C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids.Therefore,theselective installation of prenyl group at C2 position of NH indoles is of great significance.However,the known protocols ge...C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids.Therefore,theselective installation of prenyl group at C2 position of NH indoles is of great significance.However,the known protocols generally require a multi‐step procedure and stoichiometric promoters.Hereinwe develop a one‐step C2 prenylation of NH indole with cheap tert‐prenyl alcohol enabled by acidcatalysis.Salient features include good regioselectivity,step‐and atom‐economy,broad substratescope,and simple catalytic system.The mechanistic investigations demonstrate that both C2prenylation and C3 prenylation/migration pathways are engaged in the reaction.Notably,this practicalstrategy can be applied to the late‐stage diversification of tryptophan‐based peptides and concisesynthesis of tryprostatin B.展开更多
As important natural and pharmaceutical motifs,the catalytic construction of structurally diverse 3,3-disubstituted oxindoles often requires elaborate synthetic efforts on optimizations.Herein,we developed a simple an...As important natural and pharmaceutical motifs,the catalytic construction of structurally diverse 3,3-disubstituted oxindoles often requires elaborate synthetic efforts on optimizations.Herein,we developed a simple and divergent approach for constructing reverse-prenylated and prenylated oxindoles launched by Ni catalysis with bulk chemical isoprene.Using C3-unsubstituted oxindoles as starting materials,mono reverse-prenylation was demonstrated in high chemo-and regioselectivities facilitated by the combination of Ni(0)and monodentate phosphine ligand.Using the obtained reverse-prenylated oxindoles as versatile synthon,substitutions at the pseudobenzylic position with various electrophiles created vicinal quaternary centers in a concise way.With the help of additives(PPh3 and NaH),air could be directly used as green oxidant to construct prenylated and reverse-prenylatedα-hydroxy-oxindoles divergently from the same substrates.In situ esterification of prenylatedα-hydroxy-oxindoles allowed subsequent Friedel-Crafts substitutions with diverse nucleophiles to deliver prenyl substituted dimeric or spiro-oxindoles.This protocol provides a divergent synthetic approach for the construction of highly functionalized 3,3-disubstituted oxindoles,which have been otherwise difficult to access in a unified approach.展开更多
The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophos...The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate(FPP) or geranylgeranyl pyrophosphate(GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess Caa X motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase(GGPPS) catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.展开更多
In the present study,17 flavonoids,including 9 prenylated isoflavones,4 isoflavones,3 flavanones and 1 flavone,were isolated from the twigs and leaves of Erythrina variegata.By NMR spectroscopic means and comparision ...In the present study,17 flavonoids,including 9 prenylated isoflavones,4 isoflavones,3 flavanones and 1 flavone,were isolated from the twigs and leaves of Erythrina variegata.By NMR spectroscopic means and comparision with the data in the leteratures,their structures were elucidated to be euchrenone b10(1),senegalensin(2),erythrinin C(3),scandenone(4),osajin(5),alpinum isoflavone(6),isoerysenegalensein E(7),erysenegalensein E(8),diprenylgenistein(9),abyssinone V(10),abyssinone V 4′-methyl ether(11),4′,7-dihydroxyflavanone(12),3′,5,7-trihydroxy-4′-methoxyisoflavone(13),2′,4′,5,7-tetrahydroxyisoflavone(14),genistein(15),daidzein(16),and apigenin(17).Except for compounds 1,4-7,and 9-10,other compounds were isolated from E.variegata for the first time.展开更多
AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).METHODS: Medical records were revie...AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).METHODS: Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confi rmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral titers.RESULTS: Median HCV RNA titers did not signif icantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL).For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no signif icant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with signif icantly lower viral titers (P < 0.05).CONCLUSION: There was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.展开更多
Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol cond...Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.展开更多
Protein prenylation plays a crucial role in plant development and stress response.We report the function of pren yltra nsferase a-sub unit in rice.Protein-protei n in teractions showed that the fam esyl-transferase(Os...Protein prenylation plays a crucial role in plant development and stress response.We report the function of pren yltra nsferase a-sub unit in rice.Protein-protei n in teractions showed that the fam esyl-transferase(OsPFT)/geranylgeranyltransferase-l(OsPGGT l-a)protein interacted together with OsPFT-P and OsPGGT l-p.The a-and p-subunits of OsPFT formed a heterodimer for the transfer of a farnesyl group from famesyl pyrophosphate to the CaaX-box-containing peptide N-dansyl-GCVLS.Furthermore,the tissue expressi on patter ns of the OsPFT and OsPGGT I sub units were similar,and these sub units were localized in the cytoplasm and nucleus.Moreover,OsPFT/OsPGGT/-a-deletion homozygous rice mutants had a lethal phenotype,and the heterozygous mutants exhibited reduced pollen viability.These results indicated that prenylation plays an important role in rice development.展开更多
C-glycosylation and C-prenylation are two important C-C-bond forming reactions for preparation,diversification and structural modification of natural/unnatural products with pharmacological activities.Here,we describe...C-glycosylation and C-prenylation are two important C-C-bond forming reactions for preparation,diversification and structural modification of natural/unnatural products with pharmacological activities.Here,we described unprecedented enzymatic cascades to C-glycosylate/prenylate different acyl resorcinol derivatives in stepwise,one-pot reactions by combining two promiscuous enzymes,MiCGT,a C-glycosyltransferase,and AtaPT,a prenyltransferase.Five novel bis-C-alkylated products were obtained and structurally identified by MS and NMR spectroscopic data as well as comparison with the literature.This study provided a potential synthetic strategy for synthesizing structurally novel and diverse compounds bearing both C-glycosyl and C-prenyl moieties by a two-step,enzymatic bis-C-alkylation.展开更多
Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangusto...Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangustone A（IAA） from licorice（Glycyrrhiza uralensis）, which induces apoptosis in colorectal cancer cells by disrupting mitochondrial functions. In the present study, we compared a group of flavonoids from licorice with IAA for their anti-proliferation activities and effects on intracellular signaling. The results indicated that the isoprenyl groups on the A and B rings, the hydroxyl groups at the ortho position of isoprenyl on A ring and the conjugated plane of C ring might contribute to the anti-cancer activity of prenylated flavonoids. Based on the above structure-activity relationship, we further identified four prenylated flavonoids with similar anti-cancer activities from licorice. Taken together, our present study established a preliminary structure-activity relationship of anti-cancer prenylated flavonoids, and our data provided important leading compounds from licorice, which deserved further research and development.展开更多
Four prenylated flavonoids compounds 1-4,named sinopodophyllines A-D,and a flavonoid glycoside(compound 13),sinopodophylliside A,together with 19 known compounds(compounds 5-12 and 14-24) were isolated from the fruits...Four prenylated flavonoids compounds 1-4,named sinopodophyllines A-D,and a flavonoid glycoside(compound 13),sinopodophylliside A,together with 19 known compounds(compounds 5-12 and 14-24) were isolated from the fruits of Sinopodophyllum hexandrum.The structures of new compounds were elucidated by extensive spectroscopic analysis,including HRESIMS,1D and 2D NMR.Compounds 1-6,9-11,and 14-17 were tested for their cytotoxicity against human breast-cancer T47 D,MCF-7 and MDA-MB-231 cells in vitro,and compounds 2,5,6,10 and 11 showed significant cytotoxicity(IC50 values < 10 μmol·L^(-1))against T47 D cells.展开更多
Six new prenylated flavonoid glycosides,including four new furan-flavonoid glycosides wushepimedoside A–D(1–4)and two new prenyl flavonoid derivatives wushepimedoside E–F(5–6),and one know analog epimedkoreside B(...Six new prenylated flavonoid glycosides,including four new furan-flavonoid glycosides wushepimedoside A–D(1–4)and two new prenyl flavonoid derivatives wushepimedoside E–F(5–6),and one know analog epimedkoreside B(7)were isolated from biotransformation products of the aerial parts of Epimedium wushanense.Their structures were elucidated according to comprehensive analysis of HR-MS and NMR spectroscopic data,and the absolute configurations were assigned using experimental and calculated electronic circular dichroism(ECD)data.The regulatory activity of compounds 1–7 on the production of testosterone in primary rat Leydig cells were investigated,and 4 and 5 exhibited testosterone production-promoting activities.Molecular docking analysis suggested that bioactive compounds 4 and 5 showed the stable binding with 3β-HSD and 4 also had good affinity with Cyp17A1,which suggested that these compounds may regulate testosterone production through stimulating the expression of the above two key proteins.展开更多
In continuation of our chemical investigation on some medicinal plants of the genus Tephrosia, re-investigation of the methylenechloride/methanol （1：1） extract of the air-dried aerial part of Tephrosia apollinea af...In continuation of our chemical investigation on some medicinal plants of the genus Tephrosia, re-investigation of the methylenechloride/methanol （1：1） extract of the air-dried aerial part of Tephrosia apollinea afforded a new prenylated flavonoid 1, in addition to an aromatic ester, a sesquiterpene, a lignan and several known prenylated flavonoids. The structures were established by （^1H NMR, ^13C NMR, DEPT, ^1H-^1H COSY, HMQC, HMBC, NOESY and HRMS）. Relative configurations of 9 and 10 were confirmed by X-ray analysis.展开更多
A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, I...A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, IR, MS, NMR and 1H-1H COSY) and confirmed by total synthesis.展开更多
Three new compounds named (2E)prenyl benzoate-4-O-α-L-arabinopyranosyl (1→6) β-D-glucopyranoside (1), 7-methoxy-8-O-β-D-glucopyranosyl coumarin (2), and 3,4'-dihydroxy-3'-methoxy benzenepentanoic acid (3) ...Three new compounds named (2E)prenyl benzoate-4-O-α-L-arabinopyranosyl (1→6) β-D-glucopyranoside (1), 7-methoxy-8-O-β-D-glucopyranosyl coumarin (2), and 3,4'-dihydroxy-3'-methoxy benzenepentanoic acid (3) were isolated from the leaves of Acanthopanax senticosus Harms. The structures of new compounds were determined by means of 2D NMR experiments and chemical methods.展开更多
2-[3,5-Di-O-β-D-glucosyl-4-(3-methylbut-2-enyl)phenyl]benzofuran-6-ol,a new prenylated arylbenzofuran derivative was isolated from Morus alba L.Its structure was elucidated by various spectroscopic methods including ...2-[3,5-Di-O-β-D-glucosyl-4-(3-methylbut-2-enyl)phenyl]benzofuran-6-ol,a new prenylated arylbenzofuran derivative was isolated from Morus alba L.Its structure was elucidated by various spectroscopic methods including MS,~1H NMR,^(13)C NMR,DEPT,~1H-~1HCOSY,HMQC and HMBC.展开更多
Two new dihydroflavonoids were obtained from the traditional Chinese medicinal herb Patrinia villosa Juss. Their structures were elucidated as （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6, 8-di （γ, γ-dimethylallyl） flavan...Two new dihydroflavonoids were obtained from the traditional Chinese medicinal herb Patrinia villosa Juss. Their structures were elucidated as （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6, 8-di （γ, γ-dimethylallyl） flavanone （1） and （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6-1avandulylated flavanone （2） by spectroscopic methods including UV, IR, HR-TOF-MS, 1D NMR and 2D NMR techniques.展开更多
Five new flavonoid derivatives,cajavolubones A-E(1-5),along with six known analogues(6-11)were isolated from Cajanus volubilis,and their structures were elucidated by spectroscopic analysis and quantum chemical calcul...Five new flavonoid derivatives,cajavolubones A-E(1-5),along with six known analogues(6-11)were isolated from Cajanus volubilis,and their structures were elucidated by spectroscopic analysis and quantum chemical calculations.Cajavolubones A and B(1 and 2)were identified as two geranylated chalcones.Cajavolubone C(3)was a prenylated flavone,while cajavolubones D and E(4 and 5)were two prenylated isoflavanones.Compounds 3,8,9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.展开更多
An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssino...An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.展开更多
文摘C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids.Therefore,theselective installation of prenyl group at C2 position of NH indoles is of great significance.However,the known protocols generally require a multi‐step procedure and stoichiometric promoters.Hereinwe develop a one‐step C2 prenylation of NH indole with cheap tert‐prenyl alcohol enabled by acidcatalysis.Salient features include good regioselectivity,step‐and atom‐economy,broad substratescope,and simple catalytic system.The mechanistic investigations demonstrate that both C2prenylation and C3 prenylation/migration pathways are engaged in the reaction.Notably,this practicalstrategy can be applied to the late‐stage diversification of tryptophan‐based peptides and concisesynthesis of tryprostatin B.
文摘As important natural and pharmaceutical motifs,the catalytic construction of structurally diverse 3,3-disubstituted oxindoles often requires elaborate synthetic efforts on optimizations.Herein,we developed a simple and divergent approach for constructing reverse-prenylated and prenylated oxindoles launched by Ni catalysis with bulk chemical isoprene.Using C3-unsubstituted oxindoles as starting materials,mono reverse-prenylation was demonstrated in high chemo-and regioselectivities facilitated by the combination of Ni(0)and monodentate phosphine ligand.Using the obtained reverse-prenylated oxindoles as versatile synthon,substitutions at the pseudobenzylic position with various electrophiles created vicinal quaternary centers in a concise way.With the help of additives(PPh3 and NaH),air could be directly used as green oxidant to construct prenylated and reverse-prenylatedα-hydroxy-oxindoles divergently from the same substrates.In situ esterification of prenylatedα-hydroxy-oxindoles allowed subsequent Friedel-Crafts substitutions with diverse nucleophiles to deliver prenyl substituted dimeric or spiro-oxindoles.This protocol provides a divergent synthetic approach for the construction of highly functionalized 3,3-disubstituted oxindoles,which have been otherwise difficult to access in a unified approach.
基金supported by the National Basic Research Program of China(2012CB524900,2009CB918703)National Natural Science Foundation of China(31271540,30671086)awarded to Li Chao Jun
文摘The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate(FPP) or geranylgeranyl pyrophosphate(GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess Caa X motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase(GGPPS) catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.
基金National Natural Science Foundation of China(Grant No.32060099).
文摘In the present study,17 flavonoids,including 9 prenylated isoflavones,4 isoflavones,3 flavanones and 1 flavone,were isolated from the twigs and leaves of Erythrina variegata.By NMR spectroscopic means and comparision with the data in the leteratures,their structures were elucidated to be euchrenone b10(1),senegalensin(2),erythrinin C(3),scandenone(4),osajin(5),alpinum isoflavone(6),isoerysenegalensein E(7),erysenegalensein E(8),diprenylgenistein(9),abyssinone V(10),abyssinone V 4′-methyl ether(11),4′,7-dihydroxyflavanone(12),3′,5,7-trihydroxy-4′-methoxyisoflavone(13),2′,4′,5,7-tetrahydroxyisoflavone(14),genistein(15),daidzein(16),and apigenin(17).Except for compounds 1,4-7,and 9-10,other compounds were isolated from E.variegata for the first time.
基金Supported by The Veterans Health Administration Research Career Development Award (DEK)
文摘AIM: To compare hepatitis C virus (HCV) titers in patients with chronic hepatitis C with and without exposure to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).METHODS: Medical records were reviewed for 6463 patients with documented HCV infection at a single center between March 2004 and September 2006. Patients with confi rmed viremia and meeting inclusion criteria were assigned to one of three groups: Group A (n = 50), dyslipidemic patients with statin usage during HCV RNA polymerase chain reaction (PCR) determination; Group B (n = 49), dyslipidemic patients with prior or future statin usage but not at the time of HCV RNA PCR determination; and Group C (n = 102), patients without statin usage during the study period. The primary analysis explored the effect of statin therapy on HCV viremia. Secondary analyses assessed class effect, dose response, and effect of other lipid-lowering therapies on HCV viral titers.RESULTS: Median HCV RNA titers did not signif icantly differ among the three groups (Group A: 4 550 000 IU/mL, Group B: 2 850 000 IU/mL, Group C: 3 055 000 IU/mL).For those subjects with longitudinal assessment of HCV viremia prior to and while on statins, there were no signif icant differences between pre- and post-HCV viral titers. Additionally, no differences in HCV titers were observed at any dose level of the most prescribed statin, simvastatin. However, hypertriglyceridemia independently correlated with HCV titers, and niacin exposure was associated with signif icantly lower viral titers (P < 0.05).CONCLUSION: There was no apparent effect of statins on HCV viral replication in this analysis. Further investigation is warranted to explore the possible antiviral properties of triglyceride-lowering agents and their potential role as adjuncts to standard HCV therapy.
基金Supported by the Science & Technology Planning Project of Hunan Province,China (No.2011FJ3214)
文摘Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.
基金supported by the Science Technology and Innovation Committee of Shenzhen Municipality of China(Grant Nos.JCYJ20170303154319837 and JCYJ20170412155447658)the Science Technology Innovation and Industrial Development of Dapeng New District,Shenzhen,China(Grant Nos.PT201901-18 and PT201901-20).
文摘Protein prenylation plays a crucial role in plant development and stress response.We report the function of pren yltra nsferase a-sub unit in rice.Protein-protei n in teractions showed that the fam esyl-transferase(OsPFT)/geranylgeranyltransferase-l(OsPGGT l-a)protein interacted together with OsPFT-P and OsPGGT l-p.The a-and p-subunits of OsPFT formed a heterodimer for the transfer of a farnesyl group from famesyl pyrophosphate to the CaaX-box-containing peptide N-dansyl-GCVLS.Furthermore,the tissue expressi on patter ns of the OsPFT and OsPGGT I sub units were similar,and these sub units were localized in the cytoplasm and nucleus.Moreover,OsPFT/OsPGGT/-a-deletion homozygous rice mutants had a lethal phenotype,and the heterozygous mutants exhibited reduced pollen viability.These results indicated that prenylation plays an important role in rice development.
基金National Natural Science Foundation of China(Grant Nos.21572277,81573317 and 81703369)CAMS Innovation Fund for Medical Sciences(CIFMS-2016-I2M-3-012)
文摘C-glycosylation and C-prenylation are two important C-C-bond forming reactions for preparation,diversification and structural modification of natural/unnatural products with pharmacological activities.Here,we described unprecedented enzymatic cascades to C-glycosylate/prenylate different acyl resorcinol derivatives in stepwise,one-pot reactions by combining two promiscuous enzymes,MiCGT,a C-glycosyltransferase,and AtaPT,a prenyltransferase.Five novel bis-C-alkylated products were obtained and structurally identified by MS and NMR spectroscopic data as well as comparison with the literature.This study provided a potential synthetic strategy for synthesizing structurally novel and diverse compounds bearing both C-glycosyl and C-prenyl moieties by a two-step,enzymatic bis-C-alkylation.
基金National Natural Science Foundation of China(Grant No.81472657 and 81272468)
文摘Prenylated flavonoids are mainly distributed in Leguminosae and Moraceae plants, and they have been reported to possess various biological activities. Previously, we have reported a prenylated isoflavonoid, isoangustone A（IAA） from licorice（Glycyrrhiza uralensis）, which induces apoptosis in colorectal cancer cells by disrupting mitochondrial functions. In the present study, we compared a group of flavonoids from licorice with IAA for their anti-proliferation activities and effects on intracellular signaling. The results indicated that the isoprenyl groups on the A and B rings, the hydroxyl groups at the ortho position of isoprenyl on A ring and the conjugated plane of C ring might contribute to the anti-cancer activity of prenylated flavonoids. Based on the above structure-activity relationship, we further identified four prenylated flavonoids with similar anti-cancer activities from licorice. Taken together, our present study established a preliminary structure-activity relationship of anti-cancer prenylated flavonoids, and our data provided important leading compounds from licorice, which deserved further research and development.
基金supported by Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine(No.2010JZ-W-01)Ministry of Education,PRC,and National Key Technology R&D Program“New Drug Innovation”of China(Nos.2009ZX09308-004,2013ZX09103002-006)
文摘Four prenylated flavonoids compounds 1-4,named sinopodophyllines A-D,and a flavonoid glycoside(compound 13),sinopodophylliside A,together with 19 known compounds(compounds 5-12 and 14-24) were isolated from the fruits of Sinopodophyllum hexandrum.The structures of new compounds were elucidated by extensive spectroscopic analysis,including HRESIMS,1D and 2D NMR.Compounds 1-6,9-11,and 14-17 were tested for their cytotoxicity against human breast-cancer T47 D,MCF-7 and MDA-MB-231 cells in vitro,and compounds 2,5,6,10 and 11 showed significant cytotoxicity(IC50 values < 10 μmol·L^(-1))against T47 D cells.
基金supported by the National Science and Technology Major Project(No.2017ZX09301072)China Postdoctoral Science Foundation(No.2016M603041).
文摘Six new prenylated flavonoid glycosides,including four new furan-flavonoid glycosides wushepimedoside A–D(1–4)and two new prenyl flavonoid derivatives wushepimedoside E–F(5–6),and one know analog epimedkoreside B(7)were isolated from biotransformation products of the aerial parts of Epimedium wushanense.Their structures were elucidated according to comprehensive analysis of HR-MS and NMR spectroscopic data,and the absolute configurations were assigned using experimental and calculated electronic circular dichroism(ECD)data.The regulatory activity of compounds 1–7 on the production of testosterone in primary rat Leydig cells were investigated,and 4 and 5 exhibited testosterone production-promoting activities.Molecular docking analysis suggested that bioactive compounds 4 and 5 showed the stable binding with 3β-HSD and 4 also had good affinity with Cyp17A1,which suggested that these compounds may regulate testosterone production through stimulating the expression of the above two key proteins.
文摘In continuation of our chemical investigation on some medicinal plants of the genus Tephrosia, re-investigation of the methylenechloride/methanol （1：1） extract of the air-dried aerial part of Tephrosia apollinea afforded a new prenylated flavonoid 1, in addition to an aromatic ester, a sesquiterpene, a lignan and several known prenylated flavonoids. The structures were established by （^1H NMR, ^13C NMR, DEPT, ^1H-^1H COSY, HMQC, HMBC, NOESY and HRMS）. Relative configurations of 9 and 10 were confirmed by X-ray analysis.
文摘A new prenylated flavonol, maackiaflavonol, was isolated from the ethanol extract of the roots of Maackia tenuifolia. Its structure was elucidated as 7-hydrox-8-prenylflavonol by means of spectroscopic analysis (UV, IR, MS, NMR and 1H-1H COSY) and confirmed by total synthesis.
文摘Three new compounds named (2E)prenyl benzoate-4-O-α-L-arabinopyranosyl (1→6) β-D-glucopyranoside (1), 7-methoxy-8-O-β-D-glucopyranosyl coumarin (2), and 3,4'-dihydroxy-3'-methoxy benzenepentanoic acid (3) were isolated from the leaves of Acanthopanax senticosus Harms. The structures of new compounds were determined by means of 2D NMR experiments and chemical methods.
基金supported by the Great Research Project of National Major New Drug Development(No. 2009ZX09102-110)
文摘2-[3,5-Di-O-β-D-glucosyl-4-(3-methylbut-2-enyl)phenyl]benzofuran-6-ol,a new prenylated arylbenzofuran derivative was isolated from Morus alba L.Its structure was elucidated by various spectroscopic methods including MS,~1H NMR,^(13)C NMR,DEPT,~1H-~1HCOSY,HMQC and HMBC.
文摘Two new dihydroflavonoids were obtained from the traditional Chinese medicinal herb Patrinia villosa Juss. Their structures were elucidated as （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6, 8-di （γ, γ-dimethylallyl） flavanone （1） and （2S）-5, 7, 2＇, 6＇-tetrahydroxy-6-1avandulylated flavanone （2） by spectroscopic methods including UV, IR, HR-TOF-MS, 1D NMR and 2D NMR techniques.
基金supported by the National Natural Science Foundation of China(No.22177016)the Natural Science Foundation of Chongqing(No.cstc2020jcyj-msxmX0537)the Open Project of State Key Laboratory of Natural Medicines(No.SKLNMKF202011).
文摘Five new flavonoid derivatives,cajavolubones A-E(1-5),along with six known analogues(6-11)were isolated from Cajanus volubilis,and their structures were elucidated by spectroscopic analysis and quantum chemical calculations.Cajavolubones A and B(1 and 2)were identified as two geranylated chalcones.Cajavolubone C(3)was a prenylated flavone,while cajavolubones D and E(4 and 5)were two prenylated isoflavanones.Compounds 3,8,9 and 11 displayed cytotoxicity against HCT-116 cancer cell line.
基金financially supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. NRF-2009-0094071), South Korea
文摘An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.
