RESUMO
Presilphiperfolane-type sesquiterpenes represent a unique group of atypical sesquiterpenoids characterized by their distinctive tricyclic structure. They have significant potential as lead compounds for pharmaceutical and agrochemical development. Herein, we utilized a transcriptomic approach to identify a terpene synthase (TPS) gene responsible for the biosynthesis of rare presilphiperfolane-type sesquiterpenes in Inula lineariifolia, designated as IlTPS1. Through phylogenetic analysis, we have identified the evolutionary conservation of key motifs, including RR(x)8W, DDxxD, and NSE/DTE in IlTPS1, which are shared with other tricyclic sesquiterpene synthases in the TPS-a subfamily of Asteraceae plants. Subsequent biochemical characterization of recombinant IlTPS1 revealed it to be a multiproduct enzyme responsible for the synthesis of various tricyclic sesquiterpene alcohols from farnesyl diphosphate (FPP), resulting in production of seven distinct sesquiterpenes. Mass spectrometry and nuclear magnetic resonance (NMR) spectrometry identified presilphiperfolan-8ß-ol and presilphiperfol-7-ene as predominant products. Furthermore, biological activity assays revealed that the products from IlTPS1 exhibited a potent antifungal activity against Nigrospora oryzae. Our study represents a significant advancement as it not only functionally identifies the first step enzyme in presilphiperfolane biosynthesis but also establishes the heterologous bioproduction of these unique sesquiterpenes.
Assuntos
Alquil e Aril Transferases , Filogenia , Sesquiterpenos , Sesquiterpenos/metabolismo , Alquil e Aril Transferases/metabolismo , Alquil e Aril Transferases/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fosfatos de Poli-Isoprenil/metabolismo , Asteraceae/metabolismo , Asteraceae/genéticaRESUMO
The synthesis of strained polycyclic systems from readily available precursors with a minimum number of steps and with regio- and stereochemical control constitutes an important synthetic challenge. Herein, we report a tandem reaction comprising Co-TMTU (tetramethyl thiourea)-catalyzed Pauson-Khand (PK) and 6π-electrocyclization reactions for the formation of the highly strained core of presilphiperfolanols. The developed chemistry has been applied to the total syntheses of 4-epi-presilphiperfolan-8-ol and 7-epi-presilphiperfolan-1-ol.
Assuntos
Sesquiterpenos/química , Tioureia/análogos & derivados , Catálise , Cristalografia por Raios X , Ciclização , Conformação Molecular , Sesquiterpenos/síntese química , Estereoisomerismo , Tioureia/químicaRESUMO
Phytochemical investigation on the aerial parts of Senecio hadiensis Forssk. led to the isolation of two new sesquiterpenoids, presilphiperfolan-2α,5α,8α-triol (1) and presilphiperfolan-2α,5α,8α,10α-tetraol (2) featuring the rare presilphiperfolane-type frameworks. The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic (1D- and 2D-NMR, HR-ESI-MS) methods and by comparison with the literature data. The isolates 1 and 2 were evaluated in-vitro for antiinflammatory, cytotoxic, and peroxisome proliferator activated receptor alpha and gamma (PPARα and PPARγ) agonistic activities.