Two pairs of novel 6/6/6/9 tetracyclic merosesquiterpenoid enantiomers,dauroxonanols A(1)and B(2),possessing an unprecedented 9,15-dioxatetracyclo[8.5.3.0^(4.17).0^(14.18)]octadecane core skeleton,were isolated from R...Two pairs of novel 6/6/6/9 tetracyclic merosesquiterpenoid enantiomers,dauroxonanols A(1)and B(2),possessing an unprecedented 9,15-dioxatetracyclo[8.5.3.0^(4.17).0^(14.18)]octadecane core skeleton,were isolated from Rhododendron dauricum.The nuclear magnetic resonance(NMR)spectra of 1 and 2 showed very broad resonances,and^(13)C NMR spectrum of 1 exhibited only 13 instead of 22 carbon resonances.These broadening or missing NMR resonances led to a great challenge to elucidate their structures using NMR data analysis.Their structures and absolute configurations of 1 and 2 were finally determined by single crystal X-ray diffraction analysis,chiral separation,and electronic circular dichroism(ECD)calculations.Plausible biosynthetic pathways for 1 and 2 are proposed.Conformational analysis,density functional theory(DFT)calculations,and dynamic NMR assigned the coalescent NMR phenomena of 1 and 2 to the conformational changes of the flexible oxonane ring.Dauroxonanols A(1)and B(2)showed potentα-glucosidase inhibitory activities,2-8 times potent than acarbose,an antidiabetic drug targetingα-glucosidase in clinic.展开更多
Pyrrolobenzoxazines are a rare terpene-amino acid family of natural products with potent biological activities.Here,we reported the full biosynthetic pathway of paeciloxazine(1),a typical pyrrolobenzoxazine,with signi...Pyrrolobenzoxazines are a rare terpene-amino acid family of natural products with potent biological activities.Here,we reported the full biosynthetic pathway of paeciloxazine(1),a typical pyrrolobenzoxazine,with significant insecticidal activity.Base on heterologous expression,chemical complement experiment,and in vitro biochemical assays,we demonstrated the sesquiterpene portion of 1 derived from discontinuously oxidations of amorphdiene,in which P450 monooxygenase PaxH catalyzed a cascade of hydroxylation and epoxidation,while two flavin dependent monooxygenases are involved in the transformation of the esterified tryptophan into a pyrrolobenzoxazine core.Furthermore,a total of 15 compounds were generated through heterologous expression,of which 13,17 and 20 showed potential antiepileptic activity.This study fully elucidated the biosynthetic pathway of paeciloxazine(1)and showed the diversity and complexity of constructing natural products by organisms.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22207036,22277034,22477034,and 22107033)Interdisciplinary Research Program of Huazhong University of Science and Technology(No.2023JCYJ037)International Cooperation Project of Hubei Provincial Key R&D Plan(No.2023EHA040)。
文摘Two pairs of novel 6/6/6/9 tetracyclic merosesquiterpenoid enantiomers,dauroxonanols A(1)and B(2),possessing an unprecedented 9,15-dioxatetracyclo[8.5.3.0^(4.17).0^(14.18)]octadecane core skeleton,were isolated from Rhododendron dauricum.The nuclear magnetic resonance(NMR)spectra of 1 and 2 showed very broad resonances,and^(13)C NMR spectrum of 1 exhibited only 13 instead of 22 carbon resonances.These broadening or missing NMR resonances led to a great challenge to elucidate their structures using NMR data analysis.Their structures and absolute configurations of 1 and 2 were finally determined by single crystal X-ray diffraction analysis,chiral separation,and electronic circular dichroism(ECD)calculations.Plausible biosynthetic pathways for 1 and 2 are proposed.Conformational analysis,density functional theory(DFT)calculations,and dynamic NMR assigned the coalescent NMR phenomena of 1 and 2 to the conformational changes of the flexible oxonane ring.Dauroxonanols A(1)and B(2)showed potentα-glucosidase inhibitory activities,2-8 times potent than acarbose,an antidiabetic drug targetingα-glucosidase in clinic.
基金supported financially by the National Natural Science Foundation of China(Nos.22107122 and 82225042)the CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021I2M-1-029)。
文摘Pyrrolobenzoxazines are a rare terpene-amino acid family of natural products with potent biological activities.Here,we reported the full biosynthetic pathway of paeciloxazine(1),a typical pyrrolobenzoxazine,with significant insecticidal activity.Base on heterologous expression,chemical complement experiment,and in vitro biochemical assays,we demonstrated the sesquiterpene portion of 1 derived from discontinuously oxidations of amorphdiene,in which P450 monooxygenase PaxH catalyzed a cascade of hydroxylation and epoxidation,while two flavin dependent monooxygenases are involved in the transformation of the esterified tryptophan into a pyrrolobenzoxazine core.Furthermore,a total of 15 compounds were generated through heterologous expression,of which 13,17 and 20 showed potential antiepileptic activity.This study fully elucidated the biosynthetic pathway of paeciloxazine(1)and showed the diversity and complexity of constructing natural products by organisms.
