Concertedness and Activation Energy Control by Distal Methyl Group during Ring Contraction/Expansion in Scalarane‐Type Sesterterpenoid Biosynthesis
Concertedness and Activation Energy Control by Distal Methyl Group during Ring Contraction/Expansion in Scalarane‐Type Sesterterpenoid Biosynthesis
复制标题
卡拉烷型二倍萜生物合成中环收缩/扩张过程中远端甲基的一致性和活化能控制
DOI：
10.1002/chem.202203076
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Nakano Moe
中科院分区：
文献类型：
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作者：
Sato Hajime;Nakano Moe
Salmahyritisol A、similan A和spongide A是scalarane型二萜类化合物，具有6/6/5/7/5五环骨架。虽然它们的生物合成以前已经提出涉及一个独特的骨架重排反应，详细的反应机制仍然不清楚，因为没有相应的生物合成酶的反应已经报道。在此，使用计算技术研究了该骨架重排反应，其揭示了以下四个关键特征：（i）远端24-Me取代基控制该转化的协调性和活化能，（ii）酶不负责观察到的C12-C20键形成的区域选择性，（iii）立体选择性是酶调节的，和（iv）质子化是该骨架重排过程中的关键步骤。这些新的发现提供了对C环收缩和D环扩张机制在scalarane型二倍半萜类化合物生物合成的见解。
Salmahyritisol A, similan A, and hippospongide A, which are scalarane‐type sesterterpenoids, feature 6/6/5/7/5 pentacyclic skeletons. Although their biosyntheses have been previously proposed to involve a unique skeletal rearrangement reaction, the detailed reaction mechanism remains unclear as none of the corresponding biosynthetic enzymes for this reaction have been reported. Herein, this skeletal rearrangement reaction was investigated using computational techniques, which revealed the following four key features: (i) the distal 24‐Me substituent controls both the concertedness and activation energy of this transformation, (ii) enzymes are not responsible for the observed regioselectivity of C12−C20 bond formation, (iii) stereoselectivity is enzyme‐regulated, and (iv) protonation is a key step in this skeletal rearrangement process. These new findings provide insight into the C‐ring‐contraction and D‐ring‐expansion mechanisms in scalarane‐type sesterterpenoid biosyntheses.