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Shikimic acid: Review of its analytical, isolation, and purification techniques from plant and microbial sources

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Abstract

Shikimic acid properties and its available analytical techniques are discussed. Plants having the highest content of shikimic acid are shown. The existing isolation methods are analyzed and the most optimal approaches to extracting this acid from natural sources (plants and microorganisms) are considered.

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... Tamiflu (oseltamivir phosphate), the most clinically effective anti-influenza drug, is currently manufactured from shikimic acid, its key precursor [1,2]. Plant products from the Illiciaceae family provide most shikimic acid, but substantial production is found only in few species [3][4][5][6]. More than 40 species of Illiciaceae are found around the world, many of which are toxic. ...
... Chinese star anise (Illicium verum Hook. f., Bajiao) represents a cultivated species with a high content of shikimic acid; it is famous for its use as both spice and medicine [3,[6][7][8]. The fruits of the genus Illicium Mangcao (I. ...
... and I. lanceolatum A. C. Smith) are morphologically similar and easily confounded [7,8]. According to its growing demand, the current shikimic acid manufacturing processes, including the tricky extraction of shikimic acid from microorganisms, have made significant advances already but not matured enough to provide for oseltamivir's production [5,6]. In case of an influenza outbreak, the price increase of Chinese star anise may give unethical suppliers an incentive to adulterate with cheaper counterfeits and increase prices, whereas lowering quality; in this scenario, poisonings are inevitable. ...
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Background: Anisatin is a neurotoxic sesquiterpene dilactone wildly found in plants of the family Illiciaceae. Due to morphological similarities among Illiciaceae fruits, fatal poisonings are frequent. Objective: This study is aimed at developing a rapid, simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine anisatin's bioavailability in mouse blood and the method's application to pharmacokinetics. Methods: Blood samples were preprocessed by protein precipitation using acetonitrile. Salicin (internal standard, IS) and anisatin were gradient-eluted by a mobile phase of methanol and water (0.1% formic acid) in a UPLC BEH C18 column. This step involved using an electrospray ionization source of anisatin at a mass-to-charge ratio (m/z) of 327.1 → 127.0 and IS at m/z 285.1 → 122.9 in the negative ion mode with multiple reaction monitoring. Results: The calibration curve ranged from 1 to 2000 ng/ml (r > 0.995), with the method's accuracy ranging from 86.3% to 106.9%. Intraday and interday precision were lower than 14%, and the matrix effect was between 93.9% and 103.3%. The recovery rate was higher than 67.2%. Conclusions: The developed UPLC-MS/MS method was successfully used for a pharmacokinetic study of oral (1 mg/kg) and intravenous (0.5 mg/kg) administration of anisatin to mice-the absolute bioavailability of anisatin in the mouse blood was 22.6%.
... Despite recent advances in the processes of chemical and microbial synthesis as viable alternatives (Ghosh et al., 2012;Kim and Park, 2012;Rawat et al., 2013;Borah, 2015;Kongkathip et al., 2015;Martínez et al., 2015;Frost and Frost, 2016;Bilal et al., 2018;Candeias et al., 2018), non-toxic shikimic acid from plants remains the raw material of choice for the large-scale production of this antiviral. Shikimic acid can be found in the tissues of many plant species, in quantities varying from 0.001% to 24.5% by dry mass (Bochkov et al., 2012), including the dry fruits of different Illicium species (Avula et al., 2009). Plant species containing shikimic acid are distributed in different regions of the world (Raghavendra et al., 2009;Frost and Frost, 2016). ...
... Similar results were found in the seeds, seed coats, roots, and stems of C. brasiliense (not shown). Moreover, the analytical methods (HPLC, direct-infusion-MS and NMR) applied herein are satisfactory compared with the extraction and quantification procedures of shikimic acid from plants of the genus Illicium and other plant species (Avula et al., 2009;Bochkov et al., 2012). ...
... Currently, Chinese star anise is the main source of commercial production of shikimic acid, but other plant species contain this compound, which accumulates differently in their tissues (Enrich et al., 2008;Avula et al., 2009;Bochkov et al., 2012;ETC group, 2012). Comparative results between plant species indicate that Illicium religiosum (fruits), Illicium lanceolatum (fruits), Alangium salvifollium (roots), Actaea pachypoda (whole plant), Symphytum officinalis (leaves), Ribes aureum (whole plant), Pistacia lentiscus (whole plant), and Terminalia arjuna (fruits) contain 11.8-24.5% of shikimic acid on a dry mass basis (Avula et al., 2009;Bochkov et al., 2012). ...
Article
Shikimic acid is the starting material for the synthesis of the antiviral oseltamivir phosphate, a front-line combatant against the human influenza A and B viruses. Nowadays, the demand for shikimic acid is met by seeds of Chinese star anise (Illicium verum), which grows exclusively in southern China. In the current work, the Calophyllum brasiliense plant is suggested as an alternative source of natural shikimic acid, which was extracted, purified and quantified by high performance liquid chromatography. The presence of shikimic acid in the extract of C. brasiliense was confirmed by nuclear magnetic resonance and mass spectrometry analysis. By using a simple and rapid extraction procedure, we showed that the content of shikimic acid in C. brasiliense leaves is 3.79%. Because C. brasiliense has some additional advantages over Chinese star anise, such as geographical distribution, ecological plasticity, natural regeneration, and versatility regarding large-scale cultivation, it may be a viable and promising source of shikimic acid, with potential industrial uses.
... Shikimic acid (SA, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, C 7 H 10 O 5 ) was originally known as an extract obtained from Illicium anisatum (Japanese star anise) and Illicium verum (Chinese star anise), but can be obtained from dozens of plants 7,8 . SA is known to have antimicrobial, antioxidant, anti-inflammatory, and analgesic effects, and was used as an essential starting material for industrial synthesis of the antiviral oseltamivir (Tamiflu ® ) 7,8 . ...
... Shikimic acid (SA, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, C 7 H 10 O 5 ) was originally known as an extract obtained from Illicium anisatum (Japanese star anise) and Illicium verum (Chinese star anise), but can be obtained from dozens of plants 7,8 . SA is known to have antimicrobial, antioxidant, anti-inflammatory, and analgesic effects, and was used as an essential starting material for industrial synthesis of the antiviral oseltamivir (Tamiflu ® ) 7,8 . Recently, it has been reported that SA is a major component of plant stem cells or callus that induces tissue regeneration when a plant is injured 9 . ...
... www.nature.com/scientificreports/ SA is a key hydroaromatic intermediate in the essential aromatic amino acid biosynthesis and is known to be extracted from various plants 7,8 . There have been many studies on the various pharmacological effects of SA; however, there was no study on the effect of topical application of SA on human HFs. ...
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Shikimic acid (SA) has recently been found to be a major component of plant stem cells. The exact effects of SA on human hair follicles (HFs) is unknown. The purpose of this study was to examine the effects of SA on hair growth. We investigated the effect of SA on an in vivo C57BL/6 mouse model. We examined the expression of mannose receptor (MR), which is a known receptor of SA, in human HFs and the effect of SA on human dermal papilla cells (hDPCs), outer root sheath cells (hORSCs), and on ex vivo human hair organ culture. SA significantly prolonged anagen hair growth in the in vivo mouse model. We confirmed expression of the MR in human HFs, and that SA increased the proliferation of hDPCs and hORSCs. It was found that SA enhanced hair shaft elongation in an ex vivo human hair organ culture. SA treatment of hDPCs led to increased c-myc, hepatocyte growth factor, keratinocyte growth factor and vascular endothelial growth factor levels and upregulation of p38 MAPK and cAMP response element-binding protein levels. Our results show that SA promotes hair growth and may serve as a new therapeutic agent in the treatment of alopecia.
... Shikimic acid (SA, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) is a valuable compound, including six-carbon cyclitol with three chiral carbons and a carboxylic-acid functional group; thus, it can be used as an important precursor for the synthesis of many bioactive compounds [1][2][3]. In recent years, SA has gained great interest as a starting material for industrial synthesis of the anti-influenza drug oseltamivir phosphate (Tamiflu ® ). ...
... SA widely exists in a variety of plants, especially in the fruit of Chinese star anise (Illicium verum). However, there are many disadvantages of the plant extraction method, such as limitations of raw materials, low yield, a costly plant-based extraction procedure, and strong destruction to the natural environment [1,3]. Therefore, the traditional plant extraction method cannot meet the increasing demand for SA. ...
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Shikimic acid (SA) is a key intermediate in the aromatic amino-acid biosynthetic pathway, as well as an important precursor for synthesizing many valuable antiviral drugs. The asymmetric reduction of 3-dehydroshikimic acid (DHS) to SA is catalyzed by shikimate dehydrogenase (AroE) using NADPH as the cofactor; however, the intracellular NADPH supply limits the biosynthetic capability of SA. Glucose dehydrogenase (GDH) is an efficient enzyme which is typically used for NAD(P)H regeneration in biocatalytic processes. In this study, a series of NADPH self-sufficient whole-cell biocatalysts were constructed, and the biocatalyst co-expressing Bmgdh–aroE showed the highest conversion rate for the reduction of DHS to SA. Then, the preparation of whole-cell biocatalysts by fed-batch fermentation without supplementing antibiotics was developed on the basis of the growth-coupled L-serine auxotroph. After optimizing the whole-cell biocatalytic conditions, a titer of 81.6 g/L SA was obtained from the supernatant of fermentative broth in 98.4% yield (mol/mol) from DHS with a productivity of 40.8 g/L/h, and cofactor NADP+ or NADPH was not exogenously supplemented during the whole biocatalytic process. The efficient relay-race synthesis of SA from glucose by coupling microbial fermentation with a biocatalytic process was finally achieved. This work provides an effective strategy for the biosynthesis of fine chemicals that are difficult to obtain through de novo biosynthesis from renewable feedstocks, as well as for biocatalytic studies that strictly rely on NAD(P)H regeneration.
... Bacteria, fungi and plants are capable of synthesizing melatonin at their own through shikimic acid pathway utilizing either carbon dioxide or erythrose-4-phosphate or phosphoenolpyruvate as the source (42, 71,72). However, the amino acid tryptophan has been identified as the initial precursor of melatonin synthesis in animals. ...
... Various vegetables, herbs and fruits have been identified as source of melatonin (109,124,125). Moreover, evolution has loaded plants with all the enzymes required to synthesize tryptophan, the precursor of melatonin so that scarcity of tryptophan can't limit the synthesis of the indoleamine in plants (72) such as in animals. Hence, exposure of plants to severe oxidative stress is the driving force in selecting melatonin as an on-site antioxidant to protect them from environmental insults (126, 127). ...
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At the beginning of life, natural selection is and still the principal driving force for the evolution of all organisms to adapt in the particular environments of the earth. As a result, ultimately neither the strongest, nor the supreme intelligent but the most adaptable species win the race. Not only the organisms, but also the elements which are necessary for survival of them also undergo extreme evolution. These include DNA, proteins and other biochemical molecules. However, melatonin, an indoleamine, presents in the early life form remains unchanged in its structure from unicellular organisms to mammals. When it was discovered, it was considered to be a neuronal hormone produced exclusively in the pineal gland of vertebrates. The latter discovery of its presence in primitive bacteria drives the melatonin research in different directions. Its primary function is serving as an antioxidant in all organisms. Its chemical structure is perfect to scavenge free radicals and thus, this molecule is preserved from bacteria to mammals. However, this molecule acquired many additional functions during evolution. These include circadian regulation, immuno-enhancement, oncostatic, anti-inflammatory and anti-aging activities. In the review, we are trying to present hypothetical and most plausible chronological events in the functional evolvements of melatonin during the process of evolution.
... -8 ) (FIGURE 3). Different species yielded SA at various levels ranged from 0.001% to 24.5%, the highest content reported for I. religiosum [18] . In our results, the SA content found of 5.64 % on dry basis in C. Japonica is on the range compared to other species related by Bochkov et al. [18] . ...
... Different species yielded SA at various levels ranged from 0.001% to 24.5%, the highest content reported for I. religiosum [18] . In our results, the SA content found of 5.64 % on dry basis in C. Japonica is on the range compared to other species related by Bochkov et al. [18] . ...
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Oseltamivir phosphate (OSP), marketed under the brand name of Tamiflu®, is a potent inhibitor of viral neuraminidase, a glycoside hydrolase enzyme essential for viral replication. OSP is also important to control influenza virus (H1N1) and is produced mainly from shikimic acid (SA) extracted from plants. The main source of SA is from seeds of I. verum. Alternatives to meet the worldwide demand are necessary. One of this is Cryptomeria japonica. In this study, we found a content of 56.36 mg.kg-1 of SA in dried biomass for C. japonica, while for I.verum, the traditional source, was 96.57 mg.kg-1. Due to the fact of C. japonica is a tree, exploited for commercial production, it can be a renewable and reliable source SA for OSP production.
... Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) was initially extracted from Illicium species, including I. anisatum and I. verum [1,2]. Shikimic acid is a critical starting material for semi-total synthesis of oseltamivir, which is used to treat and prevent influenza caused by the A and B viruses [1]. ...
... Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) was initially extracted from Illicium species, including I. anisatum and I. verum [1,2]. Shikimic acid is a critical starting material for semi-total synthesis of oseltamivir, which is used to treat and prevent influenza caused by the A and B viruses [1]. ...
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Shikimic acid, a critical starting material for the semi-total synthesis of oseltamivir to treat and prevent influenza, exerts many pharmacological effects. However, the optimal bioanalytical method has not been adequately defined. We used liquid chromatography-tandem mass spectrometry to quantitate shikimic acid in rat plasma and studied its pharmacokinetics after intragastric and intravenous administration. Plasma was spiked with an internal standard, and the proteins were precipitated with acetonitrile, followed by solvent evaporation and reconstitution of the mobile phase. Shikimic acid was separated on a hydrophilic reverse-phase column and showed a mass transition ([M-H]−) at m/z 173.4→136.6. Shikimic acid exhibited bi-exponential decay after intravenous dosing, with a rapid distribution (5.57 h−1) up to 1 h followed by slow elimination (0.78 h−1). The steady state distribution and clearance volumes were 5.17 and 1.79 L/h/kg, respectively. After intragastric administration, the shikimic acid level peaked at about 3 h, and the material then disappeared mono-exponentially with a half-life of 1.3 h. A double peak phenomenon was observed. The absolute oral bioavailability was about 10% in rats. We explored the relationship between the pharmacokinetics and pharmacodynamics of shikimic acid.
... www.nature.com/scientificreports/ produced by the synthesis pathway of lignin, amino acids, alkaloids, phenolics, and phenylpropanoids of plants and microorganisms 43,44 , with use as an important material in the pharmaceutical industry. Saponin was also found in peel extract at peak 24 with retention time of 40.1 min and m/z 986.50. ...
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An accelerated solvent extraction method was used to recover polyphenol-rich crude extract from rambutan (Nephelium lappaceum L.) peel, a waste product from the canning industry. The influence of extraction parameters including temperature, extraction time and ethanol concentration on extraction yield, total phenolic content, total anthocyanin content, and ABTS antioxidant activity was investigated. A Box-Behnken design and response surface methodology were used to optimize the extraction process. Optimal conditions were obtained at temperature, extraction time, and ethanol concentration of 60 °C, 34 min, and 54 vol%, respectively. These optimum conditions gave 333.01 ± 5.84 mg gallic acid/g, 318.28 ± 5.56 mg cyanidin-3-O-glucoside/g, and 3.05 ± 0.04 mmol Trolox/mg for total phenolic content, total anthocyanins content, and ABTS activity, respectively with extraction yield of 28.68 ± 1.48 wt%. Important active compounds found in the extract were geraniin, ellagic acid, shikimic acid and corilagin. Crude extract concentrations of 50–500 mg/kg retarded linoleic acid oxidation but efficacy was lower than synthetic antioxidants at 200 mg/kg. The current findings indicated that accelerated aqueous ethanol extraction was an effective method for the recovery of a crude extract rich in polyphenols from rambutan peel with the potential to be used as a natural antioxidant.
... Higher amounts of shikimic acid were reported at harvest in Spanish avocados (0.24 g kg −1 DW) compared to Chilean avocados (0.14 g kg −1 DW) and decreased from harvest to edible ripeness ( Figure 5). Shikimic acid is a natural organic compound, and an important intermediate in the biosynthesis of lignin, aromatic amino acids (phenylalanine, tyrosine, and tryptophan), and most alkaloids of plants [49]. Its content and accumulation depend on different ongoing metabolic processes. ...
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Avocado consumption and trade are increasing worldwide, with North America and Europe being the main importing regions. Spain is the major European avocado producer (90% of the production), yet it only supplies 10% of the market. Consequently, more than 90% of the avocados consumed in Europe are imported from overseas, mainly from Chile and Peru. In this work, the Life Cycle Assessment (LCA) impact associated with the transport of two avocado supply chains (short (Spanish) and long (Chilean)) and the effect of the fruit origin and distance of both chains on primary and secondary metabolites from harvest to edible ripeness were evaluated using a gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to diode array detection (LC-DAD) based metabolite analysis. The LCA transport impact of the fresh supply chain from production centers in Chile (Quillota) and Spain (Malaga), and then the distribution to several cities in Europe, suggested road export from Spain to European capitals to have the lowest impact (0.14 to 0.22 kg CO2 eq/kg of avocado). When export from Chile was considered, the option of oceanic freight to European ports closer to final destinations was clearly a better option (0.21 to 0.26 kg CO2 eq/kg) than via the Algeciras port in Spain followed by road transport to final destinations in European capitals (0.34 to 0.43 kg CO2 eq/kg), although the situation could be somewhat different if the avocados are transported from the destination ports in northern Europe to long-distance capitals in other European countries. Fruit origin had a significant impact on avocado primary and secondary metabolites. The conditions of the supply chain itself (10 d in cold storage in regular conditions vs. 30 d cold storage + controlled atmosphere conditions) largely influence the fate of some metabolites that certainly affect the pool of metabolites at edible ripeness. The long-assumed hypothesis that the longer the supply chain the more negative impact on nutritional and functional compounds might not hold in this case, as long as transport conditions are adequate in terms of temperature, atmosphere conditions, and time considering distance from origin to destination.
... Yet, it has no chemophenetic importance since it is quite ubiquitous in plants having been isolated also in other families like Arecaeae with Phoenix dactylifera L., Pinaceae with Picea glauca (Moench) Voss, Rosaceae with Malus baccata Loisel. and Iridaceae with Iris pseudacorus L. (Bochkov et al., 2012). ...
Article
The phytochemical analysis on the leaves of a new population of Araucaria columnaris (G.Forst.) Hook. was reported. Seven compounds were identified i.e., 15-agathic acid methyl ester (1), ladanein (2), 7,4′,7″,4‴-tetra-O-methyl-robustaflavone (3), 3-O-trans-p-coumaroyl-quinic acid (4), 4-O-trans-p-coumaroyl-quinic acid (5), 5-O-trans-p-coumaroyl-quinic acid (6) and shikimic acid (7). Chromatographic and spectroscopic techniques were utilized for this. Their presence is important from the chemophenetic point of view, but further research is necessary to make final conclusions on this species.
... It is well understood that some enzymes of primary metabolism catalyze the formation of products that can be channeled into the pathways of secondary metabolites [113]. Glucose degradation via the pentose phosphate cycle forms erythrose-4-phosphate, which can react with phosphoenolpyruvate to yield shikimic acid, an intermediate product connecting primary and secondary metabolism [114]. Shikimic acid is a precursor for many aromatic amino acids including tryptophan and tryptophan derivatives. ...
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The inside of a space-faring vehicle provides a set of conditions unlike anything experienced by bacteria on Earth. The low-shear, diffusion-limited microenvironment with accompanying high levels of ionizing radiation create high stress in bacterial cells, and results in many physiological adaptations. This review gives an overview of the effect spaceflight in general, and real or simulated microgravity in particular, has on primary and secondary metabolism. Some broad trends in primary metabolic responses can be identified. These include increases in carbohydrate metabolism, changes in carbon substrate utilization range, and changes in amino acid metabolism that reflect increased oxidative stress. However, another important trend is that there is no universal bacterial response to microgravity, as different bacteria often have contradictory responses to the same stress. This is exemplified in many of the observed secondary metabolite responses where secondary metabolites may have increased, decreased, or unchanged production in microgravity. Different secondary metabolites in the same organism can even show drastically different production responses. Microgravity can also impact the production profile and localization of secondary metabolites. The inconsistency of bacterial responses to real or simulated microgravity underscores the importance of further research in this area to better understand how microbes can impact the people and systems aboard spacecraft.
... Natural compounds such as plant-derived compounds used in traditional Chinese herbal medicines have long been considered as seeds for new drugs (29)(30)(31)(32)(33)(34). In particular, the biocompatibility of herbal medicine-derived compounds is expected to be high because they have already been registered as drugs for multiple applications in humans. ...
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Adjuvants are important vaccine components, composed of a variety of chemical and biological materials that enhance the vaccine antigen-specific immune responses by stimulating the innate immune cells in both direct and indirect manners to produce a variety cytokines, chemokines, and growth factors. It has been developed by empirical methods for decades and considered difficult to choose a single screening method for an ideal vaccine adjuvant, due to their diverse biochemical characteristics, complex mechanisms of, and species specificity for their adjuvanticity. We therefore established a robust adjuvant screening strategy by combining multiparametric analysis of adjuvanticity in vivo and immunological profiles in vitro (such as cytokines, chemokines, and growth factor secretion) of various library compounds derived from hot-water extracts of herbal medicines, together with their diverse distribution of nano-sized physical particle properties with a machine learning algorithm. By combining multiparametric analysis with a machine learning algorithm such as rCCA, sparse-PLS, and DIABLO, we identified that human G-CSF and mouse RANTES, produced upon adjuvant stimulation in vitro, are the most robust biological parameters that can predict the adjuvanticity of various library compounds. Notably, we revealed a certain nano-sized particle population that functioned as an independent negative parameter to adjuvanticity. Finally, we proved that the two-step strategy pairing the negative and positive parameters significantly improved the efficacy of screening and a screening strategy applying principal component analysis using the identified parameters. These novel parameters we identified for adjuvant screening by machine learning with multiple biological and physical parameters may provide new insights into the future development of effective and safe adjuvants for human use.
... From the aerial parts, shikimic acid (114), an antiviral agent, was isolated with a yield of 0.03-3.25% w/w from 1.0 g of plant material (Bochkov et al., 2012;Cardoso et al., 2014;Lenora et al., 2016). Isoascorbic acid (115), ascorbic acid (116), and dehydroascorbic acid (117) were present in the shoot extracts, however, the latter was detected only in the rhizome (Lata and Dubey. ...
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Eichhornia crassipes (Mart.) Solms, commonly known as water hyacinth, is one of the world's most invasive aquatic plants of the Pontederiaceae family occurring in tropical and subtropical regions of the world. Although, E. crassipes causes significant ecological and socioeconomic issues such as a high loss in water resources, it has multipurpose applications since it is famous for many industrial applications such as bioenergy, biofertilizer production, wastewater treatment (absorption of heavy metals), and animal feed. Furthermore, E. crassipes is rich in diverse bioactive secondary metabolites including sterols, alkaloids, phenolics, flavonoids, tannins, and saponins. These secondary metabolites are well known for a wide array of therapeutic properties. The findings of this review suggest that extracts and some isolated compounds from E. crassipes possess some pharmacological activities including anticancer, antioxidant, anti-inflammatory, antimicrobial, skin whitening, neuroprotective, and hepatoprotective activities, among other biological activities such as allelopathic, larvicidal, and insecticidal activities. The present review comprehensively summarizes the chemical composition of E. crassipes, reported to date, along with its traditional uses and pharmacological and biological activities.
... These bioactive compounds in fruits methanolic extract possess effective antifungal [37] and antimicrobial activity [38], including polysaccharides, which act as an osmoprotective mechanism of plants involved in immunity [39]; organic acids used as herbicides, utilized as a precursor for the synthesis of the antiviral drugs and antibacterial agents [40,41]; fatty acids which play an important role in fungal resistance [42,43]; and antioxidant components, which help the plant to protect itself against various types of oxidative damage [44]. ...
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Zizyphus spina-christi L. has antimicrobial properties because of the presence of biologically active compounds. Alternaria is an opportunistic pathogen that causes leaf spots, rots, and blights on a variety of plant parts. This study aimed to reduce the usage of synthetically derived fungicides. Identification of the bioactive components present in leaves and fruits methanolic extracts of Z. spina-christi was performed using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). The efficacy of the two methanol extracts was tested against (a) in vitro fungal growth and (b) pathogenicity control on non-wounded and wounded tomato fruits. The results revealed that gallic acid and ellagic acid were the major components in leaves extract while quercetin was the major component in fruits extract. In addition, Phenol, 2,5-bis(1,1-dimethylethyl) (40.24%) and Decane, 2-methyl-(18.53%) were the most abundant components in the leaf extract, and the presence of D-mannonic acid, 2,3,5,6-tetrakis-o-(trimethylsilyl), and γ-lactone (22.72%) were major components in fruits extract. The methanolic extracts of Z. spina-christi leaves and fruits demonstrated significant antifungal activity against the growth of Alternaria alternata, A. citri, and A. radicina with variable inhibition percentages at different concentrations. Pathogenicity was increased when the skin was injured, as expected. Both extracts reduced the percentage of infected fruits.
... Shikimic acid acts through the mannose receptor and the MYD88/P38/CREB signaling pathway Shikimic acid is an important intermediate in the biosynthesis of lignin and most alkaloids of plants. It has been found in many organs, such as stems, leaves, and fruits, in a variety of plants [24]. Industrially, it is generally utilized as a starting material for the synthesis of oseltamivir, a drug against the influenza virus [25]. ...
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Background The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. Methods Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO 2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. Results The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. Conclusions These results indicate that shikimic acid is an effective agent for tissue regeneration.
... In view of the huge demand of shikimic acid, the key raw material of antiviral drug Tamiflu [18,19], seeking a suitable and effective separation method for shikimic acid with social and economic worth, is of great concern and urgency. Conventional methods applied in the separation of shikimic acid, such as ion exchange [20], electrostatic adsorption [21] and chromatography [22], have some limits unavoidable. The common defects are complexity of the operation, small adsorption capacity, poor selectivity and timeconsuming. ...
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Polymer of cyclodextrin (CD) is still of great sustainable interest in the scientific research attributing to its excellent physicochemical properties. Owing to its water solubility and superior binding capacity, CD is usually modified through various strategies to exploit its application area. Herein, for the first time, magnetic β-cyclodextrin (β-CD) polymer is endowed with boronate affinity property via mild chemical modifications to specifically separate natural drug raw material shikimic acid (SA). The uniform morphology, magnetic response ability and composition analysis of the porous adsorbent were highly supported by the characterizations. The capture process towards SA depending on the pH value is explored in detail by adsorption kinetics, equilibrium, selectivity and reusability. It is found that specific recognition sites decorated on the surface of magnetic β-CD provides strength support for selective adsorption and separation of shikimic acid. The prepared adsorbent shows high adsorption quantity (Q, mg g−1) of 31.60 mg g−1 at 25 °C, high specific recognition and good adsorption capacity (above 83.7%) and stability after five cycles. This study gives a new sight on the utilization of porous β-CD-based material by grafting functional boric acid group for specific capture of natural cis-diol-containing compounds.
... [17] SA is also a promising precursor compound for the industrial synthesis of the antiviral Oseltamivir (this drug against the H5N1 influenza virus is administered to treat and prevent all the known strains of influenza virus). [18] However, with the growth of the GBL processing industry, more wash effluent is being generated, causing economic and environmental problems. If this natural source is exploited to produce SA, it may not only maximise the economic value of Ginkgo biloba but also protect the environment. ...
Article
Objectives The present study investigated the feasibility of preparing high-purity shikimic acid (SA) from the chromatography wash effluent of Ginkgo biloba leaf extract by macroporous resin. Methods First, static/dynamic adsorption and desorption were conducted to screen out the optimal resin. Second, the key parameters of the chromatographic process were optimised with face-centred central composite design (CCD). Third, wash effluent indices were measured, different batches of wash effluent were used to prepare SA under the optimised parameters, and the effect of varying feed solution compositions on final products was investigated. Key findings It was found that the final purity and recovery rate of SA prepared with ADS-21 resin were not lower than 70 and 60%, respectively, when the purity of SA in the wash effluent was higher than 21.4%. The quality of the final product can be predicted based on the properties of wash effluent. Conclusions The proposed method could not only provide a simple, green and promising approach for the large-scale purification of SA from wash effluent but also be used to develop process intermediate quality standards for other natural products.
... Figure 4 indicates the suggested pathway for the production of melatonin. Tryptophan availability in the plants and microorganisms to initiate the pathway is assured by Shikimic acid pathways, which is followed in most of the plants and microorganisms except animals where tryptophan and other aromatic amino acids are supplied by food source The synthesis of the tryptophan in the plants, microalgae, and other prokaryotes also exhibit a complex process comes under Shikimic acid pathways where tryptophan can be integrated in the beginning with D-erythrose-4-phosphate and phosphoenolpyruvate, in phototrophs eventually with carbon dioxide (Bochkov et al., 2012). ...
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Melatonin was discovered as a pineal gland hormone in animals and is now more significantly known as a signaling molecule in plants' biotic and abiotic stressors. Melatonin has been traced back to prokaryotic organisms during evolution and its primary function of antioxidant scavenging free radicals in photosynthetic prokaryotic bacteria is a lesser explored and exciting area for further research globally. The authors at IIT Delhi are trying to establish its potential role in stress management in agriculture. The present manuscript addresses the biosynthetic pathways hitherto suggested by scientists. In this manuscript, the potential scope of melatonin in agriculture as a growth promoter, post-harvest loss inhibitor, and signaling and quality improvement molecule is envisaged.
... Additionally, calceolarioside B (5), phenylethanoid glycoside, has been exhibited to inhibit TNF-α-induced IL-6 production in MG-63 cells [35]. Furthermore, rutin (7) has been suggested as a candidate therapeutic agent for treatment of inflammatory diseases through inhibition of the high mobility group box 1-stimulated production of IL-6 [36], isoacteoside (12) significantly inhibited the production of phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-induced pro-inflammatory mediators in HMC-1 cells [16]. Therefore, the aforementioned compounds are likely responsible for the anti-inflammatory property of AL, suggesting that the anti-inflammatory activity of AL should be modulated by the suppression of pro-inflammatory mediators and cytokine production. ...
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Plant extracts have gained more attention as natural therapeutic agents against inflammation characterized by an overproduction of several inflammatory mediators such as reactive oxygen species and pro-inflammatory cytokines. Although Abeliophyllum distichum Nakai is generally known for its ornamental value, recent pharmacological research has demonstrated its potential therapeutic properties. Thus, to further evaluate the applicability of A. distichum in the food, cosmetic, and medical industries, we identified the phytochemicals in three organ extracts (fruits: AF, branches: AB, leaves: AL) of A. distichum and determined their antioxidant and anti-inflammatory activities. Using UPLC-ESI-Q-TOF-MS, a total of 19 compounds, including dendromoniliside D, forsythoside B, isoacteoside, isomucronulatol 7-O-Glucoside, plantamajoside, and wighteone were identified in the A. distichum organ extracts. AB exhibited a strong reducing power, an oxygen radical antioxidant capacity, and radical scavenging values compared with other samples, whereas AL exhibited the best anti-inflammatory properties. Gene expression, western blot, and molecular docking analyses suggested that the anti-inflammatory effect of AL was mediated by its ability to suppress lipopolysaccharide (LPS)-induced production of reactive oxygen species and/or inhibit LPS-stimulated activation of extracellular signal-regulated protein kinases (ERK1/2) in RAW264.7 cells. Collectively, these results indicate that AL is a potential source of phytochemicals that could be used to treat inflammation-associated diseases.
... In this study, we focused on analyzing the concentration of shikimic acid from A. absinthium extract; thus, the HPLC results were analyzed to compare the extract with shikimic acid (standard compound) according to retention time. The data showed that the amount of shikimic acid in A. absinthium was not as high as that reported in an earlier study in other plants [59]. However, another study claimed that shikimic acid was one of the most abundant bioactive compounds among the seven bioactive compounds in A. absinthium [60]. ...
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Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL A. absinthium extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the A. absinthium extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of A. absinthium extract and its mechanism of action against cisplatin-induced renal injury.
... Glyphosate is a systemic herbicide, used as a positive control in phytotoxicity and cytotoxicity assays as it acts directly on the roots in a negative and prolonged manner, also presenting genotoxicity (Andrade et al., 2010;Rodrigues et al., 2013;Loren et al., 2019). When in contact with plant tissue, glyphosate enters the extracellular matrix and, upon reaching the cytoplasm, it is transported via phloem and distributed to the cellular tissues, causing lethal effects to the plant and also inhibiting the shikimate pathway in plants, consequently interfering with the biosynthesis of lignins and aromatic amino acids, such as tryptophan (Bochkov et al., 2012). Toxicity tests of glyphosate formulations in Lenna minor evidence their inhibitory power on the synthesis of chlorophyll a and b, carotenoids, photosystem II activity, besides increasing the shikimic acid content by 15 to 21% with the application of glyphosate in low concentrations (Sikorski et al., 2019). ...
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... Shikimic acid is also an important starting material for the synthesis of anticancer drugs such as (+)-zeylenone (Liu et al., 2004). Current industrial production of shikimic acid primarily involves its extraction from the seeds of the Chinese star anise plant (almost 80% or more), Illicium verum, and subsequent chemical synthesis (Bochkov et al., 2012;Ghosh et al., 2012;Rawat et al., 2013). However, these processes are complex and incur problems such as limitations of raw material and high costs. ...
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The production of aromatic compounds by microbial production is a promising and sustainable approach for producing biomolecules for various applications. We describe the metabolic engineering of Corynebacterium glutamicum to increase its production of shikimic acid. Shikimic acid and its precursor-consuming pathways were blocked by the deletion of the shikimate kinase, 3-dehydroshikimate dehydratase, shikimate dehydratase, and dihydroxyacetone phosphate phosphatase genes. Plasmid-based expression of shikimate pathway genes revealed that 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase, encoded by aroG, and DHQ synthase, encoded by aroB, are key enzymes for shikimic acid production in C. glutamicum. We constructed a C. glutamicum strain with aroG, aroB and aroE3 integrated. This strain produced 13.1 g/L of shikimic acid from 50 g/L of glucose, a yield of 0.26 g-shikimic acid/g-glucose, and retained both its phosphotransferase system and its pyruvate kinase activity. We also endowed β-glucosidase secreting ability to this strain. When cellobiose was used as a carbon source, the strain produced shikimic acid at 13.8 g/L with the yield of 0.25 g-shikimic acid/g-glucose (1 g of cellobiose corresponds to 1.1 g of glucose). These results demonstrate the feasibility of producing shikimic acid and its derivatives using an engineered C. glutamicum strain from cellobiose as well as glucose.
... Shikimic acid ranged from 0.198 to 0.520 mg kg −1 (RSD 3.1−4.6%); it is an important intermediate in the biosynthesis of lignin, aromatic amino acids and most alkaloids in plants and microorganisms [47]. This study is the first on the quantification of flavonoids including flavonols, flavan-3-ols, flavanone and anthocyanins, alkaloid (quinine), xanthone, iridoid and secoiridoids. ...
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For the first time the volatile fraction of coffee silverskin has been studied focusing on odor-active compounds detected by gas chromatography-olfactometry/flame ionization detector (GC-O/FID) system. Two approaches, namely headspace (HS) analysis by solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) and odor-active compounds analysis by gas chromatography-olfactometry/flame ionization detector (GC-O/FID), have been employed to fully characterize the aroma profile of this by-product. This work also provided an entire characterization of the bioactive compounds present in coffee silverskin, including alkaloids, chlorogenic acids, phenolic acids, flavonoids, and secoiridoids, by using different extraction procedures and high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) system. Coffee silverskin was shown to be a good source of caffeine and chlorogenic acids but also of phenolic acids and flavonoids. In addition, the fatty acid composition of the coffee silverskin was established by GC-FID system. The results from this research could contribute to the development of innovative applications and reuses of coffee silverskin, an interesting resource with a high potential to be tapped by the food and nutraceutical sector, and possibly also in the cosmetics and perfumery.
... Shikimic acid accumulates in inert metabolically tissues. Also, the shikimic acid decreases under stress as it is used in the synthesis of phenolic compounds which help in the resistance against the stress (Bochkov et al. 2012;Naguib 2018;Naguib and Abdalla 2019). The shikimic acid content decreased in the two calli groups under PEG treatment but in the case of nonprimed samples, the shikimic acid content was significantly higher than that in the primed one (Fig. 4). ...
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The induction of secondary metabolites under osmotic stress is well documented. However, cell death is probably due to osmotic stress. This work tries to study the synergetic effect of hydropriming and polyethylene glycol (PEG) on enhancing the secondary metabolites production in fenugreek callus cultures without facing cell death. PEG initiates the stress and the hydropriming increase the plant cell response against the stress. Fenugreek calli were initiated from hypocotyl of two groups of seeds, the first was hydroprimed overnight before germination, the second remained dry. Three months old calli of the two groups were subcultured on media containing two different concentration of PEG (5, 10%). The calli growth, biochemical analysis, secondary metabolism keys, and secondary metabolites were determined after 4 weeks. PE induced oxidative stress, which increased the membrane lipid peroxidation and decreased cell viability and growth. Hydropriming enhanced the activity of antioxidant enzymes, regulating the reactive oxygen species level, accumulating the osmolytes and secondary products. Therefore the primed callus can tolerate the osmotic stress initiated with PEG. Consequently, cell biomass increased and not affected by PEG treatment. On the other hand, the calli from non-primed seeds have a significant decrease in fresh weight, and dry weight under the higher PEG treatment. The hydropriming protected the growth of the cells under PEG treatment with a high content of secondary metabolites and high antioxidant machinery. The synergetic effect of hydropriming and PEG can be used as a simple and low-cost way to produce valuable compounds in commercial industrial bioreactors.
... Shikimic acid is utilized for industrial synthesis of the oseltamivir (antiviral), zeylenone (employed as a preparation for chemotherapy of cancer), and monopalmityloxy shikimic acid (anticoagulant activity). In addition, shikimic acid derivatives represent a great interest for agriculture because many of them are used as herbicides and antibacterial agents [46]. ...
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The metabolite profiling associated with the antioxidant potential of Amazonian fruits represents an important step to the bioactive compound′s characterization due to the large biodiversity in this region. The comprehensive bioactive compounds profile and antioxidant capacities of mamey apple (Mammea americana), camapu (Physalis angulata), and uxi (Endopleura uchi) was determined for the first time. Bioactive compounds were characterized by ultra-performance liquid chromatography coupled to high resolution mass spectrometry (UPLC-MSE) in aqueous and ethanolic extracts. Globally, a total of 293 metabolites were tentatively identified in mamey apple, campau, and uxi extracts. The main classes of compounds in the three species were terpenoids (61), phenolic acids (58), and flavonoids (53). Ethanolic extracts of fruits showed higher antioxidant activity and total ion abundance of bioactive compounds than aqueous. Uxi had the highest values of phenolic content (701.84 mg GAE/100 g), ABTS (1602.7 μmol Trolox g−1), and ORAC (15.04 μmol Trolox g−1). Mamey apple had the highest results for DPPH (1168.42 μmol TE g−1) and FRAP (1381.13 μmol FSE g−1). Nuclear magnetic resonance (NMR) spectroscopy results showed that sugars and lipids were the substances with the highest amounts in mamey apple and camapu. Data referring to chemical characteristics and antioxidant capacity of these fruits can contribute to their economic exploitation.
... It has been reported in the literature that shikimic, citric, aconitic, malic and fumaric acids show positive activity against gram negative bacteria (Sousa et al., 2008). On the other hand, shikimic acid is generally used as the starting material for the industrial synthesis of the antiviral drug Oseltamivir (this drug is effective against the H5N1 influenza virus and is administered to treat and prevent all known strains of the influenza virus) (Bradley, 2005;Bochkov et al., 2012). In addition, a Chinese research team has synthesized a shikimic acid derivative, triacetylshikimic acid, which exhibits anticoagulant and antithrombotic activities (Huang et al., 2002). ...
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In addition to basic nutrition, plant-based foods provide substantial amounts of bioactive compounds which deliver desirable health benefits. During the last decade, secondary metabolites, also known as phytochemicals, obtained from plants, have aroused special attention by researchers. Amongst such plants, the turnip contains a few valuable components which not only endorse health benefits but also provide healing properties. Various bioactive components, for example peroxidase, kaempferol, phenolic compounds, sulforaphane, organic acids, vitamin K, glucosinolates etc are highlighted in this manuscript. Likewise, numerous minerals, such as copper, manganese and calcium, and organic acids, such as sinapic and ferulic acids and their derivatives, found in different amounts in fresh greens and turnip roots, are also discussed briefly. The current paper is focused on the phenolic compounds, which act as beneficial compounds for human health and can be isolated from plant foods, especially turnip. Due to the presence of bioactive constituents, turnip imparts a positive role with respect to the hepatic injury caused by diabetes, high antioxidant activity and a good hepatoprotective role. The impact of environmental conditions and processing mechanisms on the phenolic compound composition of Brassica vegetables, with special reference to turnip, was also briefly discussed.
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Shikimic acid (SA), a hydroaromatic natural product, is used as a chiral precursor for organic synthesis of oseltamivir (Tamiflu®, an antiviral drug). The process of microbial production of SA has recently undergone vigorous development. Particularly, the sustainable construction of recombinant Corynebacterium glutamicum (141.2 g/L) and Escherichia coli (87 g/L) laid a solid foundation for the microbial fermentation production of SA. However, its industrial application is restricted by limitations such as the lack of fermentation tests for industrial-scale and the requirement of growth-limiting factors, antibiotics, and inducers. Therefore, the development of SA biosensors and dynamic molecular switches, as well as genetic modification strategies and optimization of the fermentation process based on omics technology could improve the performance of SA-producing strains. In this review, recent advances in the development of SA-producing strains, including genetic modification strategies, metabolic pathway construction, and biosensor-assisted evolution, are discussed and critically reviewed. Finally, future challenges and perspectives for further reinforcing the development of robust SA-producing strains are predicted, providing theoretical guidance for the industrial production of SA.
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In recent years, membrane separation technology has become more and more practical in the field of separation and purification due to its simple operation, low energy consumption, high efficiency and no phase change. In this work, shikimic acid molecularly imprinted polymers (SA-MIPs) were uniformly sprayed on the cellulose acetate membrane (CAM) substrate by electrostatic spray deposition (ESD) method for the first time to prepare the boronate affinity membrane (MIPs-PVA/CAM), which could specifically separate shikimic acid (SA). Thanks to the ESD process, the active binding sites were exposed on the surface, avoiding the encapsulation of MIPs in the membrane compared with traditional blending method, meanwhile, averting the contact with excessive polar solvents used in imprinted process to ensure the membrane integrity. In the adsorption test, the maximum adsorption of SA reached 51.57 mg g⁻¹ in 70 min under pH 7.5, indicating the acceptable binding capacity and fast binding rate. Additionally, MIPs-PVA/CAM possesses remarkable binding selectivity towards SA due to boronate affinity and favorable reusability of 7.68% loss after five continuous cycles. According to the results, ESD holds great promise to prepare molecularly imprinted membrane platform with inherent tailored sites for separation of cis-diols compounds.
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Plants of family Clusiaceae are growing in semi-evergreen to evergreen, moist, tropical and lower montane forest mainly native to tropical regions, except Hypericum and Triadenum. Clusiaceae are known for producing a wide range of phytochemicals like isoprenylated xanthones, biflavonoids and anthraquinones. In the present work, water and methanol extracts of the stem and leaves of various species were studied for their total phenolics, flavonoids and antioxidant properties. Phytochemical studies of different species extracts were observed that, species studied having very abundant in phenolics, flavonoids and antioxidants. This study revealed that methanol allowing higher recovery of phytochemicals than water extracts, whereas leaves of all species contained higher amount of total phenolic content (TPC), total flavonoid content (TFC) and antioxidant compounds than stem. In water and methanol extracts, the highest TPC was observed in stem of Calophyllum apetalum (17.48 mg/g) while the lowest TPC in leaves of Garcinia gummigutta (7.08 mg/g) on other hand, TFC was highest in Mammea suriga stem (8.46 mg/g) with lowest content in Calophyllum inophyllum stem (3.12 mg/g). The present investigation is the first comprehensive report on Clusiaceae species with respect to phytochemicals and antioxidants study from stem and leaves by using water and methanol as solvents. Our findings from this investigation are of considerable interest from pharmaceutical point of view and to provide suitable, sustainable and alternative source of phytochemicals and antioxidants.
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Monitoring of seagrasses has mainly relied on traditional seagrass metrics (e.g., biomass), which deliver reliable information about mortality but are unable to inform about impacts on seagrass health at the very early stages of stress exposure. Metabolomics is a novel molecular technique which can be used for early stress-detection in plants and also for unravelling the underlying mechanisms of stress response. In the Swan-Canning Estuary, south-west Australia, the seagrass Halophila ovalis is impacted by seasonal changes in sediment-and nutrient-stress. To date, it is unknown how H. ovalis responds to these seasonal stressors on a molecular level. Here, we used a combined approach of traditional seagrass metrics and metabolomics to create a holistic picture of seasonal influences on seagrass condition. Leaf samples of H. ovalis were collected from six different locations in the Swan-Canning Estuary in both summer and spring. We detected strong differences in metabolite profiles and relative metabolite abundance between seasons, with growth- and/or development-related metabolites being up-regulated in spring and stress-related (secondary) metabolites being up-regulated in summer. Metabolites were mostly related to leaf δ¹³C signatures, a metric that has been previously associated with variation in light and pH in the Swan-Canning. We demonstrate that a holistic approach which includes metabolomics into ecological monitoring can help to improve our understanding of the mechanisms underlying molecular (stress) responses in seagrasses which is crucial knowledge for management and conservation measures locally and globally.
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Eucalypts are the most planted hardwood trees worldwide because of their very rapid growth, exceptional wood quality and adaptability. However, most commercial species and derived hybrids are sensitive to frost, which remains as the largest obstacle to their introduction in warm/temperate climates. As evergreen species, Eucalypts have developed the ability to tolerate frost events based on physiological and molecular responses triggered by previous exposure to cold temperatures, globally named cold acclimation. To characterize the acclimation process in two species with different tolerance to frost, E. grandis (Eg) and E. benthamii (Eb), seedlings were exposed for different times to low temperatures. Frost tolerance was estimated in leaves by an electrolyte leakage assay, and metabolome and morpho-physiological changes studied and correlated to the observed acclimation responses. Eb showed higher basal frost tolerance and an earlier and stronger acclimation response to cold temperatures than in the frost sensitive Eg. Eb was able to modify several morpho-physiological parameters, with a restriction in plant height, leaf area and leaf fresh weight during acclimation. Metabolome characterization allowed us to differentiate species and strengthen our understanding of their acclimation response dynamics. Interestingly, Eb displayed an early phase of sugar accumulation followed by a rise of different metabolites with possible roles as osmolytes and antioxidants, that correlated to frost tolerance and may explain Eb higher capacity to acclimate. This novel approach has helped us to point to the main metabolic processes underlying the cold tolerance acquisition process in two relevant Eucalyptus species.
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Electrospun micro-/nanofibers with tailor-made specific binding sites are extremely popular due to their tremendous potential in separation applications. In this work, teamed boronate affinity (TBA)-functionalized molecularly imprinted hollow carbon electrospun nanofibers (MI-HCESNFs) derived from ZIF-8/PAN fibers with selective binding sites toward shikimic acid (SA) are presented. Each ingredient used in this strategy plays its own part: HCESNFs with excellent structural characteristics as the highly porous electrospun substrate, KH560 as the grafting material for the follow-up polyethyleneimine (PEI) modification, PEI as the dendritic platform to approach more boronic acid owing to its long chain with abundant amino groups, and TBA molecular group as the functional monomer to specifically bind with SA under the neutral condition. Benefiting from the porous structure, the high density of boronic acid, and the highly accessible imprinted sites on the surface, MI-HCESNFs show strong affinity and selectivity to the SA molecules. The adsorption capacity of MI-HCESNFs can reach 127.8 mg g-1, which is 3.1 times larger than that of the non-imprinted material. Besides, MI-HCESNFs are stable when treated with continuous ultrasonication and can be recycled eight times with a slight loss of 8.615% on the adsorption quantity. This work presents a new strategy to prepare boronate affinity adsorbents based on the electrospinning technique for the capture of SA and also proposes a path for the integration of molecularly imprinted polymers and electrospinning.
Article
Objectives: To investigate the feasibility of using near-infrared spectroscopy for rapid determination of main organic acids in Ginkgo biloba leaf extract (EGBL). Methods: Main organic acids in EGBL were assayed using the HPLC method. Critical factors of the chromatographic separation were optimized by a novel analytical quality by design approach. Partial least squares-discriminant analysis (PLS-DA) was performed to screen the marker components, and principal component analysis (PCA) was utilized to distinguish the different samples. Then, spectral quantification potential was investigated using PLS and support vector machine (SVM) approaches. For modelling, different spectral preprocessing and wavelength selection methods were systematically compared. Key findings: It was found that quinic acid, protocatechuic acid and 6-hydroxykynurenic acid were identified as possible index components. PLS-DA based on contents and PCA based on near-infrared spectra can both effectively distinguish the different EGBL samples. The calibration models with wonderful prediction performance can be both developed by the PLS and SVM algorithms. Conclusions: NIR spectroscopy combined with chemometrics can realize the rapid and non-destructive qualitative and quantitative analysis of EGBL. The proposed method may be applied to quality control of EGBL and other natural products in commercial use.
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Shikimate is a key high-demand metabolite for synthesizing valuable antiviral drugs, such as the anti-influenza drug, oseltamivir (Tamiflu®). Microbial-based strategies for shikimate production have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. In this study, a microbial cell factory using Corynebacterium glutamicum was designed to overproduce shikimate in a fed-batch culture system. First, the shikimate kinase gene (aroK) responsible for converting shikimate to the next step was disrupted to facilitate the accumulation of shikimate. Several genes encoding the shikimate bypass route, such as dehydroshikimate dehydratase (QsuB), pyruvate kinase (Pyk1), and quinate/shikimate dehydrogenase (QsuD), were disrupted sequentially. An artificial operon containing several shikimate pathway genes, including aroE, aroB, aroF, and aroG were overexpressed to maximize the glucose uptake and intermediate flux. The rationally designed shikimate-overproducing C. glutamicum strain grown in an optimized medium produced approximately 37.3 g/L of shikimate in 7-L fed-batch fermentation. Overall, rational cell factory design and culture process optimization for the microbial-based production of shikimate will play a key role in complementing traditional plant-derived shikimate production processes.
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Novel stereodivergent total syntheses of all the seven stereoisomers of (‒)‐shikimic acid [(−)‐SA 1 ] have been systematically performed. (+)‐ ent ‐SA ent ‐ 1 was synthesized from (−)‐SA 1 via 9 steps in 31% overall yield; (‒)‐3‐ epi ‐SA 2 was synthesized from (−)‐SA 1 via 5 steps in 66% overall yield; (+)‐3‐ epi ‐ ent ‐SA ent ‐ 2 was synthesized from (−)‐SA 1 via 7 steps in 43% overall yield; (‒)‐4‐ epi ‐SA 3 was synthesized from (−)‐SA 1 via 11 steps in 32% overall yield; (+)‐4‐ epi ‐ ent ‐SA ent ‐ 3 was synthesized from (−)‐SA 1 via 7 steps in 42% overall yield; (‒)‐5‐ epi ‐SA 4 was synthesized from (−)‐SA 1 via 6 steps in 56% overall yield; and (+)‐5‐ epi ‐ ent ‐SA ent ‐ 4 was synthesized from (−)‐SA 1 via 12 steps in 29% overall yield. The stereochemistry of all the above seven stereoisomers of (−)‐SA 1 were further studied by two dimentional (2D) 1 H NMR technique.
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Novel highly stereoselective syntheses of (+)-streptol and (−)-1-epi-streptol starting from naturally abundant (−)-shikimic acid were described in this article. (−)-Shikimic acid was first converted to the common key intermediate by 11 steps in 40% yield. It was then converted to (+)-streptol by three steps in 72% yield, and it was also converted to (−)-1-epi-streptol by one step in 90% yield. In summary, (+)-streptol and (−)-1-epi-streptol were synthesized from (−)-shikimic acid by 14 and 12 steps in 29 and 36% overall yields, respectively.
Article
The oil palm (Elaeis guineensis) fruit is a source of vegetable oil and various phytonutrients. Phytochemical compounds present in palm oil include tocotrienols, carotenoids, phytosterols, squalene, coenzyme Q10, and phospholipids. Being a fruit, the oil palm is also a rich source of water-soluble phytonutrients, including phenolic compounds. Extraction of phytonutrients from the oil palm vegetation liquor of palm oil milling results in a phenolic acid-rich fraction termed Water-Soluble Palm Fruit Extract (WSPFE). Pre-clinical in vitro, ex vivo, and in vivo studies carried out using various biological models have shown that WSPFE has beneficial bioactive properties, while clinical studies in healthy volunteers showed that it is safe for human consumption and confers antioxidant and anti-inflammatory effects. The composition, biological properties, and relevant molecular mechanisms of WSPFE discovered thus far are discussed in the present review, with a view to offer future research perspectives on WSPFE for health and non-health applications.
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Background Influenza is an acute respiratory tract infection caused by the influenza virus. Vaccination and antiviral drugs are the two methods opted to control the disease. Besides their efficiency, they also cause adverse side effects. Hence, scientists turned their attention to powerful herbal medicines. This review put focus on various proven, scientifically validated anti-influenza compounds produced by the plants suggested for the production of newer drugs for the better treatment of influenza and its related antiviral diseases too. Main body In this review, fifty medicinal herb phytochemical constituents and their anti-influenza activities have been documented. Specifically, this review brings out the accurate and substantiates mechanisms of action of these constituents. This study categorizes the phytochemical constituents into primary and secondary metabolites which provide a source for synthesizing and developing new drugs. Conclusion This article provides a summary of the actions of the herbal constituents. Since the mechanisms of action of the components are elucidated, the pandemic situation arising due to influenza and similar antiviral diseases can be handled promisingly with greater efficiency. However, clinical trials are in great demand. The formulation of usage may be a single drug compound or multi-herbal combination. These, in turn, open up a new arena for the pharmaceutical industries to develop innovative drugs.
Article
In this work, a surface molecular imprinted polymers (MIPs)-based boronate affinity adsorbent was prepared on dendritic fibrous silica particle (DFSP) for rapid recognition and selective separation of shikimic acid for the first time. Double recognition of both imprinted cavity and boronate affinity endowing the MIPs material high adsorption capacity and superior selectivity, which could reach 43.708 mg g⁻¹ at 308 K and pH 8, relatively higher than other reported materials. In addition, pH response adsorption towards SA was achieved in the work. Under the optimum condition, the experimental kinetics data is confirmed to the pseudo-second order model (R² =0.9957), and the adsorption process of shikimic acid is well fitted with the Langmuir model (R² >0.99). In contrast, the adsorption quantity of MIPs based adsorbent was 3.75 times higher than that of non-imprinted samples. Moreover, the as-obtained MIPs showed comparable reusability after five cycles of continuous adsorption-desorption, which maintained 86.38% of the initial adsorption quantity. The enhanced selectivity property and good regeneration performance makes the boronate affinity MIPs a promising and practical material for rapid recognition and specific capture of shikimic acid. Therefore, the strategy posed in this work sheds new light on the role of boronate affinity MIPs in the adsorption of shikimic acid.
Article
Up to now, extraction of shikimic acid (SA), precursor of antiviral drugs, from the surrounding plants is the most effective and sustainable methods. However, it’s still a tough challenge to obtain high purity SA due to the complex components in the plant issue. In this study, based on the specific identification of boronate affinity, iron hydroxide oxide FeOOH with abundant functional groups was used as the substrate to prepare molecular imprinted polymers ([email protected]) for selective recognition and adsorption of SA. Using 4-vinylphenylboronic acid (VPBA) as functional monomer, the imprinted polymers were prepared by the controllable directional surface imprinting method. FT-IR analysis and XPS study confirmed the characteristic structure and component of the products. From the results from the batch mode experiments, the maximum adsorption capacity of shikimic acid by [email protected] can reach 42.919 mg g⁻¹, which was enhanced compared with nonimprinted products. In addition, the adsorption process was well fitted with Langmuir isotherm model and pseudo-second-order model, implying the chemisorption of SA onto [email protected] through the monolayer. The investigation on pH factor showed that the adsorption amount towards SA was increased and then declined with the increase of pH value in the surrounding solution, attributing to the feature of boronate affinity effect. More importantly, it was found that the adsorbent exhibited competitive reusability performance. [email protected] maintained 86.45% of the first cycle adsorption capacity towards SA after 5 cycles, giving a reasonable proof for the feasible application of the products in the separation of substances containing the special structure of cis-diol.
Chapter
An influenza pandemic can have devastating effect on world populations and is a global concern. With the emergence of Fujian flu, caused by a mutation of the H5N1 strain of avian flu (A type) in 2004–2005, it quickly became apparent that, in the face of this new and virulent virus, resistant to known treatments and with a high potential for further mutation, new defensive medicinal weaponry was needed. Among the large number of compounds produced, Zanamivir and Oseltamivir emerged as forerunners. This chapter illustrates how research carried out in the pharmaceutical industry towards the production of the active pharmaceutical ingredient and worldwide sales of the finished drug product of Oseltamivir evolved. It discusses the retrosynthetic analysis, first reported synthesis and the industrial chemical syntheses of Oseltamivir. Both shikimic and quinic acids are structurally close to the drug substance making a semi‐synthesis from either an excellent choice for implementation on a large scale.
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Novel enzymes and novel enzymatic pathways for the pyruvate-based synthesis of shikimate or at least one intermediate thereto or derivative thereof, nucleic acids encoding the enzymes, cells transformed therewith, and kits containing said enzymes, cells, or nucleic acid. A KDPGal aldolase is used to perform condensation of pyruvate with D-erythrose 4-phosphate to form 3-deoxy-D-arabino-heptulosonate-7-phosphate (DAHP); a 3-dehydroquinate synthase is used to convert the DAHP to 3-dehydroquinate (DHQ); DHQ dehydratase can then convert DHQ to the key shikimate intermediate, 3-dehydroshikimate.
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A GC-MS procedure is described for the simultaneous quantitatation of the minor and major constituents of honeys, as their trimethylsilyl derivatives, from one solution, by one injection. Selected minor components (aliphatic and aromatic carboxylic acids, members of various homologous series, together with o-phosphoric acid, proline and hydroxymethylfurfurol), have been determined on the basis of their characteristic fragment ions, in the presence of extremely high excess of honeysaccharides. Selective fragmentation of these minor compounds in the ion trap detector provided possibilities for distinguishing them. The method permitted the simultaneous quantitation of o-phosphoric, malic, shikimic, citric/isocitric, quinic, margaric, oleic and stearic acids, hydroxymethylfurfurol and proline with the extremely high sugar contents of honeys (fructose, glucose, galacturonic acid, inositol, sucrose, trehalose, turanose, maltose, gentiobiose, isomaltose, raffinose, erlose, melezitose, maltotriose, panose, isomaltotriose) and allowed the fast evaluation of sugar and acid constituents of fifteen honeys from various floral and geological origin. Results revealed that (i) the minor components varied in the concentration range of 0.0001 to 0.43%, and, (ii) together with the saccharides of honeys made up the total of identified and determined constituents from 87.8% to 98.5%. Quantitative evaluation of the minor constituents was performed on the basis of their selective fragment ion values with an average reproducibility of 6.7% (RSD).
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We have been further studying on the specific lignification in the gourd fruits as shown in the previous paper. During the process of lignification, the both activities of peroxidase and β-glucosidase were decreased, and so were shikimic acid, while some organic acids including quinic acid were detected by paper chromatography.
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In the previous papers1)2)3), we have demonstrated the distribution of shikimic acid in Bryophyta and Pteridophyta and in the leaves of coniferous, monocotyledonous and dictotyle-donous plants, and we showed the contents of this acid in the organs of several plants.
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In 2002, the University of Wisconsin (UW) Internships in Public Science Education (IPSE) program started as a way to connect audiences of all ages to scientific expertise and cutting-edge research that might not otherwise be available to them. Graduate and undergraduate interns designed hands-on, interactive activities that use basic science concepts to explain cutting-edge nanotechnology concepts. To date, the collaboration has resulted in an innovative program using the strengths of each partner to bring cutting-edge science to the public. In the process, the interns received technical training and engaged in an iterative project development process as they gained experience in communicating science; the public developed a better understanding of and appreciation for nanoscale science, technology, and engineering.
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Heating shikimic acid in near-critical water leads to the formation of phenol. Since shikimic acid can now be obtained by the microbial conversion of glucose, a benzene-freer route to phenol could become an alternative to the industrial Hock oxidation of cumene derived from benzene (see scheme).
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The higher activities were obtained at pH 4.8 and 5.4 in the crude enzyme of peroxidase and inhibited by potassium cyanide. β-glucosi-dase was present and its opt. pH was 4.8. Laccase was scarcely found in the fruits. Some organic acids were detected by paper chromato-graphy; succinic, malic, citric, tartaric, quinic and shikimic acids. Especially, both enzymes and shikimic acid were shown to decrease with proceeding of lignification.
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A homologous series of (-)-shikimic acid gallates (I-V) has been isolated, together with 1, 6-di-O-galloyl-β-D-glucopyranoside (VI), 5-O-galloyl-D-hamamelose (VII), 2, 5-di-O-galloyl-D-hamamelose (VIII) and 2', 3, 5-tri-O-galloyl-D-hamamelose (IX), from the leaves of Castanopsis cuspidata var. sieboldii NAKAI. On the basis of spectroscopic analysis, enzymatic hydrolysis and methanolysis, their structures have been established as 3-O-gallate (I), 3-O-digallate (II), 3-O-trigallate (III), 3, 5-di-O-gallate (IV) and 3, 4-di-O-gallate (V) of (-)-shikimic acid.
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Four lignans, blechnic acid (1), 7-epiblechnic acid (3), 8-epiblechnic acid (6) and brainic acid (2), were isolated from six Blechnaceous ferns, Blechnum orientale, Struthiopteris amabilis, S. niponica, Woodwardia orientalis, W. prolifera and Brainea insignis. Their structures were determined by spectroscopic methods and chemical conversion.
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A method for the separation of phenolic acids along with shikimic and quinic acids by means of capillary gas chromatography is described and discussed. The method involves the previous derivatization of the acids to trimethylsilyl derivatives and it has been applied to the separation of acids extracted from olive leaves and roots, elm leaves and a soil A horizon. Quite good results were achieved both from qualitative and quantitative points of view. Qualitative differences have been pointed out in the phenolic acid composition of two olive cultivars and between leaves and roots of the same cultivar; also two elm species can be discriminated on the basis of the phenolic acid content.
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The synthesis of 3-2H- and 4-2H--shikimic acids was accomplished starting from commercially available -shikimic acid.
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FOLLOWING the discovery of quinic acid in apple fruits1 it has been found in other fruits2,3 and in grass4. It was originally suggested that quinic acid might provide a link between aliphatic and aromatic metabolism in plants, and that shikimic acid might be the first stage from quinic acid in the `disaturation' of the six-membered carbon ring1. However, shikimic acid could not at that time be found in apples. It was, however, isolated later from grass5 and has recently been detected in small amounts in the juice of cider apples by Phillips, Pollard and Whiting6, who used paper chromatography and a specific colour reaction. The development of the technique of gradient elution of organic acids from anion exchange resins7,8 has greatly facilitated the separation and isolation in the pure state of organic acids present in very small amount from solutions which also contain other acids in much larger quantity; by using this technique, an acid has now been found in very small amount on paper chromatograms prepared from extracts of the peel of Bramley's Seedling apples which gave a yellow to orange colour with Cartwright and Roberts reagent9 (specific for quinic, shikimic and dihydroshikimic acids6) and corresponded in RMalic values with shikimic acid. About 20 mgm. of this acid was obtained in the pure form from an extract of 300 gm. of the peel of the same apples using gradient elution (acetic acid) from `Dowex 1' columns in the acetate form. The acid had a specific rotation of [alpha]20D =-177.5° (an authentic sample, measured at the same concentration, of shikimic acid kindly supplied by Dr. Wayne Umbreit of the Merck Institute, gave [alpha]0D = -177.1°). The elementary analysis gave, C, 46.9; H, 5.8 per cent; calculated for shikimic acid C, 48.3; H, 5.79 per cent. The specimen had a melting point of 182.5° C. (corrected); mixed melting point with the Merck sample of shikimic acid, 183.5° C. (corrected). It was undoubtedly shikimic acid.
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The Diels-Alder adduct derived from trans-trans-1,4-diacetoxybutadiene and acrylic acid has been elaborated to D-(-)-shikimic acid. An alternative route is also discussed.
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The Knoevenagel condensation and intramolecular olefination have been successfully exploited in a novel synthesis of shikimic acid 1 and its phosphonate analogue 2 from D-lyxose 5-aldehyde 7.
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A laboratory experiment is outlined in which in the process of extracting shikimic acid from star aniseed exposes students to a number of important experimental techniques. The experimental procedure is designed to be carried out in a time period suitable for most undergraduate courses and is appropriate for both organic and natural product courses.
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3-Deoxy-3,3-difluoroshikimic acid 2 and its 4-epimer 3 as new analogues of shikimic acid have been synthesised from quinic acid in overall yields of 30% and 12%, respectively.
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The first successful method for the introduction of nitrogenous functionality at C-3 of the shikimate nucleus has been developed and has allowed the synthesis of (−)-3(R)-amino-4(R),5(R)-dihydroxy-1-cyclohexene-1-carboxylic acid [the 3(R)-amino analogue of (−)-shikimic acid] in seven steps from the parent acid.
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Quantitative determinations of quinic, shikimic and glycolic acide have been performed by reversed-phase high-performance liquid chormatography using p-bromophenacyl bromide as a visualizing reagent. The reactions are carried out in N,N-dimethylformamide (DMF) with KF as a catalyst. Linear calibration curves are obtained in the concentration range 0.1–2 mg acide per ml DMF. Spectroscopic and chromatographic properties of the pbromophenacyl bromide derivatives of quinic, shikimic, dehydroshikimic and glycolic acid are given. A quantitative analysis of quinic acid in plant material is demonstrated.
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The paper chromatography of phenols (expecially phenolic acids), aglycones, glycosides and certain sugars is carried out with two new solvents. The authors have also examined these substances with the aid of paper electrophoresis and a borate buffer. A detection reagent for o-diphenols on paper is described.
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An isolation procedure is presented that yields 2.4–3.7% w/w pure shikimic acid from the seeds of Liquidambar styraciflua (Sweetgum). Shikimic acid, the starting material in the commercial synthesis of the antiviral agent oseltamivir and an important intermediate in the biosynthesis of aromatic amino acids in plants, was found by HPLC to be abundant in the granular, aborted seeds (6.5% w/w) while present only in small amounts in the developed, fertile seeds (0.14% w/w). This extraction technique makes L. styraciflua, which is found in 40 states of the continental US, a potential renewable source of this important natural product.
Article
Sucrose, raffinose, pinitol, shikimic acid, and pungenin were isolated in crystalline form from leafy twigs of both Colorado spruce (Picea pungens Engelm.) and white spruce (Picea glauca (Moench) Voss) collected in winter. Raffinose and sucrose were the main sugars present in winter but raffinose disappeared in early spring and was not found again until autumn. Pungenin was also found in lowered concentrations in summer, and pinitol could not be crystallized from material collected in warm weather.Leafy twigs were harvested at different seasons and allowed to photosynthesize in the presence of C14O2 under constant conditions in the laboratory. Winter twigs were found to be convenient and efficient for the preparative biosynthesis of sucrose-C14 and raffinose-C14. Hemicellulose was labelled much more rapidly than cellulose. The C14 in the hemicellulose was concentrated in the glucose, little being found in the xylose.The relative rates of labelling of the sugars, pinitol, shikimic acid, pungenin, cellulose, and lignin showed some marked seasonal changes.
Article
SHIKIMIC, quinic, succinic, malic, citric, fumaric and lactic acids have been separated on `Dowex ]' ion-exchanger from combined aqueous and alcohol extracts of Iris pseudacorus, using the method of Hulme and Wooltorton1. These acids have been identified from their elution positions, their RF values in various solvents and by chemical tests where appropriate.
Article
IN a recent survey of the organic acids of fruits, shikimic acid has heen found in considerable amount in each of the varieties of gooseberry examined. Aqueous extracts of unripe fruits of the varieties Leveller, Careless and Whinham's Industry, after precipitation of pectin with 60 per cent acetone, were investigated by paper chromatography using the following three solvents: (1) benzyl alcohol–iso-propyl alcohol – tert.-butyl alcohol – water – formic acid (3:1:1:1:2 per cent)1, (2) n-propyl alcohol – cone. ammonia (70:30)2, (3) phenol – water – formic acid (3:1:1 per cent)1. In addition to malic and citric acid spots, a third spot (A) was observed with RF values in solvents (2) and (3), 0.17 and 0.58 respectively, identical with those of shikimic acid; citric acid and shikimic acid do not separate in solvent (1). Spot A separated from quinic and dihydroshikimic acids in solvent (3)3, RF values 0.58, 0.50 and 0.66 respectively, and rapidly gave a greenish-yellow colour at room temperature on spraying with sodium metaperiodate followed by sodium nitroprusside and piperazine4. This reagent is so far only known to give a reaction with quinic, shikimic and dihydroshikimic acids3. It has now been found that shikimic acid reacts at room temperature within a few minutes, while the other acids react more slowly. This observation is an additional aid to identification.
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The highly enantioselective Diels-Alder reaction between acryloyl oxazolidinone and furan, catalyzed by cationic bis(4-tert-butyloxazoline)Cu(II) complex 1, is presented. Though the reaction equilibrates rapidly at −20 °C, reaction at −78 °C permits isolation of the kinetic product mixture. The synthetic utility of the reaction is demonstrated by the conversion of the cycloadduct to ent-shikimic acid.
Article
Thirty-eight compounds were isolated from the roots and stem bark of Piptostigma fugax, besides three fractions of mixtures of homologues of two 6′-acylated sterol glucosides and fatty acids, respectively. Structures were determined by spectroscopic and chemical methods. Mixtures of homologues were analysed by GC-mass spectrometry after derivatization. 5α-Cycloart-24-ene-3β,16β,21-triol, 4-hydroxy-4,7-dimethyl-1-tetralone and three onychine-type alkaloids (2,7-dihydroxyonychine, 7-hydroxy-2-methoxyonychine and 7-hydroxy-2,8-dimethoxyonychine) represent new compounds. N-Methylheteropsine has been isolated as a natural product for the first time.
Article
Several α,β-unsaturated carboxylic acids show anomalous rotatory dispersion and circular dichroism at relatively long wave lengths (∼250-270 mμ). This finding necessitates the assumption that hitherto undetected very weak bands exist in the absorption spectra of these compounds; one such band is actually observed in the vapor spectrum of β,β-dimethylacrylic acid. Similar Cotton effects are also given by the sodium salt of one of the acids, and by several α,β-unsaturated lactones. In the case of shikimic acid (I), the expected circular dichroism is found, but the corresponding anomalous rotatory dispersion is completely obscured by background effects.
Article
A short total synthesis of shikimic acid and related derivatives is described in which an unusual, stereoselective Bu3SnD denomination conveniently furnishes 6β-deuterioshikimate for biosynthetic studies.
Article
A precursor of shikimic acid in the biosynthesis of five aromatic metabolites has been isolated from culture filtrates of a mutant strain of Escherichia coli. It has been characterized as a previously unknown unsaturated dihydroxy-monoketocarboxylic acid containing seven carbon atoms. Its formulation as 5-dehydro-shikimic acid is discussed.
Article
A stereospecific synthesis of dl-shikimic acid (I) from the Diels-Alder adduct of trans,trans-1,4-diacetoxy-1,3-butadiene (II) and methyl acrylate is reported. The optical resolution also was effected.
Article
Addition of hydrogen cyanide to (3R,5R)-3,4,5-triacetoxycyclohexanone (2) proceeded nonstereo-specifically to yield a 40:60 mixture of the two cyanohydrin epimers (1RS,3R,4S,5R)-1-hydroxy-5/3,4-triacetoxycyclohexane-1-carbonitrile (4), characterized as tetraacetates 5 and 6. Dehydration of cyanohydrins 4 under various conditions gave in equal proportions nitriles 9 and 10. arising from the two possible modes of elimination. The corresponding (-)-shikimic acid (11) and (-)-4-epi-shikimic acid (12) were then obtained from nitriles 9 and 10, respectively, by hydrolysis. (-)-4-epi-Shikimic acid [12,(3R,4R,5R)-3,4,5-tnhydroxy-1-cyclohexene-1-carboxylic acid] was completely characterized and compared with racemic 12 prepared by hydrogen fiuoride epimerization of methyl (-)-triacetylshikimate (15). Also, the shikimate and 4-epi-shikimate methyl esters (15 and 16) were shown to yield the same dihydro product, methyl (1R,3R,4S,5R)-3,4,5-triacetoxycyclohexane-1-carboxylate (18), thereby verifying the functional stereochemistry assigned to 12. Similarly, dehydration of methyl 3,4,5-tribenzoyl- and 3,4,5-triacetylquinate (20a,b) proceeded nonstereospecifically but predominately to shikimate esters. On the other hand, methyl 3,4,5-triacetyl-epi-quinate (22), prepared via HF epimerization of methyl 1,3,4,5-tetraacetylquinate (19), yielded as the major product upon dehydration the 4-epi-shikimate ester 16. The implications of these interconversions for quinate-shikimate chemistry are discussed.
Article
This method is useful for the rapid separation and tentative identification of carbohydrates and related compounds in biological fluids and extracts. No desalting or other purification is required. Interference by inorganic salts is prevented by a simple "overspotting" technique using pyridinium sulfate. Ascending one-dimensional chromatograms are completed in 2 hours. Spots of carbohydrates, polyhydric alcohols, aldonic and uronic acids, nucleosides, phosphate esters, and other derivatives are semiquantitatively detected by improved specific color reagents. Rf values are highly reproducible; this makes possible an analysis of some of the causes of variation in Rf, especially the systematic variations due to interference by inorganic ions and to varying loads. The method is not suitable for the complete separation of structurally similar carbohydrates or of a large number of carbohydrates and closely related compounds on one chromatogram; it is designed for the rapid identification of a small number of carbohydrates in complex biological systems containing considerable quantities of many other materials.
Article
Shikimic acid is used as a precursor for the synthesis of oseltamivir phosphate (Tamiflu®), which is used as an anti-viral for the H5N1 strain. As concern for this virus increases, demand for medicinal products capable of treating it increases, while shikimic acid resources remain limited. In this study, for the first time shikimic acid is extracted from pine needles using water at relatively low temperature. After the subsequent evaporation, column adsorption/desorption and crystallization processes, shikimic acid crystals with a purity of over 98 % are obtained. A total recovery of approximately 85 % is reached, with the highlights of the method being simplicity, low cost and industrial practicality.