Synthesis And Antifungal Activity Of (+)-Chromazonarol And Analogues

Natural products are an important resource for the creation of new pesticides.Taking active natural products as the precursor is an important method for the development of new pesticides.Drimane-related meroterpenoids have attracted increasing attention,since they possess a wide range of biological activities,including antifungal,antibacterial,antiviral,antitumor,algicidal,antifeedant activities.Our previous work showed Drimane-related meroterpenoids have significant inhibitory effect on plant pathogenic fungi.So far,no structural modification and antibacterial activity studies have been carried out with(+)-Chromazonarol.Herein,(+)-Chromazonarol analogues were designed,synthesized and evaluated against a number of plant pathogens The results were as follows,(1)The natural product(+)-chromazonarol was synthesized with Barton decarboxylative coupling as a key step,starting from the cheap and readily available sclareol.Structural elucidation of(+)-Chromazonarol were carried out by Electrospray Ionization Mass Spectrometer(ESI-Mass),1H-Nuclear Magnetic Resonance(,H-NMR)Spectroscopy,13C-Nuclear Magnetic Resonance(13C-NMR)Spectroscopy.(2)20 Drimane-related meroterpenoids analogues of(+)-chromazonarol were synthesized,through etherification,esterification,or chlorination.All the target compounds were reported for the first time.Structural elucidation of all the targets compounds were carried out by Electrospray Ionization Mass Spectrometer(ESI-Mass),1H-Nuclear Magnetic Resonance(1H-NMR)Spectroscopy,13C-Nuclear Magnetic Resonance(13C-NMR)Spectroscopy.The Structure of compound 2a was also demonstrated by X-ray single-crystal diffraction.(3)The in vitro antifungal activity of the target compounds was determined by the mycelial growth method,against six plant pathogens,including Rhizoctonia solani,Sclerotinia sclerotiorum,Botrytis cinerea,Fusarium graminearum,Alternaria solani,Gaeumanomyce graminsis.The results showed that the antifungal activity of the derivatives against Sclerotinia sclerotiorum and Rhizoctonia was decreased compared with the parent compound(+)-chromazonarol.It was confirmed that the hydroxyl group on the benzene ring of(+)-chromazonarol is essential for the antifungal inhibitory activity.In addition,a preliminary interpretation of this through molecular docking.In summary,the Synthesis of natural product(+)-Chromazonarol was completed.20 analogues were designed and synthesized,and the antifungal activity was studied.It was confirmed that the hydroxyl group on the benzene ring of(+)-chromazonarol is essential for the antifungal inhibitory activity,which laid a foundation for the further structural optimization of the drimane-related meroterpenoids in the discovery of novel antifungal candidates based on(+)-Chromazonarol.