ABSTRACT
Artemisinin is a sesquiterpene lactone natural product that contains an endoperoxide bond. Artemisinin has various biological activities including antimalarial, anti-tumor, antiviral and anti-fibrotic activity. Owing to the poor pharmacokinetic properties of artemisinin, its derivatives are currently used in clinic and frequently reported in literature. Although numerous derivatives of artemisinin have been reported, no study has been carried out yet to study the effect of substituted groups with different acid-base property on the antimalarial activity. Among these derivatives, the C-10 carbon artemisinin derivatives are often reported, and their corresponding 10β epimer show much better antimalarial activity than 10α epimer with large-sized substitute. However, there is currently no stereoselective synthesis to efficiently prepare the privileged 10β epimer of C-10 carba artemisinin. To address these two scientific questions, we herein first report an optimized method to stereoselectively synthesize the 10β epimer of C-10 carba artemisinin (98∶2 d.r.). Second, we employed the optimized method to synthesize a series of C-10 carba artemisinin derivatives with different acid-base properties. The antimalarial examination indicated that those derivatives with neutral groups or basic group of short chain showed similar antimalarial activity as dihydroartemisinin (DHA). The acidic group could dramatically decrease the antimalarial effect and was more than 22-fold less effective than DHA or the neutral ones. This study will shed light on the development of new generation of artemisinin derivatives with potent activity.
ABSTRACT
Paris polyphylla var. chinensis(PPC) is used as one of the origin plants of Paridis Rhizoma described in the Chinese Pharmacopoeia(2020 edition). Its resources shortage makes the planting scale gradually expand, and plenty of aerial parts are abandoned because of not being effectively used. On the basis of previous research, this study separated steroidal saponins to further clarify the chemical composition of the aerial parts of PPC. As a result, three pairs of 25R or 25S epimers of furostanol saponins were obtained by various column chromatography techniques. Their structures were identified as neosolanigroside Y6(1), solanigroside Y6(2), neoprotogracillin(3), protogracillin(4), neoprotodioscin(5) and protodioscin(6) by spectral data combining with chemical transformation. Compound 1 is a new compound, and compounds 2, 3 and 5 are isolated from Paris plants for the first time. Compounds 4 and 6 are isolated from this plant for the first time. Previously, only several spirostanol glycosides with 25S configuration were isolated from Paris plants. Guided by mass spectrometry, the present study isolated the furostanol saponins with 25S configuration from this genus for the first time, which further enriches the chemical information of Paris genus and provides a reference for the isolation of similar compounds.
Subject(s)
Liliaceae , Melanthiaceae , Plant Extracts , Rhizome , SaponinsABSTRACT
One new and two known dammarane-type saponins were isolated from the leaves of Gynostemma pentaphyllum using various chromatographic methods. Their structures were identified by HR-ESI-MS,~( 1)H-NMR, ~(13)C-NMR, 2 D-NMR spectra as 2α,3β,12β,20,24(S)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(1, a new compound, namely gypenoside J5) and 2α,3β,12β,20,24(R)-tetrahdroxydammar-25-en-3-O-[β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl]-20-O-β-D-xylopyranosyl(1→6)-β-D-glucopyranoside(2) and 2α,3β,12β,20-tetrahydroxy-25-hydroperoxy-dammar-23-en-3-O-[β-D-glucopyranosyl(1→2)][β-D-glucopyranosyl]-20-O-[β-D-xylopyranosyl(1→6)]-β-D-glucopy-ranoside(3), respectively. Compounds 1 and 2 were a pair of C-24 epimers. All compounds showed weak cytotoxicity agxinst H1299, HepG2, PC-3, SH-SY5 Y cancer cell lines. However, they exerted protective effect against SH-SY5 Y cellular damage induced by H_2O_2 dose-dependently, of which compound 1 displayed the strongest antioxidant effect. The present study suggested that G. pentaphyllum has antioxidative potential and the saponins from G. pentaphyllum are considered as the active compounds with neuroprotecitve effect.
Subject(s)
Gynostemma , Molecular Structure , Neuroprotective Agents/pharmacology , Saponins/pharmacology , Triterpenes/pharmacologyABSTRACT
Because many therapeutic agents are contaminated by epimeric impurities or form epimers as a result of metabolism, analytical tools capable of determining epimers are increasingly in demand. This article is a proof-of-principle report of a novel DMS-MS/MS method to separate and simultaneously quantify epimers, taking PGF2 and its 8-epimer, 8--PGF2, as an example. Good accuracy and precision were achieved in the range of 10-500 ng/mL with a run time of only 1.5 min. Isopropanol as organic modifier facilitated a good combination of sensitivity and separation. The method is the first example of the quantitation of epimers without chromatographic separation.
ABSTRACT
Objective: To study the chemical constituents from the medicinal herb of Caesalpinia decapetala. Methods: Silica gel and Sephadex LH-20 column chromatography techniques were used as pretreatments for ethanol extract of the seeds of C. decapetala, and then semi-preparative HPLC technique was used. Results: Eight cassane diterpenes were isolated from the chloroform extract of C. decapetala. According to NMR, ESI-MS, and CD spectrum data, they were identified as 1α,6α,7β-triacetoxy-14α-methoxy- vouacapen-5α-ol (1), caesalmin F (2), neocaaesalpin MP (3), 1-deacteoxy-1-oxocaesalmin C (4), neocaesalpin AA (5), bonducellpin C (6), bonducellpin E (7), and neocaaesalpin N (8). Conclusion: Compound 1 is a new compound and named as caediterpene A, compound 1-2 are a pair of epimeric diterpenes, and compounds 3-7 are obtained for the first time from the seeds of C. decapetala.
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Objective To establish a method for the preparative separation and isolation of the epimeric labdenetriols,phy?sanicantriol(1)and 14-epi-physanicantriol(2),from the leaves of Artemisia argyi.Methods The CH2Cl2fraction of 95% EtOH ex?tract from the leaves of A.argyi was separated by Diaion HP-20,silica gel and Sephadex LH-20 column chromatography and purified by semi-preparative HPLC to obtain an epimeric mixture of 1 and 2.Then,the epimeric mixture was separated by silica gel H column chromatography with eluting by n-hexane-CH2Cl2-isopropyl alcohol(1:1:0.15,V/V/V)to obtain compounds 1 and 2.The structures of 1 and 2 were identified by comparing MS and NMR data with those reported in the literature.Results and Conclusion Two diterpe?noids were isolated for the first time from the family Compositae.This method is effective,convenient and rapid,and is suitable for the separation and preparation of the epimers 1 and 2.
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Objective:To establish an HPLC method for the simultaneous determination of 18α-glycyrrhizic acid and 18β-glycyr-rhizic acid in diammonium glycyrrhizinate .Methods:A Diamonsil C18 column (200 mm ×4.6 mm, 5 μm) was used with the mobile phase of water (water-60%perchloric acid solution:48∶0.5, adjusting pH to 8.0 with ammonium hydroxide)-methanol (48∶52). The detection wavelength was set at 248 nm and the flow rate was 1.0 ml· min-1 .The column temperature was 30℃and the injection volume was 20 μl.Results:18α-Glycyrrhizic acid and 18β-glycyrrhizic acid were well separated .They had a good linear relationship within the range of 0.005 0-1.000 0 mg· ml-1(r=0.999 7 and 0.999 3).The average recovery was 99.7%and 99.1%, and RSD was 0.9%and 0.4%, respectively (n=9).Conclusion:The method is accurate, simple and reproducible, which can be used for the simultaneous determination of the two constituents in diammonium glycyrrhizinate .
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Objective To explore the excretion of the 20 (S)-protopanaxatriol (PPT) and its metabolites ocotillol type epimers (M1 and M2) in urine, feces samples and the excretion of Ml and M2 in bile samples. Methods The concentration of PPT, Ml and M2 in urine, feces samples and the concentration of Ml and M2 in bile samples were determined by the LC-MS/MS methods with or without the hydrolization by β-glucuronidase. Results After intragastric(ig) administration of PPT, the cumulative excretion rate for 72 h of PPT, Ml and M2 in feces were 14.88%, 1.34% and 0.084%, respectively. With the hydrolization by β-glucuronidase, the cumulative excretion rate for 72 h of PPT, Ml and M2 in feces were 14.77%, 1.36% and 0.085%, respectively. However, the epimers and PPT were hardly detected in urine. After ig administration of M1 or M2, the accumulation excretion rate were 4.41% for M1 and 47.2% for M2 in feces, while both epimers were hardly detected in urine. After ig administration of M1 or M2, the 36 h cumulative biliary excretion rate was 3.01% for M1, and only 0.068% for M2. The 36 h cumulative biliary excretion rate of M1 was 8.80% after intravenous administration, while only 1.24% for M2. Conclusion After ig administration of PPT, a small amount of PPT and its metabolites (Ml, M2) are excreted by the feces but little via urine, and there are stereoselectivity differences in biliary excretion between M1 and M2.
ABSTRACT
Objective To explore the excretion of the 20(S)-protopanaxatriol(PPT)and its metabolites ocotillol type epi?mers(M1 and M2)in urine,feces samples and the excretion of M1 and M2 in bile samples. Methods The concentration of PPT,M1 and M2 in urine,feces samples and the concentration of M1 and M2 in bile samples were determined by the LC-MS/MS methods with or without the hydrolization byβ-glucuronidase. Results After intragastric(ig)administration of PPT,the cumulative excretion rate for 72 h of PPT,M1 and M2 in feces were 14.88%,1.34%and 0.084%,respectively. With the hydrolization byβ-glucuronidase,the cumulative excretion rate for 72 h of PPT,M1 and M2 in feces were 14.77%,1.36%and 0.085%,respectively. However,the epimers and PPT were hardly detected in urine. After ig administration of M1 or M2,the accumulation excretion rate were 4.41%for M1 and 47.2%for M2 in feces,while both epimers were hardly detected in urine. After ig administration of M1 or M2,the 36 h cumulative bili?ary excretion rate was 3.01%for M1,and only 0.068%for M2. The 36 h cumulative biliary excretion rate of M1 was 8.80%after intra?venous administration ,while only 1.24%for M2. Conclusion After ig administration of PPT,a small amount of PPT and its metabo?lites(M1,M2)are excreted by the feces but little via urine ,and there are stereoselectivity differences in biliary excretion between M1 and M2.
ABSTRACT
OBJECTIVE: To establish the content determination method for dihydroartemisinin(DHA). METHODS: The high performance liquid chromatography was carried out on a column packed with octadecylsilane bonded silica gel (CAPCELL PAK C18 MG II, 4.6 mm × 100 mm, 3 μm), using a mixture of acetonitrile-water (60:40) as the mobile phase. Dimethylsulfoxide was chosen as the solvent for the DHA bulk drug. The detection wavelength was set at 216 nm and the flow rate was 0.6 mL · min-1. RESULTS: The linear range of DHA calibration curve was 0.50535-50.535 μg (r=0.9999). CONCLUSION: Compared with the method included in ChP, the precision of the established content determination method is improved significantly. It is accurate, reliable, convenient, and has good reproducibility for content determination of DHA.
ABSTRACT
@#Ocotillol(3)and its epimer(4)have been synthesized from 20(S)-protopanaxatriol ［20(S)-PPT］ via two routes, and their formation mechanism has been speculated. Route 1: Compounds 3 and 4 were obtained from 20(S)-PPT by oxidation with m-CPBA at the yield of 44. 1% and 28. 6%, respectively. Route 2: Compounds 3 and 4 were prepared from 20(S)-PPT by acetylation, oxidation and saponification at the yield of 16. 4% and 16. 2%, respectively. The formation mechanism of compounds 3 and 4 is speculated as below: 1)The chemical environments of both sides of C24(25)double bond in 20(S)-PPT are different due to the existence of intramolecular hydrogen bond, which led to the different oxidation ratio of the two sides, and the different yields of compounds 3 and 4. 2)There is not intramolecular hydrogen bond in acetylated 20(S)-PPT, and the chemical environments of both sides of C24(25)double bond are similar, which resulted in almost equal yields of compounds 3 and 4 synthesized through oxidation with m-CPBA, intramolecular SN2 and saponification.
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Objective To study the chemical constituents from Leucas ciliata. Methods Silica gel, RP-18, and Sephadex LH-2O column chromatography techniques were used for separation and purification of the compounds and extensive spectral analysis spectrum were employed for structural elucidation. Results Twelve compounds were isolated from ethanol extract of L. ciliata and identified as tricin (1), crisilineol (2), sitosterol-3-O-glucoside (3), stigmast-5-ene-11-ol- 3-O-β-glucoside (4), 5, 7-dimethoxy-2-methyl-4-chromanone (5), 3', 5', 5, 7-tetramethoxy-4'-O-β-glucoside flavone (6), 5-hydroxy-3', 4'-dimethoxy-7-O-β-glucoside flavone (7), acteoside (8), 3, 4-dihydroxy-β-phenylethoxy-O-ααrabinopyranosyl-(l""- →2")α-Z,-rhamnopyranosyl-(r"-→3") -4"-O-caffeoylβ-D-glucopyranoside (9), 3-hydroxy-4-methoxy-β- phenylethoxy-Oα-Lαrabinopyranosyl-(l""-→6") α-L-rhamnopyranosyl-(r"-→3")4"-O-caffeoyl-β-D- glucopyranoside (10), leucasin A (11A), and leucasin B (11B). Conclusion Compounds 11A and 11B are epimers and new compounds, and the other ten compounds are obtained from the plants of Leucas R. Br. for the first time.
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Object To study the isomers of amygdalin in BUYANG HUANWU TANG and its production Methods Amygdalin was isolated from both peach seeds and BUYANG HUANWU TANG by using various column chromatography Their structures were identified by the various spectral data Results Amygdalin had been isolated from n BuOH fraction of aqueous extract of BUYANG HUANWU TANG and found to be a pair of D , L epimers and their ration was 1∶1 It was also found that the structures and the ration of D , L epimers of amygdalin in decoction of single peach seed were similar to that in BUYANG HUANWU TANG. The peach seed only gave D amygdalin when it was extracted in 95% EtOH at reflux temperature, and D amygdalin cannot be isomerized when it was treated in water at 100 ℃ Conclusion Isomerization of D amygdalin results from interaction between it and other compounds of peach seed in water at high temperature, and has no evident relation to other constituents in BUYANG HUANWU TANG L amygdalin is a new compound generated due to decoction of peach seed