Reaction of the Phytochemistry Community to Green Chemistry: Insights Obtained Since 1990.

This review article aims to study how phytochemists have reacted to green chemistry insights since 1990, the year when the U.S. Environmental Protection Agency launched the "Pollution Prevention Act". For each year in the period 1990 to 2019, three highly cited phytochemistry papers that provided enough information about the experimental procedures utilized were sampled. The "greenness" of these procedures was assessed, particularly for the use of solvents. The highly hazardous diethyl ether, benzene, and carbon tetrachloride did not appear in the papers sampled after 2010. Advances in terms of sustainability were observed mainly in the extraction stage. Similar progress was not observed in purification procedures, where chloroform, dichloromethane, and hexane regularly have been employed. Since replacing such solvents in purification procedures should be a major goal, potential alternative approaches are discussed. Moreover, some current initiatives toward a more sustainable phytochemical research considering aspects other than only solvents are highlighted. Although some advances have been achieved, it is believed that natural products chemists can play a major role in developing a novel ecological paradigm in chemistry. To contribute to this objective, six principles for performing natural products chemistry consistent with the guidelines of green chemistry are proposed.

Antistaphylococcal Prenylated Acylphoroglucinol and Xanthones from Kielmeyera variabilis.

Bioactivity-guided fractionation of the EtOH extract of the branches of Kielmeyera variabilis led to the isolation of a new acylphoroglucinol (1), which was active against all the MRSA strains tested herein, with pronounced activity against strain EMRSA-16. Compound 1 displayed an MIC of 0.5 mg/L as compared with an MIC of 128 mg/L for the control antibiotic norfloxacin. The structure of the new compound was elucidated by 1D and 2D NMR spectroscopic analysis and mass spectrometry, and experimental and calculated ECD were used to determine the absolute configurations. The compounds ß-sitosterol (2), stigmasterol (3), ergost-5-en-3-ol (4), and osajaxanthone (5) also occurred in the n-hexane fraction. The EtOAc fraction contained nine known xanthones: 3,6-dihydroxy-1,4,8-trimethoxyxanthone (6), 3,5-dihydroxy-4-methoxyxanthone (7), 3,4-dihydroxy-6,8-dimethoxyxanthone (8), 3,4-dihydroxy-2-methoxyxanthone (9), 5-hydroxy-1,3-dimethoxyxanthone (10), 4-hydroxy-2,3-dimethoxyxanthone (11), kielcorin (12), 3-hydroxy-2-methoxyxanthone (13), and 2-hydroxy-1-methoxyxanthone (14), which showed moderate to low activity against the tested MRSA strains.

NMR-based metabolomics: a probe to utilize biodiversity.

Metabolomics is a comprehensive profiling tool used to identify qualitatively and quantitatively all the metabolites present in a biological system. As the number of metabolites in a living being is assumed to be around 30,000, it is necessary to use an adequate extraction procedure and a good analytical technique to perform metabolomic analyses. Each analytical platform used in metabolomics has both advantages and disadvantages in terms of the sensitivity and resolution for metabolites to be detected. Of the methods, nuclear magnetic resonance (NMR) spectroscopy has been proved to have several advantages over other MS-based methods. NMR provides an efficient, robust, and nondestructive metabolomics analysis of crude extracts or samples as well as easy quantitation without calibration curves for each metabolite, although it shows relatively low sensitivity than MS-based methods. Thus, NMR-based metabolomics have been often used for the first step to capture the insight of the metabolome of organisms. This chapter presents general steps of NMR-based metabolomic analysis involved in the study of biodiversity.

A comparison on the metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca four years later.

ETHNOPHARMACOLOGICAL RELEVANCE: Galphimia glauca has a long traditional use, and continues to be used in Mexico as a natural tranquilizer for the treatment of Central Nervous System disorders as well as for other illnesses. AIM OF THE STUDY: In 2005 the initial use of metabolic profiling to populations of Galphimia glauca resulted in two of the six collected populations being producers for galphimines, the markers for sedative and anxiolytic activities. The aim of this investigation was to confirm the previously established metabolic profile, as well as the previous in vivo results on mice. Additionally in this study we wanted to investigate potential anti-inflammatory properties. MATERIALS AND METHODS: Four years later, we collected samples in the five localities designated for the first-stage investigation in 2005, and in two new locations. Metabolic profiling was carried out by means of (1)H NMR spectroscopy and multivariate data analysis applied to crude extracts from wild plant specimens. HPLC analysis was performed to confirm and quantify the presence of galphimines. Two neuropharmacological in vivo assays on mice were employed to study anxiolytic (elevated plus maze test) and sedative (sodium pentobarbital-induced hypnosis model) activities in the extracts. Anti-inflammatory activity was determined by using the tetradecanoylphorbol acetate-induced mouse ear inflammation model (TPA). RESULTS AND CONCLUSIONS: The results for the 2009 collected species were similar to the 2005 collection, confirming the metabolic profiles and that galphimines are consistent good markers for CNS activity. Galloylquinic acid levels varied between the years without, as of yet, known effects. In vivo anti-inflammatory activity was similar for all plants and thus not linked with galphimines, requiring further studies to identify the active compound(s). Areas of collection affect neuropharmacological activities but not anti-inflammatory action.

In silicio expression analysis of PKS genes isolated from Cannabis sativa L.

Cannabinoids, flavonoids, and stilbenoids have been identified in the annual dioecious plant Cannabis sativa L. Of these, the cannabinoids are the best known group of this plant's natural products. Polyketide synthases (PKSs) are responsible for the biosynthesis of diverse secondary metabolites, including flavonoids and stilbenoids. Biosynthetically, the cannabinoids are polyketide substituted with terpenoid moiety. Using an RT-PCR homology search, PKS cDNAs were isolated from cannabis plants. The deduced amino acid sequences showed 51%-73% identity to other CHS/STS type sequences of the PKS family. Further, phylogenetic analysis revealed that these PKS cDNAs grouped with other non-chalcone-producing PKSs. Homology modeling analysis of these cannabis PKSs predicts a 3D overall fold, similar to alfalfa CHS2, with small steric differences on the residues that shape the active site of the cannabis PKSs.

In silicio expression analysis of PKS genes isolated from Cannabis sativa L.

Cannabinoids, flavonoids, and stilbenoids have been identified in the annual dioecious plant Cannabis sativa L. Of these, the cannabinoids are the best known group of this plant's natural products. Polyketide synthases (PKSs) are responsible for the biosynthesis of diverse secondary metabolites, including flavonoids and stilbenoids. Biosynthetically, the cannabinoids are polyketide substituted with terpenoid moiety. Using an RT-PCR homology search, PKS cDNAs were isolated from cannabis plants. The deduced amino acid sequences showed 51 percent-73 percent identity to other CHS/STS type sequences of the PKS family. Further, phylogenetic analysis revealed that these PKS cDNAs grouped with other non-chalcone-producing PKSs. Homology modeling analysis of these cannabis PKSs predicts a 3D overall fold, similar to alfalfa CHS2, with small steric differences on the residues that shape the active site of the cannabis PKSs.

Metabolic profiling of the Mexican anxiolytic and sedative plant Galphimia glauca using nuclear magnetic resonance spectroscopy and multivariate data analysis.

Galphimia glauca is popularly employed in Mexico for the treatment of central nervous system disorders. Pharmacological and phytochemical studies have resulted in the identification of the anxiolytic and sedative principle consisting of a mixture of nor-secofriedelanes, named the galphimine series (1 - 9). These active constituents were found in plants collected in the vicinity of a restricted region in Central Mexico, where this species is abundant. A metabolic profiling carried out by means of 1H-NMR spectroscopy and multivariate data analysis was applied to crude extracts from wild plant populations, collected from six different locations as a quality control assessment, in order to differentiate their chemical profile. Principal component analysis (PCA) of the 1H-NMR spectra revealed clear variations among the populations, with two populations out of the six studied manifesting differences, when the principal components PC-1 and PC-2 were analyzed. These two PCs permitted the differentiation of the various sample populations, depending on the presence of galphimines. This information consistently correlated with the corresponding HPLC analysis. The neuropharmacological effects of the crude extracts were evaluated by using ICR mice in the elevated plus maze, as well as the sodium pentobarbital-induced hypnosis models. Both assays demonstrated anxiolytic and sedative responses only among those sample populations which had previously been differentiated by PC-1. Partial least square regression-discriminant analysis (PLS-DA) also confirmed a strong correlation between the observed effects and the metabolic profiles of the plants. The overall results of this study confirm the benefits of using metabolic profiling for the in silico analysis of active principles in medicinal plants.