Chemical approaches for the stereocontrolled synthesis of 1,2-cis-β-D-rhamnosides / 中国天然药物

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-β-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain β-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of β-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in β-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.

Meroterpenoids from Rhododendron nivale / 中国中药杂志

To elucidate the chemical material basis of Rhododendron nivale, this study comprehensively used various chromatographic techniques to isolate and obtain five new meroterpenoid enantiomers(1a/1b-5a/5b) from the ethyl acetate extract of R. nivale. A variety of spectral analytical methods, such as high-resolution mass spectrometry(HRMS), nuclear magnetic resonance spectroscopy(NMR), and infrared(IR) spectrum, were used to evaluate the structure, combined with the measurement and calculation of electronic circular dichroism(ECD). The new compounds 1a/1b-4a/4b were named as(±)-nivalones A-B(1a/1b-2a/2b) and(±)-nivalnoids C-D(3a/3b-4a/4b), along with one known enantiomer(±)-anthoponoid G(5a/5b). Human neuroblastoma cells(SH-SY5Y cells) induced by hydrogen peroxide(H_2O_2) were used as oxidative stress models to evaluate the protective activity of the isolated compounds against oxidative damage to nerve cells. It was found that compounds 2a and 3a had a certain protective effect on nerve cells against H_2O_2-induced oxidative damage at concentrations of 50 μmol·L~(-1), which increased the cell survival rate from 44.02%±2.30% to 67.82%±1.12% and 62.20%±1.87%, respectively. Other compounds did not show a significant ability to protect cells from oxidative damage. These findings enrich the chemical constituents of R. nivale and provide valuable information for identifying the structure of its meroterpenoids.

Bioactive neolignans and lignans from the roots of Paeonia lactiflora / 中国天然药物

Two new neolignans and one new lignan (1-3) were obtained from the roots of Paeonia lactiflora. Their structures were unambiguously elucidated based on extensive spectroscopic analysis, single-crystal X-ray crystallography, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1 was a racemic mixture and successfully resolved into the anticipated enantiomers via chiral-phase HPLC. Compound 3 demonstrated moderate inhibitory activity against human carboxylesterase 2A1 (hCES2A1) with an IC50 value of 7.28 ± 0.94 μmol·-1.

Chemical constituents of sesquiterpenes from Chloranthus multistachys / 中国中药杂志

With repeated silica gel, octadecyl silica(ODS), and Sephadex LH-20 column chromatography, normal-phase and reverse-phase high performance liquid chromatography(HPLC), etc., a pair of new enantiomers and 5 known compounds were separated from the 95% ethanol extract of Chloranthus multistachys. These compounds were identified by the nuclear magnetic resonance spectroscopy(including 1 D-NMR and 2 D-NMR), single-crystal X-ray diffraction, circular dichroism(CD) spectroscopy, mass spectrometry(MS), and some other methods as(1R,4R,5R,8S,10R)-chloraeudolide H(1 a),(1S,4S,5S,8R,10S)-chloraeudolide H(1 b), hydroxyisogermafurenolide(2), 4α-hydroxy-5α,8β(H)-eudesm-7(11)-en-8,12-olide(3), chloraniolide A(4), chlorantene D(5), 4α,8β-dihydroxy-5α(H)-eudesm-7(11)-en-8,12-olide(6). Compounds 1 a and 1 b are a pair of new eudesmane-type sesquiterpene enantiomers, and compounds 2-4 were isolated from C. multistachys for the first time.

Isolation of Penicillium expansum WH-3 for the production of L(+)-tartaric acid / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The L(+)-form of tartaric acid (L(+)-TA) exists extensively in nature, and is widely used in the food, chemical, textile, building, and pharmaceutical industries (Su et al., 2001). The main method for L(+)-TA production is microbial transformation by cis-epoxysuccinate hydrolase (CESH), which can catalyze the asymmetric hydrolysis of cis-epoxysuccinic acid or its salts to TA or tartrate (Bao et al., 2019). Seventeen species containing CESH have been isolated so far. However, most species for L(+)-TA production have been reported from bacteria (Xuan and Feng, 2019). The only fungus isolated from soil by our lab recently, that could be used as catalyst for the process under acidic condition, is Aspergillus niger WH-2 (Bao et al., 2020). In order to find strains with new characteristics, this study attempted to isolate a new CESH source from fungi and investigate its application value.

Research Progress on Chiral Separation Methods and Toxic Effects of Methamphetamine Enantiomers / 法医学杂志

Methamphetamine （MAMP） is a kind of amphetamine-type stimulants （ATS） which contains one chiral carbon atom in its structure. Therefore a pair of enantiomers, S-（+）-MAMP and R-（-）-MAMP exist. R type and S type methamphetamines possess similar physicochemical properties, but has largely different pharmacological and toxic effects. S-（+）-MAMP is the main component of addictive drug "Ice" at present, seriously affecting human health and public safety. The separation analysis and mechanism of toxic effects discussions on MAMP are the current research focuses. This paper reviews the research progress of separation analysis methods and toxic effects of methamphetamine enantiomers to provide reference for forensic study and forensic practice.

A pair of cyclopeptide epimers from the seeds of Celosia argentea / 中国天然药物

Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.

A pair of cyclopeptide epimers from the seeds of Celosia argentea / 中国天然药物

Two cyclopeptides, celogentin L (1) and its epimer lyciumin A (2) were firstly isolated from Celosia argentea L.. The planar structures of the two compounds were fully determined by spectroscopic data, including 1D-, 2D-NMR, and HR-ESI/MS. The absolute configurations of amino acid components were assigned via chiral-phase HPLC analyses after acid hydrolysis. Furthermore, the configuration of C-N linkage at the glycine Cα was elucidated by extensive analyses of 2D-NMR and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cytotoxicity of the two compounds against human alveolar epithelial A549, hepatocellular carcinoma HepG2, and cervical cancer Hela cell lines was assayed. Although both of them were inactive in these cells, the present findings add new facets for the chemistry of Celosia argentea.

S-(+)- and R-(-)-linalool: a comparison of the in vitro anti-Aeromonas hydrophila activity and anesthetic properties in fish

ABSTRACT Linalool is the main compound of many essential oils and occurs in two isomeric forms: S-(+)- and R-(-)-linalool. This study aimed to determine if linalool isomers have different antimicrobial and anesthetic properties in fish. For this purpose, these compounds were previously isolated from Lippia alba (Mill.)N. E. Brown and Ocimum americanum L. essential oils. Antimicrobial effects were evaluated through the microdilution test against Aeromonas hydrophila, an important fish disease etiologic agent. Induction time until sedation, anesthesia and recovery time were determined in silver catfish (Rhamdia quelen) through bath exposure (60, 180, 300 or 500 μL L-1). The results showed different biological properties for the isomers being S-(+)-linalool the only active against A. hydrophila at 3.2 mg mL-1. The sedation was induced without differences between the compounds, however R-(-)-linalool promoted faster anesthesia. There were no differences regarding the recovery time of the animals exposed to the linalool isomers. Although both S-(+)- and R-(-)-linalool can be used for sedative purposes, their use in A. hydrophila infection is inadvisable due to the high effective concentration. Considering anesthesia as the main objective, the R-(-)-linalool demonstrated clear advantages at lower concentration.

7-epi-griffonilide, a new lactone from Bauhinia pentandra: complete 1H and 13C chemical shift assignments

ABSTRACT A new lactone, 7-epi-griffonilide (1), and six known compounds, 2, 3a - 3c, 4a and 4b, were isolated from the leaves of Bauhinia pentandra (Fabaceae). The structures elucidation of 1 and 2 were based on detailed 2D NMR techniques and spectral comparison with related compounds, leading to complete assignment of the 1H and 13C NMR spectra.

A New Stereoisomeric Monoterpene Glycoside from Clematis heracleifolia leaves

A new stereoisomeric monoterpene glycoside and five already-known compounds were isolated from the n-BuOH soluble fraction of Clematis heracleifolia leaves. On the basis of spectral data, the structures of the isolated compounds were identified as protocatechuic acid (1), ferulic acid (2), caffeic acid (3), aesculin (4), (6Z)-9-hydroxylinaloyl glucoside (5), and 9-hydroxylinaloyl glucoside (6) and these were isolated for the first time from this plant. Among these compounds, (6Z)-9-hydroxylinaloyl glucoside (5) is a newly isolated from plant source.

Regio- and stereo-selective hydroxylations of ingenane diterpenoids by Mortierella ramanniana and Gibberella fujikuroi / 中国天然药物

The regio- and stereo-selective hydroxylations of two ingenane diterpenoids, 20-deoxyingenol (1) and 13-oxyingenol dodecanoat (2), by the filamentous fungi Mortierella ramanniana and Gibberella fujikuroi were investigated in the present study. Four undescribed metabolites (3-6) of substrate 1 and two undescribed metabolites (7 and 8) of substrate 2 were isolated. All the metabolites were identified as hydroxylated ingenane derivatives by extensive NMR and HR-ESI-MS data analyses. All the biotransformed compounds and the substrates were evaluated for their cytotoxicities against three human cancer cell lines, including human colon cancer Caco-2, breast cancer MCF-7, and adriamycin (ADM)-resistant MCF-7/ADM cell lines. All ingenane alcohols (1, and 3-6) displayed no significant cytotoxic activities. The substrate 13-oxyingenol dodecanoat (2) showed moderate cytotoxicity with IC values being 35.59 ± 5.37 μmol·L (Caco-2), 24.04 ± 4.70 μmol·L (MCF-7), and 22.24 ± 5.19 μmol·L (MCF-7/ADM). However, metabolites 7 and 8 displayed no significant cytotoxicity. These results indicated that the hydroxylation at the C-13 aliphatic acid ester of substrate 2 can significantly reduce the cytotoxic activity.

Effect of Ginsenoside Rg2 and Its Stereoisomers on Oxygen-Glucose Deprivation and Reperfusion Induced Cortical Neuronal Injury Model / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of natural type ginsenoside Rg2 (Rg2) and its stereoisomers [20 (R)-Rg2 and 20 (S)-Rg2] at different concentrations on oxygen-glucose deprivation/ reperfusion (OGD/R) induced cortical neuronal injury model in vitro, and to explore the mechanism, and compare their differences of action.</p><p><b>METHODS</b>Cortical neurons after 7-day culture were randomly divided into 5 groups, i.e., the control group, the model group, the Rg2 group, 20 (R) -Rg2 group, and 20 (S) - Rg2 group. Cortical neurons in the Rg2 group, 20 (R)-Rg2 group, and 20(S)-Rg2 group were pretreated with 20, 40, and 80 μmol/L Rg2, 20 (R) -Rg2, and 20 (S) -Rg2 for 24 h to prepare OGD/R model. The cell survival rate, the activity of Caspase-3, the intracellular Ca2+ concentration, contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected 24 h later.</p><p><b>RESULTS</b>Compared with the control group, cell survival rates and activities of SOD obviously decreased, the activity of Caspase-3, Ca2+ fluorescent optical gray value, and contents of MDA significantly increased with statistical difference (P < 0.05). Compared with the model group, cell survival rates and activities of SOD obviously increased, the activity of Caspase-3, Ca2+ fluorescent optical gray value, and contents of MDA significantly decreased in 20 μmol/L Rg2 group, 40 μmol/L 20 (R) -Rg2 group, and 80 μmol/L 20 (S) -Rg2 group (P < 0.05). Compared with 20(S)-Rg2 group, cell survival rates increased and contents of MDA significantly decreased in 20, 40, and 80 μmol/L Rg2 and 20 (R)-Rg2 groups (P < 0.05). The activity of Caspase-3 decreased and contents of SOD increased in 80 μmol/L 20 (R)-Rg2 group, and 40, 80 μmol/L Rg2 groups (P < 0.05). Ca2+ fluorescent optical gray value decreased in 40, 80 μmol/L Rg2 and 20 (R)-Rg2 groups (P < 0.05). Compared with 20 (R)-Rg2 group, Ca2+ fluorescent optical gray value decreased in 80 μmol/L Rg2 group (P < 0.05); contents of SOD increased in 40 and 80 μmol/L Rg2 groups (P < 0.05); contents of MDA decreased in 20, 40, and 80 μmol/L Rg2 groups (P < 0.05).</p><p><b>CONCLUSIONS</b>Rg2 and its stereoisomers could improve cell vitality of cortical neurons against OGD/R induced injury. This might be related to improving anti-apoptotic capacities and antioxidant abilities, and reducing Ca2+ inflow. Besides, the neuroprotective effect of 20 (R) -Rg2 was better than that of 20 (S) -Rg2, but inferior to that of Rg2.</p>

Enhancing Effect of Chiral Enhancer Linalool on Skin Permeation of Naproxen / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the permeation-enhancing effect of dl-linalool, d-linalool, and l-linalool on model drugs across excised rat skin and the effect of linalool on the ceramides in stratum corneum lipids.</p><p><b>METHODS</b>In vitro skin permeation studies were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by high performance liquid chromatography with chiral stationary phase. Infrared spectroscopy was used to investigate the effect of linalool on stratum corneum lipids.</p><p><b>RESULTS</b>When the donor vehicles added with 1% dl-linalool, 1% d-linalool, or 1% l-linalool, the steady-state skin permeation rate of naproxen was (2.47±0.63), (1.53±0.54), (1.73±0.48) μg·cm(-2)·h(-1), respectively, which is 2.49, 1.55, and 1.75 times (all P<0.05) compared with control group [(0.99±0.42)μg·cm(-2)·h(-1)], and the differences were statistically significant (all P<0.05). The permeation-enhancing effect of dl-linalool on naproxen was found significantly greater than that of d-linalool and l-linalool (both P<0.05). Compared with the control group, the stratum corneum treated with dl-linalool shifted to higher wave number on 2.09 cm(-1) of asymmetric CH2 stretching vibrations in attenuated total reflection-fourier transform infrared spectroscopy analysis. However, stratum corneum treated with d-linalool and l-linalool did not display this phenomenon.</p><p><b>CONCLUSION</b>The disturbing degree of dl-linalool on stratum corneum lipids (ceramides) is different from that of linalool enantiomers, suggesting their different enhancing effect on the same drug.</p>

Myocardial contractility impairment with racemic bupivacaine, non-racemic bupivacaine and ropivacaine. A comparative study

PURPOSE: To study racemic bupivacaine, non-racemic bupivacaine and ropivacaine on myocardial contractility. METHODS: Isolated Wistar papillary muscles were submitted to 50 and 100 mM racemic bupivacaine (B50 and B100), non-racemic bupivacaine (NR50 and NR100) and ropivacaine (R50 and R100) intoxication. Isometric contraction data were obtained in basal condition (0.2 Hz), after increasing the frequency of stimulation to 1.0 Hz and after 5, 10 and 15 min of local anesthetic intoxication. Data were analyzed as relative changes of variation. RESULTS: Developed tension was higher with R100 than B100 at D1 (4.3 ± 41.1 vs -57.9 ± 48.1). Resting tension was altered with B50 (-10.6 ± 23.8 vs -4.7 ± 5.0) and R50 (-14.0 ± 20.5 vs -0.5 ± 7.1) between D1 and D3. Maximum rate of tension development was lower with B100 (-56.6 ± 38.0) than R50 (-6.3 ± 37.9) and R100 (-1.9 ± 37.2) in D1. B50, B100 and NR100 modified the maximum rate of tension decline from D1 through D2. Time to peak tension was changed with NR50 between D1 and D2. CONCLUSIONS: Racemic bupivacaine depressed myocardial contractile force more than non-racemic bupivacaine and ropivacaine. Non-racemic and racemic bupivacaine caused myocardial relaxation impairment more than ropivacaine. .

Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

Historical review of clinical vaccine studies at Oswaldo Cruz Institute and Oswaldo Cruz Foundation - technological development issues

This paper presents, from the perspective of technological development and production, the results of an investigation examining 61 clinical studies with vaccines conducted in Brazil between 1938-2013, with the participation of the Oswaldo Cruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies have been identified and reviewed according to criteria, such as the kind of vaccine (viral, bacterial, parasitic), their rationale, design and methodological strategies. The results indicate that IOC and Fiocruz have accumulated along this time significant knowledge and experience for the performance of studies in all clinical phases and are prepared for the development of new vaccines products and processes. We recommend national policy strategies to overcome existing regulatory and financing constraints.

Associação entre fatores de risco cardiovascular e indicadores antropométricos de obesidade em universitários de São Luís, Maranhão, Brasil / The association between cardiovascular risk factors and anthropometric obesity indicators in university students in São Luís in the State of Maranhão, Brazil

O presente artigo tem por objetivo avaliar associação entre fatores de risco cardiovascular (FRCV) e indicadores antropométricos em amostra de base populacional de universitários de São Luís/MA. Estudo transversal com 968 universitários, mediana de 22 anos. Glicemia, triglicerídeos (TGL), HDL-c, tabagismo, consumo de álcool, sedentarismo, síndrome metabólica (SM–critérios do Joint Interim Statement) e resistência insulínica (RI), foram associados e correlacionados com os indicadores antropométricos Índice de Massa Corporal (IMC), Circunferência da Cintura (CC), Relação Cintura Quadril (RCQ) e Relação Cintura Altura (RCA). Encontraram-se associações entre TGL, HAS, SM e maiores valores de todas as variáveis antropométricas. RI associou-se a maiores valores IMC e RCA em homens e mulheres. Baixo HDL-c foi associado a maiores valores de todas as variáveis antropométricas em mulheres. Consumo de álcool associou-se a valores mais elevados de IMC e CC em mulheres e RCQ e RCA em homens. Fumo associou-se a maiores valores de RCA em ambos os sexos. Sedentarismo foi associado a maiores valores de RCQ apenas em homens. As correlações mais altas foram estabelecidas para mulheres entre TGL e IMC, CC, RCQ e RCA. Os indicadores que mais se associaram aos FRCV foram IMC, CC e RCA em mulheres e RCQ e RCA em homens.

The article aims to evaluate the relation between cardiovascular risk factors (CVRF) and anthropometric indicators in a sample of university students from São Luís-MA, Brazil. It is a cross-sectional study conducted with 968 university students, with median age of 22. Glycemia, triglycerides, HDL-c, smoking, alcohol consumption, physical inactivity, metabolic syndrome (Joint Interim Statement criteria) and insulin resistance (IR), were associated and correlated with anthropometric indicators such as BMI, WC, WHR and WHtR. Associations were found between TGL, SH, SM and higher values of all anthropometric variables. The RI was associated with higher BMI values and WHtR in men and women. The low HDL-c was associated with higher values of all anthropometric variables in women. Consumption of alcohol was associated with higher values of BMI and WC in women and WHR in men and WHtR. Smoking was associated with higher values of WHtR in both sexes. Physical inactivity was associated with higher values of WHR in men only. The highest correlations were established for women between TGL and BMI CC, WHR and WHtR. The indicators most associated with CVRF were BMI, WC and WHtR in females and WHR and WHtR in men.

The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration / 药学学报

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

A high-performance liquid chromatography with circular dichroism detector for determination of stereochemistry of 6, 9-oxygen bridge dibenzocyclooctadiene lignans from kadsura coccinea / 中国天然药物

The stereochemistry of two 6, 9-oxygen bridge dibenzocyclooctadiene lignans from Kadsura coccinea, are difficult to separate and very unstable. The present study was designed to develop a high-performance liquid chromatography using circular dichroism detection for the analysis of the stereochemistry. A new 6, 9-oxygen bridge dibenzocyclooctadiene lignans named Kadsulignan Q was firstly found with an S-biphenyl configuration. The other compound was identified as Kadsulignan L with an R- biphenyl configuration. In order to obtain kinetic data on their reversible interconversion, the stability was measured at different deuterated solvents such as deuterated methanol, deuterated chloroform and deuterated dimethylsulfoxide. The lignans were more unstable and converted more easily in deuterated methanol than in deuterated chloroform and deuterated dimethylsulfoxide.