Twelve new diterpenoids,euphorwallnoids A-L(1-12),comprising five rhamnofolanes(1-5),five tiglianes(6-10),and two daphnanes(11 and 12),along with six known analogues(13-18),were isolated from the whole plants of Eupho...Twelve new diterpenoids,euphorwallnoids A-L(1-12),comprising five rhamnofolanes(1-5),five tiglianes(6-10),and two daphnanes(11 and 12),along with six known analogues(13-18),were isolated from the whole plants of Euphorbia wallichii(E.wallichii).Their structures were determined using spectroscopic analysis,computational methods,chemical derivatization,and single-crystal X-ray diffraction.Euphorwallnoid A(1)features an unusual 5/7/6/5-tetracyclic scaffold,whereas 2-5 represent a rare subclass of 4-deoxygenated rhamnofolanes and 6-8 constitute 13-deoxygenated tiglianes.Notably,compound 1 demonstrated promising anti-liver fibrosis activity by significantly inhibiting the expression of fibronectin(FN),α-smooth muscle actin(α-SMA),and collagen I in transforming growth factorβ1(TGF-β1)-stimulated LX-2 cells at micromolar concentrations.展开更多
New-skeleton terpenoids have prompted considerable interest owing to their chemical and biological significance.A chemical study on the bark of Croton laui led to the isolation and identification of a new norsesterter...New-skeleton terpenoids have prompted considerable interest owing to their chemical and biological significance.A chemical study on the bark of Croton laui led to the isolation and identification of a new norsesterterpenoid,crolatinoid A(1),and two new neoclerodane diterpenoids,crolatinoids B and C(2 and 3).Structurally,compound 1 exhibits an unprecedented 12,17-cyclo20-nor phenyllabdane skeleton.Compound 2 features a novel 19(5→4)-abeo-3,5-cycloneoclerodane skeleton,which is hypothetically derived from precursor 3 through an oxa-di-π-methane rearrangement process.Furthermore,compound 1 demonstrated a significant capacity to reverse multidrug resistance in paclitaxel-resistant HCT-15 cells with a reversal fold value of 16.All three compounds displayed adipogenesis inhibition in 3T3-L1 adipocytes.展开更多
Many labdane-related diterpenoids(LRDs) exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrom...Many labdane-related diterpenoids(LRDs) exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome P450s(CYPs).The medicinal plant Euphorbia fischeriana Steud.is rich in LRDs with distinct scaffolds.Herein,we characterized three cytochrome P450s involved in LRD biosynthesis from this plant.Notably,CYP71D450 and CYP701A148 are two substrate-promiscuity CYPs.The former is the first example of CYPs which can oxidize C-3 of ent-atisane skeleton and ent-isopimara-7(8),15-diene,and the latter is the first example of CYPs which can oxidize C-19 of ent-abietane and ent-pimarane skeletons.This study expands the toolkit for bioproduction of diverse LRDs.展开更多
Owing to their intricate molecular frameworks and copious chiral centers,the structural identification and configurational assignment of natural products are challenging tasks.Comprehensive spectral data analysis is c...Owing to their intricate molecular frameworks and copious chiral centers,the structural identification and configurational assignment of natural products are challenging tasks.Comprehensive spectral data analysis is crucial for the confirmation of absolute configurations.Ignoring critical parameters will lead to false structure,which may confuse the total synthesis and drug development.Herein,the configurations of seven heterogeneous Pallavicinia diterpenoids(PDs) isolated from Pallavicinia liverworts are revised using a combination of single-crystal X-ray diffraction and electronic circular dichroism(ECD) calculations.Meanwhile,identification of five unprecedented PD heterodimers PD-dimers A-E(18-22) along with eleven previously undescribed PDs(5-9,13-17,23) obtained by the reinvestigation of the Chinese liverwort Pallavicinia subciliata have resulted in corrections and support the revised conclusions.展开更多
Continuous research on Cephalotaxus plants has ultimately led to the US food and drug administration (FDA) ap-provalof homoharringtonine in 2012 for the treatment of chronic myeloid leukemia. Additionally, another imp...Continuous research on Cephalotaxus plants has ultimately led to the US food and drug administration (FDA) ap-provalof homoharringtonine in 2012 for the treatment of chronic myeloid leukemia. Additionally, another important class of natural products from Cephalotaxus plants is cephalotane diterpenoids. Since the discovery of the first member, harring-tonolide,in 1978, cephalotane diterpenoids have garnered significant attention from the scientific community due to their re-markableanti-cancer activity. The unique structural features of cephalotane diterpenoids, a 7/6/5/6-fused tetracyclic carbon skeleton and a bridged lactone, make them ideal targets for synthetic chemists. Successfully synthesizing these complex diterpenoids is of great importance for the discovery and development of anti-tumor drugs. To date, ten research groups have completed the total synthesis of 24 cephalotane diterpenoids. The latest progress in the total synthesis of cephalotane diterpe-noidsis reviewed, showcasing the importance of these innovative synthetic strategies in the efficient synthesis of complex natural products and their potential significance in advancing the field of drug discovery.展开更多
A category of highly fused diterpenoid natural products possessing a characteristic perhydropyrene-like or rearranged tetracyclic skeleton structure are distributed in different life forms.Compared to traditional poly...A category of highly fused diterpenoid natural products possessing a characteristic perhydropyrene-like or rearranged tetracyclic skeleton structure are distributed in different life forms.Compared to traditional polycyclic diterpenoids,their biosynthetic pathways are quite unique and diverse.Chemists have pinpointed a range of this type of unusual diterpenoids:cycloamphilectanes and isocycloamphilectanes,kempenes and rippertanes,hydropyrene and hydropyrenol,along with recently disclosed cephalotanes.This review describes developments in this field and discusses the challenges associated with synthesizing this class of highly complex compounds.展开更多
This review covers the structures of diterpenoids,including chain(72),monocyclic(9),labdane-type(67),clerodane-type(127)abietane-type(716),ent-kaurane-type(89),grayanane-type(331),ingenanetype(55),tigliane-type(154),d...This review covers the structures of diterpenoids,including chain(72),monocyclic(9),labdane-type(67),clerodane-type(127)abietane-type(716),ent-kaurane-type(89),grayanane-type(331),ingenanetype(55),tigliane-type(154),daphnane-type(237),and aconitine-type diterpene alkaloids(265)with rich biological activities reported in 2013-2023.And the drugs in clinical use or under clinical investigation of diterpenoids and leading compounds were summarized.展开更多
Diabetic retinopathy,a prevalent and vision-threatening microvascular complication of diabetes mellitus,is the leading cause of blindness among middle-aged and elderly individuals.Natural diterpenoids isolated from Si...Diabetic retinopathy,a prevalent and vision-threatening microvascular complication of diabetes mellitus,is the leading cause of blindness among middle-aged and elderly individuals.Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties.This study aimed to identify novel bioactive diterpenoids from S.pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy,both in vitro and in vivo.Three new ent-pimarane-type diterpenoids(1–3)and six known compounds(4–9)were isolated from the aerial parts of S.pubescens.Their structures were elucidated through spectroscopic data interpretation,and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism(ECD)spectra.Among these compounds,14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene(5)exhibited the most potent protective effect against high glucose and interleukin-1β(IL-1β)-stimulated human retinal endothelial cells.Mechanistically,compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy,both in vivo and in vitro.These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S.pubescens,but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.展开更多
Six rearranged nor-diterpenoids with 5/6/6-fused tricyclic system(1–6),and one unprecedented dimer with 5/6/6/6/6/5-fused carbon core(7)were isolated from Strophioblachia glandulosa.Spectroscopic techniques,electroni...Six rearranged nor-diterpenoids with 5/6/6-fused tricyclic system(1–6),and one unprecedented dimer with 5/6/6/6/6/5-fused carbon core(7)were isolated from Strophioblachia glandulosa.Spectroscopic techniques,electronic circular dichroism(ECD),quantum chemical calculations,and single-crystal X-ray diffraction analysis were used to elucidate their structures.A preliminary bioactivity assay revealed compounds 2 and 3 exhibited potent anti-myocardial hypertrophy effect in vitro by significantly inhibiting the expression levels of atrial natriuretic peptide(ANP)and myosin heavy chain 7(MYH7)proteins.Additionally,mitogen-activated protein kinase 14(Mapk14)may be involved in the regulation of compound3 on cardiac hypertrophic disease by network pharmacology prediction and experimental verification.展开更多
Five previously undescribed diterpenoids,named succipenoids D‒H(1‒5),along with four undescribed lignans,named succignans A‒D(6‒9),were isolated from the dichloromethane extract of Chinese medicinal succinum.Compounds...Five previously undescribed diterpenoids,named succipenoids D‒H(1‒5),along with four undescribed lignans,named succignans A‒D(6‒9),were isolated from the dichloromethane extract of Chinese medicinal succinum.Compounds 1‒5 were characterized as nor-abietane diterpenoids,while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units.The structures of these novel compounds,including their absolute configurations,were determined through spectroscopic and computational methods.Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis,includingα-smooth muscle actin(α-SMA),collagen I,and fibronectin in transforming growth factor-β1(TGF-β1)induced normal rat kidney proximal tubular epithelial cells(NRK-52e).展开更多
Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce th...Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.展开更多
Eight new diterpenoids,Isodons A-H(1-8),comprising seco-abietane and abietane-type structures,together with 13 known analogues(9-21),were isolated from Isodon lophanthoides(Buch.-Ham.ex D.Don)Hara.The compounds(+)-3/(...Eight new diterpenoids,Isodons A-H(1-8),comprising seco-abietane and abietane-type structures,together with 13 known analogues(9-21),were isolated from Isodon lophanthoides(Buch.-Ham.ex D.Don)Hara.The compounds(+)-3/(-)-3,(+)-4/(-)-4,and(+)-5/(-)-5 were identified as three enantiomeric pairs.The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),1D&2D nuclear magnetic resonance(NMR)spectroscopy,electronic circular dichroism(ECD)calculations,and X-ray diffraction crystallography.A cholesterol 7α-hydroxylase(Cyp7a1)luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1,(+)-4,6,7,12-14,and 16.Additionally,compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor(FXR)-associated signaling pathways in vitro and in vivo.These findings suggest potential applications for I.Lophanthoides in pharmaceutical development.展开更多
One new ent-pimarane diterpenoid ent-16-nor-3-oxo-pimar-8（14）-en-15-al （1） together with four known diterpenoids kirenol （2）, ent-2-oxo-15,16,19-trihydroxypimar-8（14）-ene （3）, darutigenol （4） and darutosi...One new ent-pimarane diterpenoid ent-16-nor-3-oxo-pimar-8（14）-en-15-al （1） together with four known diterpenoids kirenol （2）, ent-2-oxo-15,16,19-trihydroxypimar-8（14）-ene （3）, darutigenol （4） and darutoside （5） were isolated from the ethanol extract of Siegesbeckia pubescens. The planar structures and relative configurations of these compounds were elucidated by comprehensive spectroscopic analysis.展开更多
The aim of current study was to investigate the chemical constituents of the needles of Taxus media. The isolation and purification of components were achieved by a series of chromatography including silica gel, Sepha...The aim of current study was to investigate the chemical constituents of the needles of Taxus media. The isolation and purification of components were achieved by a series of chromatography including silica gel, Sephadex LH-20, MCI and reversed- phase HPLC. Their structures were indentified based on 1D, 2D NMR, and mass spectral analysis. Seven taxane diterpenoids were isolated and identified as ll3,2tt,9ct,1013-tetrahydroxy-5ct-cinnamoyloxy-3,11-cyclotaxa-4（20）-en-13-one （1）, 2it, 7[3, 9ct, 1013, 13tt-pentaacetoxytaxa-4（20）, 11-dien-Sct-ol （2）, 2-deacetoxy-5-decinnamoyltaxinine J （3）, taxuspine F （4）, taxuspinanane K （5）, taxchin A （6）, and baccatin IV （7）. Among them, 1 is a new compound and compounds 2, 5, 6 and 7 are isolated from Taxus media for the first time.展开更多
Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates（1 and 2） and aconicarmichinium C chloride（3）,were isolated from an aqueous extract of ＂fu zi＂,the lateral root...Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates（1 and 2） and aconicarmichinium C chloride（3）,were isolated from an aqueous extract of ＂fu zi＂,the lateral roots of Aconitum carmichaelii.Their structures were elucidated by extensive spectroscopic data analysis.Compounds 1-3 represent the first examples of napelline-type C20 diterpenoid alkaloid alcohol iminiums,of which the structures were fully characterized.In addition,transformation and equilibration between the alcohol iminiums（1-3） and the aza acetals la-3a were investigated by measurements of the NMR spectra in protic and aprotic deuterium solvents including alkali pyridine-d5,along with evaporation under reduced pressure and gradual additions of TFA,AcOH,and HC1.The results demonstrated that the transformation and equilibration were solvent-,base-,and acid-dependent.Especially,in aqueous biological fluid,these C20-diterpenoid alkaloids would more likely exist as the alcohol iminiums accompanied by anion counterparts in biosystems to increase their solubility, bioavailability, transportations, and functions.The absolute configurations of 1-3 were confirmed by X-ray crystallographic analysis of 2a.展开更多
Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), ...Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), the structure of compound 1 was established to be 17-acetoxy-16alpha-ent-kauran-19-oic acid The other three known compounds were identified as ent-pimera-8(14) 15-dien-19-oic acid (2), 16alpha-hydroxy-( -)-kauran-19-oic acid (3) and 16alpha-17-dihydroxy-ent-kauran-19-oic acid (4). The three known diterpenoids were obtained from this plant for the first time.展开更多
Agastol (2), a new diterpene, was isolated from the roots of Agastache rugosa together with its isomer, named isoagastol (3) Their structures were established on the basis of spectral methods The structures of aga...Agastol (2), a new diterpene, was isolated from the roots of Agastache rugosa together with its isomer, named isoagastol (3) Their structures were established on the basis of spectral methods The structures of agastol (2) and isoagastol (3) was elucidated as 11,14 dihydroxy 12 methoxy 19(4→3) abeo abieta 4(18),8,11,13 tetraen 7 one and 11,14 dihydroxy 12 methoxy 19(4→3) abeo abieta 3,8,11,13 tetraen 7 one Isoagastol was isolated for the first time from natural sources展开更多
Normal-phase and reversed-phase silica gel column chromatography and semi-preparative high performance liquid chromatography were applied to study the chemical constituents of the stems and twigs of the Hainan mangrov...Normal-phase and reversed-phase silica gel column chromatography and semi-preparative high performance liquid chromatography were applied to study the chemical constituents of the stems and twigs of the Hainan mangrove plant,Excoecaria agallocha L.A new 3,4-seco-ent-kaurane diterpenoid,named agallochanin acid A(1),and a rare ent-tetranorlabdane diterpenoid,named agallochanin acid B(2),along with four known diterpenoids were isolated.Their structures including absolute configurations were characterized via HR-ESI-MS,extensive 1D and 2D NMR investigations and calculated and experimental electronic circular dichroism(ECD)data.All isolates were tested for their inhibitory effects on NO production in lipopolysaccharide(LPS)-activated BV-2 cells.ent-3,4-Seco-17-oxo-kaur-4(19),15(16)-dien-3-oic acid(3)and ent-15-hydroxy-labda-8(17),13E-dien-3-one(5)exhibited considerable anti-neuroinflammatory activities with IC50 values of(14.32±1.99)and(4.24±0.37)μmol/L.展开更多
Two new ent-rosane type diterpenoids, anomalusins A （1） and B （2）, together with ten known compounds were isolated from the plants of Mallotus anomalus Meer et Chun. The structures of compounds 1 and 2 were fully ...Two new ent-rosane type diterpenoids, anomalusins A （1） and B （2）, together with ten known compounds were isolated from the plants of Mallotus anomalus Meer et Chun. The structures of compounds 1 and 2 were fully elucidated on the basis of spectroscopic evidence, and CD analysis.展开更多
AIM:To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori(H.pylori)-infected inflammation,intestinal metaplasia,and nuclear factor kappa B(NF-κB)signaling pathway in vitro.METHODS:We u...AIM:To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori(H.pylori)-infected inflammation,intestinal metaplasia,and nuclear factor kappa B(NF-κB)signaling pathway in vitro.METHODS:We used I-type H.pylori to infect human gastric epithelial gastric epithelium cell line(GES-1)cell lines,and then H.pylori-infected GES-1 cells were treated with radix curcumae(RC)-derived diterpenoid C of different concentrations(5,10,20μg/mL)and amoxicillin.The expression of p65,IκB kinase(IKK)αand IKKγproteins was detected with Western blotting,and the expression of interleukin(IL)-8,IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method.Data were analyzed using SPSS software ver18.0.For comparisons between groups of more than two unpaired values,one-way analysis of variance(ANOVA)was used.If an ANOVA F value was significant,post hoc comparisons were performed between groups.If results were not normally distributed,the Mann-Whitney U test was used to compare two groups of unpaired values,whereas for comparisons between groups of more than two unpaired values,the Kruskal-Wallis H test was used.Statistical significance was established at P<0.05.RESULTS:The MTT assay results revealed the inhibited rate of GES-1,and indicated that the IC5 of RCderived diterpenoid C and amoxicillin all were 5μg/mL for gastric GES-1 cells.The expression of IL-8 was significantly increased,especially at 12 h time point;and the expression of IL-4 was decreased in H.pyloriinfected GES-1 cells.After H.pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin,the expression of IL-8was decreased at 12,24,48,72 h points(P<0.01),especially in high-concentration diterpenoid C(20μg/mL)group;and the expression of IL-4 was increased,especially in moderate and high-concentration diterpenoid C(10 and 20μg/mL)groups.RC-derived diterpenoid C had the inhibitory effects on H.pylori-induced p65 translocation from cytoplasm into cell nucleus,H.pylori-stimulant IkBαdegradation,the phosphorylation of p65 and IkBα,and the expression of IKKαand IKKβproteins.CONCLUSION:RC-derived diterpenoid C can block NF-κB signal pathway,effectively reducing the secretion of H.pylori-induced proinflammatory cytokine and increasing the secretion of anti-inflammatory cytokine.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82404454,22407144,82304322)the China Postdoctoral Science Foundation(No.2024M753800)+1 种基金the Postdoctoral Fellowship Program of CPSF(No.GZC20242113)the Open Program of Shenzhen Bay Laboratory(No.SZBL2021080601007)。
文摘Twelve new diterpenoids,euphorwallnoids A-L(1-12),comprising five rhamnofolanes(1-5),five tiglianes(6-10),and two daphnanes(11 and 12),along with six known analogues(13-18),were isolated from the whole plants of Euphorbia wallichii(E.wallichii).Their structures were determined using spectroscopic analysis,computational methods,chemical derivatization,and single-crystal X-ray diffraction.Euphorwallnoid A(1)features an unusual 5/7/6/5-tetracyclic scaffold,whereas 2-5 represent a rare subclass of 4-deoxygenated rhamnofolanes and 6-8 constitute 13-deoxygenated tiglianes.Notably,compound 1 demonstrated promising anti-liver fibrosis activity by significantly inhibiting the expression of fibronectin(FN),α-smooth muscle actin(α-SMA),and collagen I in transforming growth factorβ1(TGF-β1)-stimulated LX-2 cells at micromolar concentrations.
基金support from the National Key Research and Development Program of China(No.2023YFE0206100)the National Natural Science Foundation of China(Nos.22237007 and T2192972)+1 种基金the Youth Innovation Promotion Association of Chinese Academy of Sciences(CAS)(No.2022282)Shanghai Institute of Materia Medica of CAS(No.SIMM0120231002)is gratefully acknowledged.
文摘New-skeleton terpenoids have prompted considerable interest owing to their chemical and biological significance.A chemical study on the bark of Croton laui led to the isolation and identification of a new norsesterterpenoid,crolatinoid A(1),and two new neoclerodane diterpenoids,crolatinoids B and C(2 and 3).Structurally,compound 1 exhibits an unprecedented 12,17-cyclo20-nor phenyllabdane skeleton.Compound 2 features a novel 19(5→4)-abeo-3,5-cycloneoclerodane skeleton,which is hypothetically derived from precursor 3 through an oxa-di-π-methane rearrangement process.Furthermore,compound 1 demonstrated a significant capacity to reverse multidrug resistance in paclitaxel-resistant HCT-15 cells with a reversal fold value of 16.All three compounds displayed adipogenesis inhibition in 3T3-L1 adipocytes.
基金supported by grants from the National Natural Science Foundation of China [Nos.82474024,82293682 (82293680),82073953]the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (No.2021-RC350-009)+1 种基金the CAMS Innovation Fund for Medical Sciences (No.2023-I2M-2-006)the Special Fund for the Construction of Qinghai Innovation Platform (No.2024-ZJ-T02)。
文摘Many labdane-related diterpenoids(LRDs) exhibit high values in drug development.Their diversity in structure and bioactivity,to a large extent,arise from oxidative modifications which are mainly catalyzed by cytochrome P450s(CYPs).The medicinal plant Euphorbia fischeriana Steud.is rich in LRDs with distinct scaffolds.Herein,we characterized three cytochrome P450s involved in LRD biosynthesis from this plant.Notably,CYP71D450 and CYP701A148 are two substrate-promiscuity CYPs.The former is the first example of CYPs which can oxidize C-3 of ent-atisane skeleton and ent-isopimara-7(8),15-diene,and the latter is the first example of CYPs which can oxidize C-19 of ent-abietane and ent-pimarane skeletons.This study expands the toolkit for bioproduction of diverse LRDs.
基金supported by the National Natural Science Foundation of China (Nos.82293682,82293684,and 82173703)。
文摘Owing to their intricate molecular frameworks and copious chiral centers,the structural identification and configurational assignment of natural products are challenging tasks.Comprehensive spectral data analysis is crucial for the confirmation of absolute configurations.Ignoring critical parameters will lead to false structure,which may confuse the total synthesis and drug development.Herein,the configurations of seven heterogeneous Pallavicinia diterpenoids(PDs) isolated from Pallavicinia liverworts are revised using a combination of single-crystal X-ray diffraction and electronic circular dichroism(ECD) calculations.Meanwhile,identification of five unprecedented PD heterodimers PD-dimers A-E(18-22) along with eleven previously undescribed PDs(5-9,13-17,23) obtained by the reinvestigation of the Chinese liverwort Pallavicinia subciliata have resulted in corrections and support the revised conclusions.
文摘Continuous research on Cephalotaxus plants has ultimately led to the US food and drug administration (FDA) ap-provalof homoharringtonine in 2012 for the treatment of chronic myeloid leukemia. Additionally, another important class of natural products from Cephalotaxus plants is cephalotane diterpenoids. Since the discovery of the first member, harring-tonolide,in 1978, cephalotane diterpenoids have garnered significant attention from the scientific community due to their re-markableanti-cancer activity. The unique structural features of cephalotane diterpenoids, a 7/6/5/6-fused tetracyclic carbon skeleton and a bridged lactone, make them ideal targets for synthetic chemists. Successfully synthesizing these complex diterpenoids is of great importance for the discovery and development of anti-tumor drugs. To date, ten research groups have completed the total synthesis of 24 cephalotane diterpenoids. The latest progress in the total synthesis of cephalotane diterpe-noidsis reviewed, showcasing the importance of these innovative synthetic strategies in the efficient synthesis of complex natural products and their potential significance in advancing the field of drug discovery.
基金the National Natural Science Foundation of China(No.22471224)。
文摘A category of highly fused diterpenoid natural products possessing a characteristic perhydropyrene-like or rearranged tetracyclic skeleton structure are distributed in different life forms.Compared to traditional polycyclic diterpenoids,their biosynthetic pathways are quite unique and diverse.Chemists have pinpointed a range of this type of unusual diterpenoids:cycloamphilectanes and isocycloamphilectanes,kempenes and rippertanes,hydropyrene and hydropyrenol,along with recently disclosed cephalotanes.This review describes developments in this field and discusses the challenges associated with synthesizing this class of highly complex compounds.
文摘This review covers the structures of diterpenoids,including chain(72),monocyclic(9),labdane-type(67),clerodane-type(127)abietane-type(716),ent-kaurane-type(89),grayanane-type(331),ingenanetype(55),tigliane-type(154),daphnane-type(237),and aconitine-type diterpene alkaloids(265)with rich biological activities reported in 2013-2023.And the drugs in clinical use or under clinical investigation of diterpenoids and leading compounds were summarized.
基金supported by the National Natural Science Foundation of China (No.82073728)the Natural Science Foundation of Shandong Province (No.ZR2021MH357)。
文摘Diabetic retinopathy,a prevalent and vision-threatening microvascular complication of diabetes mellitus,is the leading cause of blindness among middle-aged and elderly individuals.Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties.This study aimed to identify novel bioactive diterpenoids from S.pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy,both in vitro and in vivo.Three new ent-pimarane-type diterpenoids(1–3)and six known compounds(4–9)were isolated from the aerial parts of S.pubescens.Their structures were elucidated through spectroscopic data interpretation,and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism(ECD)spectra.Among these compounds,14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene(5)exhibited the most potent protective effect against high glucose and interleukin-1β(IL-1β)-stimulated human retinal endothelial cells.Mechanistically,compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy,both in vivo and in vitro.These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S.pubescens,but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
基金supported financially by the National Natural Science Foundation of China(Nos.82260682,22477108,81960662,82200550)the Project of Yunnan Characteristic Plant Screening and R&D Service CXO Platform(No.2022YKZY001)+9 种基金the Yunnan Provincial Science and Technology Department(Nos.202101AT070154,202301AT0–70270 and 202401AY070001–303)the Scientific Research Fund Project of Yunnan Provincial Department of Education(No.2023Y0–797)the Program Innovative Research Team in Science and Technology in Kunming Medical University(No.CXTD202202)the Program for Changjiang Scholars and Innovative Research Team in University(No.IRT-17R94)the Project of Innovative Research Team of Yunnan Province(No.202005AE160005)the Open Research Foundation of Yunnan Key Laboratory of Bioactive Peptides in Yunnan Province(No.HXDT-2022–1)a grant(No.2023KF007)from YNCUBFirst-Class Discipline Team of Kunming Medical University(No.2024XKTDPY12)Yunnan Revitalization Talent Support Programthe Yun Ling Scholar Project to W.-L.Xiao。
文摘Six rearranged nor-diterpenoids with 5/6/6-fused tricyclic system(1–6),and one unprecedented dimer with 5/6/6/6/6/5-fused carbon core(7)were isolated from Strophioblachia glandulosa.Spectroscopic techniques,electronic circular dichroism(ECD),quantum chemical calculations,and single-crystal X-ray diffraction analysis were used to elucidate their structures.A preliminary bioactivity assay revealed compounds 2 and 3 exhibited potent anti-myocardial hypertrophy effect in vitro by significantly inhibiting the expression levels of atrial natriuretic peptide(ANP)and myosin heavy chain 7(MYH7)proteins.Additionally,mitogen-activated protein kinase 14(Mapk14)may be involved in the regulation of compound3 on cardiac hypertrophic disease by network pharmacology prediction and experimental verification.
基金supported by Shenzhen Fundamental Research Program(No.JCYJ20200109114003921).
文摘Five previously undescribed diterpenoids,named succipenoids D‒H(1‒5),along with four undescribed lignans,named succignans A‒D(6‒9),were isolated from the dichloromethane extract of Chinese medicinal succinum.Compounds 1‒5 were characterized as nor-abietane diterpenoids,while compounds 6‒9 were identified as lignans polymerized from two groups of phenylpropanoid units.The structures of these novel compounds,including their absolute configurations,were determined through spectroscopic and computational methods.Biological assessments of renal fibrosis demonstrated that compounds 6 and 7 effectively reduce the expression of proteins associated with renal fibrosis,includingα-smooth muscle actin(α-SMA),collagen I,and fibronectin in transforming growth factor-β1(TGF-β1)induced normal rat kidney proximal tubular epithelial cells(NRK-52e).
基金supported by the Qi-Huang Chief Scientist Program of the National Administration of Traditional Chinese Medicine(2020)the National Key Research and Development Program of China(No.2022YFC3501705)+1 种基金Shanghai Sailing Program(No.23YF1447500)the China Postdoctoral Science Foundation(No.2023M732335).
文摘Aconiti Lateralis Radix Praeparata(Fuzi)represents a significant traditional Chinese medicine(TCM)that exhibits both notable pharmacological effects and toxicity.Various processing methods are implemented to reduce the toxicity of raw Fuzi by modifying its toxic and effective components,primarily diterpenoid alkaloids.To comprehensively analyze the chemical variations between different Fuzi products,ultra-high performance liquid chromatography-linear ion trap quadrupole Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)was employed to systematically characterize Shengfuzi,Heishunpian and Baifupian.A total of 249 diterpenoid alkaloids present in Shengfuzi were identified,while only 111 and 61 in Heishunpian and Baifupian were detected respectively,indicating substantial differences among these products.An untargeted metabolomics approach combined with multivariate statistical analysis revealed 42 potential chemical markers.Through subsequent validation using 52 batches of commercial Heishunpian and Baifupian samples,8 robust markers distinguishing these products were identified,including AC1-propanoic acid-3OH,HE-glucoside,HE-hydroxyvaleric acid-2OH,dihydrosphingosine,N-dodecoxycarbonylvaline and three unknown compounds.Additionally,the MS imaging(MSI)technique was utilized to visualize the spatial distribution of chemical constituents in raw Fuzi,revealing how different processing procedures affect the chemical variations between Heishunpian and Baifupian.The distribution patterns of different diterpenoid alkaloid subtypes partially explained the chemical differences among products.This research provides valuable insights into the material basis for future investigations of different Fuzi products.
基金supported by the National Key R&D Program of China(No.2023YFD1601400)Jiangsu Outstanding Youth Fund Project(No.BK20231535)+2 种基金the National Natural Science Foundation of China(Nos.82074068 and 82430118)the Basic Research Project for the Development of Modern Industrial College of Traditional Chinese Medicine and Health at Lishui University,Specialized Research Funds from the State Key Laboratory of Natural Medicines,China Pharmaceutical University(SKLNMZZ2024JS25)the 111 Project(No.B18056)。
文摘Eight new diterpenoids,Isodons A-H(1-8),comprising seco-abietane and abietane-type structures,together with 13 known analogues(9-21),were isolated from Isodon lophanthoides(Buch.-Ham.ex D.Don)Hara.The compounds(+)-3/(-)-3,(+)-4/(-)-4,and(+)-5/(-)-5 were identified as three enantiomeric pairs.The planar structures and absolute configurations of 1-8 were determined through high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),1D&2D nuclear magnetic resonance(NMR)spectroscopy,electronic circular dichroism(ECD)calculations,and X-ray diffraction crystallography.A cholesterol 7α-hydroxylase(Cyp7a1)luciferase reporter assay revealed significant anti-cholestatic activities for compounds 1,(+)-4,6,7,12-14,and 16.Additionally,compound 6 demonstrated anti-cholestatic effects through the farnesoid X receptor(FXR)-associated signaling pathways in vitro and in vivo.These findings suggest potential applications for I.Lophanthoides in pharmaceutical development.
基金supported by the National Natural Science Foundation of China(Grant No.30973628)the National Science and Technology Project of China(Grant No.2012ZX09103201-022)
文摘One new ent-pimarane diterpenoid ent-16-nor-3-oxo-pimar-8（14）-en-15-al （1） together with four known diterpenoids kirenol （2）, ent-2-oxo-15,16,19-trihydroxypimar-8（14）-ene （3）, darutigenol （4） and darutoside （5） were isolated from the ethanol extract of Siegesbeckia pubescens. The planar structures and relative configurations of these compounds were elucidated by comprehensive spectroscopic analysis.
基金National Natural Science Foundation of China(Grant No.30973628)
文摘The aim of current study was to investigate the chemical constituents of the needles of Taxus media. The isolation and purification of components were achieved by a series of chromatography including silica gel, Sephadex LH-20, MCI and reversed- phase HPLC. Their structures were indentified based on 1D, 2D NMR, and mass spectral analysis. Seven taxane diterpenoids were isolated and identified as ll3,2tt,9ct,1013-tetrahydroxy-5ct-cinnamoyloxy-3,11-cyclotaxa-4（20）-en-13-one （1）, 2it, 7[3, 9ct, 1013, 13tt-pentaacetoxytaxa-4（20）, 11-dien-Sct-ol （2）, 2-deacetoxy-5-decinnamoyltaxinine J （3）, taxuspine F （4）, taxuspinanane K （5）, taxchin A （6）, and baccatin IV （7）. Among them, 1 is a new compound and compounds 2, 5, 6 and 7 are isolated from Taxus media for the first time.
基金Financial support from the National Natural Science Foundation of China (NNSFC Nos. 21132009, 30825044)the National Science and Technology Project of China (Nos. 2012ZX09301002002, 2011ZX0 9307-002-01)
文摘Three new napelline-type C20-diterpenoid alkaloids,named aconicarmichinium A and B trifluoroacetates（1 and 2） and aconicarmichinium C chloride（3）,were isolated from an aqueous extract of ＂fu zi＂,the lateral roots of Aconitum carmichaelii.Their structures were elucidated by extensive spectroscopic data analysis.Compounds 1-3 represent the first examples of napelline-type C20 diterpenoid alkaloid alcohol iminiums,of which the structures were fully characterized.In addition,transformation and equilibration between the alcohol iminiums（1-3） and the aza acetals la-3a were investigated by measurements of the NMR spectra in protic and aprotic deuterium solvents including alkali pyridine-d5,along with evaporation under reduced pressure and gradual additions of TFA,AcOH,and HC1.The results demonstrated that the transformation and equilibration were solvent-,base-,and acid-dependent.Especially,in aqueous biological fluid,these C20-diterpenoid alkaloids would more likely exist as the alcohol iminiums accompanied by anion counterparts in biosystems to increase their solubility, bioavailability, transportations, and functions.The absolute configurations of 1-3 were confirmed by X-ray crystallographic analysis of 2a.
文摘Four diterpenoids, including a new ent-kaurane diterpene (1), were isolated from the rhizome of Aralia fargesii Franch. On the basis of chemical and spectral evidence (IR, EI-MS, HREI-MS, H-1-NMR, C-13-NMR and HMQC), the structure of compound 1 was established to be 17-acetoxy-16alpha-ent-kauran-19-oic acid The other three known compounds were identified as ent-pimera-8(14) 15-dien-19-oic acid (2), 16alpha-hydroxy-( -)-kauran-19-oic acid (3) and 16alpha-17-dihydroxy-ent-kauran-19-oic acid (4). The three known diterpenoids were obtained from this plant for the first time.
文摘Agastol (2), a new diterpene, was isolated from the roots of Agastache rugosa together with its isomer, named isoagastol (3) Their structures were established on the basis of spectral methods The structures of agastol (2) and isoagastol (3) was elucidated as 11,14 dihydroxy 12 methoxy 19(4→3) abeo abieta 4(18),8,11,13 tetraen 7 one and 11,14 dihydroxy 12 methoxy 19(4→3) abeo abieta 3,8,11,13 tetraen 7 one Isoagastol was isolated for the first time from natural sources
文摘Normal-phase and reversed-phase silica gel column chromatography and semi-preparative high performance liquid chromatography were applied to study the chemical constituents of the stems and twigs of the Hainan mangrove plant,Excoecaria agallocha L.A new 3,4-seco-ent-kaurane diterpenoid,named agallochanin acid A(1),and a rare ent-tetranorlabdane diterpenoid,named agallochanin acid B(2),along with four known diterpenoids were isolated.Their structures including absolute configurations were characterized via HR-ESI-MS,extensive 1D and 2D NMR investigations and calculated and experimental electronic circular dichroism(ECD)data.All isolates were tested for their inhibitory effects on NO production in lipopolysaccharide(LPS)-activated BV-2 cells.ent-3,4-Seco-17-oxo-kaur-4(19),15(16)-dien-3-oic acid(3)and ent-15-hydroxy-labda-8(17),13E-dien-3-one(5)exhibited considerable anti-neuroinflammatory activities with IC50 values of(14.32±1.99)and(4.24±0.37)μmol/L.
文摘Two new ent-rosane type diterpenoids, anomalusins A （1） and B （2）, together with ten known compounds were isolated from the plants of Mallotus anomalus Meer et Chun. The structures of compounds 1 and 2 were fully elucidated on the basis of spectroscopic evidence, and CD analysis.
基金Supported by The Natural Science Foundation of Zhejiang Province of China,No.LY12H29002by grants of Scientific Research from Chinese Herbal Drug Administration,No.2011ZB032
文摘AIM:To study effect of diterpenoid C extracted from radix curcumae on Helicobacter pylori(H.pylori)-infected inflammation,intestinal metaplasia,and nuclear factor kappa B(NF-κB)signaling pathway in vitro.METHODS:We used I-type H.pylori to infect human gastric epithelial gastric epithelium cell line(GES-1)cell lines,and then H.pylori-infected GES-1 cells were treated with radix curcumae(RC)-derived diterpenoid C of different concentrations(5,10,20μg/mL)and amoxicillin.The expression of p65,IκB kinase(IKK)αand IKKγproteins was detected with Western blotting,and the expression of interleukin(IL)-8,IL-6 and IL-4 was determined with enzyme-linked immunosorbent assay method.Data were analyzed using SPSS software ver18.0.For comparisons between groups of more than two unpaired values,one-way analysis of variance(ANOVA)was used.If an ANOVA F value was significant,post hoc comparisons were performed between groups.If results were not normally distributed,the Mann-Whitney U test was used to compare two groups of unpaired values,whereas for comparisons between groups of more than two unpaired values,the Kruskal-Wallis H test was used.Statistical significance was established at P<0.05.RESULTS:The MTT assay results revealed the inhibited rate of GES-1,and indicated that the IC5 of RCderived diterpenoid C and amoxicillin all were 5μg/mL for gastric GES-1 cells.The expression of IL-8 was significantly increased,especially at 12 h time point;and the expression of IL-4 was decreased in H.pyloriinfected GES-1 cells.After H.pylori-infected GES-1 cells were treated with RC-derived diterpenoid C of different concentrations and amoxicillin,the expression of IL-8was decreased at 12,24,48,72 h points(P<0.01),especially in high-concentration diterpenoid C(20μg/mL)group;and the expression of IL-4 was increased,especially in moderate and high-concentration diterpenoid C(10 and 20μg/mL)groups.RC-derived diterpenoid C had the inhibitory effects on H.pylori-induced p65 translocation from cytoplasm into cell nucleus,H.pylori-stimulant IkBαdegradation,the phosphorylation of p65 and IkBα,and the expression of IKKαand IKKβproteins.CONCLUSION:RC-derived diterpenoid C can block NF-κB signal pathway,effectively reducing the secretion of H.pylori-induced proinflammatory cytokine and increasing the secretion of anti-inflammatory cytokine.
