Studies On The Chemical Constituents And Bioactivities Of Hypericum Longistylum Oliv

The genus Hypericum of Guttiferae is widely distributed in the world,the plants of this genus have been used as folk medicines for depressive disorders and heal wounds.Plants in the genus are rich in novel structures with pharmacologicactivities.The biologically activities of polycyclic prenylated acylphloroglucinols(PPAPs)have been reported to show antimicrobial,antiviral,anti-inflammatory,antioxidant and neuroprotective activities,which has attracted much attention from the wider public.In the course of searching for particular and biologically active PPAPs,the aerial parts of Hypericum longistylum Oliv.were phytochemically investigated,leading to the isolation and characterization of seventeen new PPAPs.Four novel12,13-seco-spirocyclic PPAPs,three new 6/6/5/5/5 heterocycle PPAPs,seven 6/7/5and 6/6/5 heterocycle acylphloroglucinol-based meroterpenoids and three 6/5heterocycle acylphloroglucinol derivatives were included.Compounds 1-4 represent the first examples of naturally occurring12,13-seco-spirocyclic PPAPs with an enolizable?,?'-tricarbonyl system.The planar structures of 1-3 were established by a combination of 1D and 2D NMR,HRESIMS data,and chemical derivatization.Their absolute configurations were defined using electronic circular dichroism(ECD)spectroscopy and X-ray crystallography.The O-methylation of compounds 1-3,coupled with comprehensive analyses of their X-ray diffraction data and variable-temperature ~1H NMR spectra,allowed us to propose a general mechanism underlying the formation of inseparable C-24 epimers of hyperilongenol A(1).The variable-temperature ~1H NMR spectra collected in different solvents,not only decipher the solvent effects on the enolizable?,?'-tricarbonyl enol protons,but also confirmed existence of enol tautomers of 1-3.The O-methylation of compounds(18?27)deciphered broadening of NMR signal of C-2 in 1-3 at the same time.The planar structures and relative configurations of 5-17were established by a combination of 1D,2D NMR and HRESIMS data.Compounds 5?7 contain the rare 6/6/5/5/5 heterocycle system of PPAPs,8?9 possess an unreported 6/7/5 heterocycle in acylphloroglucinol-based meroterpenoids,and the 6/6/5 heterocycle meroterpenoids and 6/5 ring systems are uncommon in PPAPs.In addition,the antibacterial activity and Acetylcholinesterase(AChE)inhibitory activity in vitro of some new compounds were evaluated.Among which,compound 2 exhibited potent antibacterial activity against Staphylococcus aureus subsp.Aureus(SARA)with MIC50 of 11.2?M.Compound 1 and 3 showed mild AChE inhibitory activities.A preliminary analysis of the structure-activity relationship of 1?3demonstrated that variation of the substitution pattern at C-23 of PPAPs will significantly affect their AChE inhibitory activity and antibacterial activity against SARA.The studies on the chemical constituents of Hypericum longistylum Oliv.from Enshi region,Hubei Province enriched the database of PPAPs,further enormously benefited for the structural determination of PPAPs with enolizable?-dicarbonyl system,and would contribute to the chemical constituents of the genus Hypericum.