米团花二倍半萜的骨架重排反应研究

天然产物经自然界长期进化选择，在生物体内通过一系列酶催化反应形成，是新型骨架活性分子发现的源泉。以化学方法探索生源合成途径中的关键转化对不同骨架天然产物的高效合成及解析其形成机制具有重要意义。植物二倍半萜是一类独特的稀有天然产物，目前仅报道150余个，结构新颖复杂，生物活性广泛，具有极高的研究价值。唇形科植物米团花中富含二倍半萜化合物，项目前期从云南产米团花中发现60余个新颖骨架Leu-Ⅰ型二倍半萜，与尼泊尔产米团花中报道的Leu-Ⅱ型二倍半萜完全不同。进一步研究发现，Leu-Ⅰ型骨架能在化学条件下经过两次连续的α-酮醇重排转化为Leu-Ⅱ型。基于此发现，本项目拟对上述两种类型二倍半萜之间的骨架重排反应进行深入研究，揭示其转化机理，发展新型重排反应，丰富二倍半萜骨架类型，挖掘其潜在生物活性，为该类独特天然产物的高效合成及合理利用奠定基础，并为解析不同骨架二倍半萜在植物中的形成机制提供参考。

Natural products are formed by living organisms during the long-term evolutionary process in nature, which are generally produced through a series of enzyme-catalyzed chemical reactions. Exploring the key transformation in biosynthetic pathway by chemical methods is of great significance for efficient synthesis of natural products with different skeletons and dissection of their biosynthetic mechanisms. Plant sesterterpenoids are a unique class of rare natural products, with only about 150 compounds reported so far. Due to their novel and complex chemical structures and broad bioactivities, these natural products have extremely high research value. The plant Leucosceptrum canum (Labiatae) is particularly rich of sesterterpenoids. In our previous research, more than 60 Leu-I type sesterterpenoids have been isolated and identified from L. canum collected in Yunnan, which are completely different from the Leu-II type sesterterpenoids reported from L. canum of Nepalese origin. Further study showed that the Leu-I type sesterterpenoids can be converted into the Leu-II type sesterterpenoids by two successive α-ketol rearrangements under chemical conditions. Based on these new findings, this project aims to uncover the mechanism of this conversion process through further in-depth investigation on skeletal rearrangement of the above two types of sesterterpenoids from L. canum. Hopefully, a new rearrangement reaction will be developed to enrich the skeletal types of sesterterpenoids and explore their biological activities. This research may provide a basis for highly efficient synthesis and rational utilization of this unique class of natural products, and help elucidate the biosynthetic mechanisms of sesterterpenoids with different skeletons in the plant L. canum.