的（-）-香紫苏醇为原料，以五个最长线性序列（LLS）完成了（+）-雅哈醇的可放大合成。通过方便地制备（-）-zonarone、（-）-isozonarone、（-）-zonarol、（-）-isozonarol、（+）-chrozonarol和（+）-yahazunone证明了（+）-yahazunol的发散翻译潜力。这种方法也使得能够正式合成Puupehenol，Puupehedione和hongoquercin A。进行了抗真菌评价，这代表了（+）-yahazunone、（+）-8-O-乙酰基yahazunone和（+）-8-O-乙酰基yahazunol的第一个生物学特征。（+）-色唑萘酚和（+）-弥唑酮是有希望的抗核盘菌的候选物，其EC 50值分别为24.1和28.7 μM，证明优于原始模型（DM）和合成的杂环模拟物（3a）。这将有利于在不同植物病害的管理中建立化学库。
The efficient synthesis and antifungal exploration of (+)-yahazunol and related natural products are described. Central to this strategy is the Barton decarboxylative coupling, comprising a one-pot radical decarboxylation and quinone addition cascade. The scalable synthesis of (+)-yahazunol was accomplished in five longest linear sequences (LLS) starting from commercially available and inexpensive (-)-sclareol. The divergent translational potential of (+)-yahazunol was demonstrated by the expedient preparation of (-)-zonarone, (-)-isozonarone, (-)-zonarol, (-)-isozonarol, (+)-chromazonarol, and (+)-yahazunone. This approach also enables the formal synthesis of puupehenol, puupehedione, and hongoquercin A. Antifungal evaluation was performed, and this represents the first biological profiles for (+)-yahazunone, (+)-8- O-acetylyahazunone, and (+)-8- O-acetylyahazunol. (+)-Chromazonarol and (+)-yahazunone are promising candidates against Sclerotinia scleotiorum, with EC50 values of 24.1 and 28.7 μM, respectively, demonstrating advantages over the original model (DM) and synthesized heterocyclic mimic (3a) of meroterpenoids. This will favor the establishment of a chemical repertoire in the management of different plant diseases.