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Folic acid belongs to the group of water-soluble B vitamins and naturally exists in multiple forms in a wide variety of foods such as legumes, vegetables, liver, and milk (Iyer and Tomar, 2009; Lyon et al., 2020). It is involved in many biochemical reactions critical for cell division, such as purine and pyrimidine biosynthesis, DNA/RNA biosynthesis, and amino acid metabolism (Iyer and Tomar, 2009). Mammals cannot synthesize folic acid and thus they must acquire it from food. Although folic acid is ubiquitous in foods, folic acid deficiency still often occurs due to various causes such as unhealthy diet (Hildebrand et al., 2021; Iimura et al., 2022), disease-related malabsorption (Arcot and Shrestha, 2005), medication-related depletion (Arcot and Shrestha, 2005), or vitamin B12 deficiency (Fishman et al., 2000). Folic acid deficiency has been associated with several health problems, such as anemia (Carmel, 2005; Bailey and Caudill, 2012), cancer (Duthie, 1999), cardiovascular diseases (Wald et al., 2002), neural tube defects in newborns (van der Put et al., 2001), neuropsychiatric dysfunction (Shea et al., 2002), depression (Falade et al., 2021), inflammatory diseases (Suzuki and Kunisawa, 2015; Jones et al., 2019), and eye diseases (Sijilmassi, 2019). To prevent folic acid deficiency, its daily intake (400 μg/d) has been recommended for adults in the European Union, and its increased intake (600 μg/d) is advised for women before and during pregnancy (FAO/WHO, 2002; IOM, 2004). The New Zealand government mandated the fortification of non-organic wheat flour with folic acid in July 2021, and the UK government mandated the fortification of non-wholemeal wheat flour with folic acid in September 2021 (Haggarty, 2021).

Perfluorooctane sulfonyl fluoride (PFOSF) has been defined as persistent organic pollutant in the Stockholm Convention in 2009. Currently PFOSF and its substitutes (structural analogues in which octyl group is substituted for other aliphatic chains) are still scarcely studied. HSA is a main carrier for drugs in blood, and the influence of exogenous compounds including pollutants on HSA is of particular interest. In this work, the binding sites of HSA to Perfluoroalkane sulfonyl fluoride (PFASFs) were determined by fluorescence technique. The results demonstrated that PFASFs competitively bind to HSA at Sudlow’s site I against warfarin and at Sudlow’s site II against dansyl-proline and the related association constants were determined. The association constants of PFOSF, perfluorohexane sulfonyl fluoride (PFHSF) and perfluorobutane sulfonyl fluoride (PFBSF) were determined to be 2.59 × 10−3 μM-1, 4.65 × 10−3 μM-1 and 2.85 × 10−3 μM-1 at Sudlow’s site I and 8.68 × 10−4 μM-1, 3.43 × 10−2 μM-1 and 1.92 × 10−2 μM-1 at Sudlow’s site II, respectively. The results showed that PFASFs can bind tightly to HSA and thus migrate to all parts of the body through vascular system. Non-covalent interaction between HSA and PFASFs was confirmed with tryptic digestion experiment. The mass spectra results indicated that other binding sites of HSA are also involved in the binding of PFHSF and PFBSF. The total binding numbers of PFOSF, PFHSF and PFBSF on HSA are 2, 6 and 3, respectively.

Resveratrol is a well-studied natural small molecule that possesses diverse bioactivities. Chemical derivation based on the resveratrol scaffold is of great importance to overcome the drawbacks of resveratrol and to improve its therapeutic potential. Continuous efforts have been established to develop resveratrol derivatives that target different therapeutic applications. Areas covered: This review covers patents published from 2012 to 2015. All resveratrol derivatives discussed are classified based on its derivation strategy as simple derivatives, conjugated derivatives and miscellaneous derivatives. Their therapeutic related activities are reviewed and discussed. Expert opinion: Chemical derivation is an effective strategy to enhance the benefits of resveratrol and ameliorate its disadvantages. Recent studies on resveratrol derivatives have made great progress in the treatment of cancer and neurodegenerative diseases to name a few, demonstrating improved activity compared with resveratrol. Notably, its bioavailability was also improved in some cases. However, the 'next generation' of resveratrol derivatives still requires the development of new strategies and techniques.

The polar compounds such as alkaloid compounds are important bioactive components in traditional Chinese medicines. In present study, a comprehensive method for separation and analysis of polar compounds from the polar fraction of traditional Chinese medicine Stephania yunnanensis was established. Both the major components and minor components were analyzed by counter-current chromatography combined with liquid chromatography tandem mass spectrometry (LC-MS(n)). From 50 mg polar fraction of crude extract, 15.2mg corydine and 4.8 mg stepharine with purities over 90% were successfully separated via a polar solvent system n-butanol: methanol: water (4:1:5, v/v) with 10 mM NaOH as an additive in the lower phase, in one step operation. Their structures were further identified by 1H NMR and FTICR-MS. Besides, three minor components were identified by HPLC-MS(n) based on the fragmentation behavior of the purified compounds.

An on-line column-switching counter-current chromatography (CCC) with solid-phase trapping interphase is presented in this paper. The large volume injection is avoided using solid-phase trapping interphase. Thereby, totally different chemical composition biphasic solvent system can be utilized to enhance system orthogonality. In the present work, a 140 mL-capacity CCC instrument was used in the first dimension, and a parallel three-coil CCC centrifuge (40 mL each coil) was used in the second dimensional separation allowing three injections at the same time. With biphasic solvent system composed of n-hexane: ethyl acetate: methanol: water (1:1:1:1, v/v), five well-separated fractions were obtained in the first dimension. Two fractions were online concentrated and further separated in the second dimension with solvent system composed of methyl tert-butyl ether: acetonitrile: water (2:2:3, v/v), where trifluoroacetic acid (10 mM) was added to the upper organic phase as a retainer and triethylamine (10 mM) to the aqueous mobile phase as an eluter. Four hydroxyanthraquinones were successfully separated and purified from Chinese medicinal plant Rheum officinale in only one step.

In order to investigate the antioxidant properties of the polysaccharides from the brown alga Sargassum fusiforme, the crude polysaccharides from S. fusiforme (SFPS) were extracted in hot water, and the lipid peroxidation inhibition assay exhibited that SFPS possessed a potential antioxidant activity. Hence, two purely polymeric fractions, SFPS-1 and SFPS-2 were isolated by the column of DEAE (2-diethylaminoethanol)-Sepharose Fast Flow, with their molecular weights of 51.4 and 30.3 kDa determined by high performance gel permeation chromatography (HPGPC). They were preliminarily characterized using chemical analysis in combination of infrared (IR) and nuclear magnetic resonance (NMR) spectroscopies and found to contain large amounts of uronic acids and beta-glycosidical linkages. The antioxidant activities of these two SFPS fractions were evaluated using superoxide and hydroxyl radical-scavenging assays. The results show that the antioxidant ability of SFPS-2 was higher than that of SFPS-1, probably correlating with the molecular weight and uronic acid content.

Two trace impurities in the bulk drug lisinopril were detected by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) with a simple and sensitive method suitable for HPLC/MSn analysis. The fragmentation behavior of lisinopril and the impurities was investigated, and two unknown impurities were elucidated as 2-(6-amino-1-(1-carboxyethylamino)-1-oxohexan-2-ylamino)-4-phenylbutanoic acid and 6-amino-2-(1-carboxy-3-phenylpro-pylamino)-hexanoic acid on the basis of the multi-stage mass spectrometry and exact mass evidence. The proposed structures of the two unknown impurities were further confirmed by nuclear magnetic resonance (NMR) experiments after preparative isolation.

Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient's lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin.

A two-dimensional counter-current chromatographic system (2D-CCC) for preparative isolation and purification of three prenylflavonoids from Artocarpus altilis is presented. An upright CCC instrument (CCC1, total capacity: 1600 ml) was used as the first dimension. Effluent of interest from CCC1 was collected on-line into a 30 ml sample loop by a laboratory-prepared column-switching interface and introduced into a high-speed CCC instrument (CCC2, total capacity: 210 ml) for the second dimension separation. With this 2D-CCC system and a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water (5:5:7:3 and 5:5:6.5:3.5, v/v/v/v), which had been selected by high-speed CCC, about a 500 mg amount of the crude extract was separated, yielding 9 mg of compound 1, 28 mg of compound 2 and 78 mg of compound 3. The purities of the three prenylflavonoids were 98.7 (1), 98.3 (2) and 97.2% (3), respectively, as determined by HPLC analysis. Their chemical structures were identified by electrospray ionization MS, (1)H NMR and (13)C NMR.

An impurity in the bulk drug lisinopril was detected by simple reversed-phase high-performance liquid chromatography (HPLC). This trace-level impurity was rapidly identified as 2-(2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid on the basis of the on-line multi-stage mass spectrometric evidence and the proposed structure was further confirmed by multi-stage mass spectrometry of lisinopril and three related compounds.

Two phenylbutenoids, ( E )-4-(3′,4′-dimethoxyphenyl)but-3-enyl acetate and ( E )-4-(3′,4′-dimethoxyphenyl)but-1,3-diene, were separated from the rhizomes of Zingiber Cassumunar using a preparative upright counter-current chromatography (CCC). With a two-phase solvent system composed of light petroleum (b.p. 60–90 °C)–ethanol–diethyl ether–water (5:4:2:1, v/v), 150 mg of ( E )-4-(3′,4′-dimethoxyphenyl)but-3-enyl acetate and 175 mg of ( E )-4-(3′,′-dimethoxyphenyl)but-1,3-diene with the purity of 98.7 and 95.1%, respectively, were obtained from 600 mg of the crude sample of Z. Cassumunar in a single-step separation. Structures of these two compounds were identified by ESI-MS, 1 H NMR and 13 C NMR.

Preparative counter-current chromatography (CCC) purification of valrubicin (AD-32) from crude synthetic drug has been successfully performed for the first time using upright coil planet centrifuge with four multilayer coils connected in series with 1600 ml capacity. The two-phase system used was composed of light petroleum (bp 60–90 °C)–ethyl acetate–tetrachloromethane–methanol–water at an optimized volume ratio of 1:1:8:6:1. Target compound (1.2 g) with a purity of 99.88% was obtained from 1.5 g of crude synthetic drug with a purity 95.49% based on HPLC peak area percentage. Identification of the target compound was performed by electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance.

A simple and rapid method for the identification of Vinca alkaloids from a crude extract of Catharanthus roseus G. Don (Apocynaceae) by direct-injection electrospray ionisation (ESI) and tandem mass spectrometry (MS/MS) has been developed. The alkaloids vindoline, vindolidine, vincristine and vinblastine were evaluated in a commercial extract of C. roseus using this method. Catharanthine and its isomers 19S-vindolinine and vindolinine were detected in the commercial product by direct injection ESI/MS/MS and confirmed by preparation and by HPLC-ESI/MS. For the characterisation of different fragment fingerprints, ESI/MS/MS is a sensitive, rapid and convenient technique by which to identify some constituents in complex and mixed plant extracts.

A series of impurities, which were all of the same molecular formula, C17H33NO7, were obtained in the process of voglibose synthesis. After isolation and purification, four isomeric cyclitols were completely assigned by 2D NMR experiments. One of the compounds was established by single-crystal X-ray diffraction analysis as 5,6-dideoxy-5-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}-1-C-(methoxycycl ohexylmethyl)-D-epi-inositol. (C) 2004 Elsevier Ltd. All rights reserved.

Polysaccharides extracted from Libyan dates with hot water and 0.05 M NaOH were fractionated and purified by ion-exchange and gel-filtration chromatography. According to the methylation and hydrolysis analyses, the results indicate the D-glucan to be linear and to contain both (1-->3)- and (1-->4)-linkages. The anomeric NMR measurements confirm that the sugar residues are beta-glycosidically linked. This is the first report on the isolation of a neutral beta-D-glucan from dates.

A highly efficient and catalyst-free method for the synthesis of substituted thiourea derivatives is presented. The synthesis is performed through the reaction of thiazolidine-2-thiones with various amines in water. A sound number of thioureas with both unsymmetrical and symmetrical architectures have been obtained in good to excellent yields.

A Broensted acid catalyzed redox amination of indoline with aldehydes for the synthesis of N-alkylindoles (III) proceeds via intramolecular hydride transfer.

The hepatoprotective and antioxidant activities of the n-butanol extract of Rubus parvifolius L. (RPL), a widely used medicinal plant, were evaluated. Results demonstrated that RPL extract possessed pronounced hepatoprotective effects against carbon tetrachloride (CCl(4))-induced hepatic injury in mice, which was at least partially attributed to its strong antioxidant capacity. Treatment with RPL extract markedly attenuated the increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels caused by CCl(4) intoxication. It also significantly prevented the decrease in superoxide dismutase (SOD) activity and the increase in malondialdehyde (MDA) content of liver tissue. Meanwhile, histopathological changes of hepatic damage were also remarkably ameliorated. Phytochemical analysis based on high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) revealed the presence of various phenolic compounds, including caffeic acid conjugates, ellagic acid glycosides, and flavonol glycosides, which might be responsible for the hepatoprotective and antioxidant activities of RPL.

Two previously unknown resveratrol trimers named wilsonols A-B, as well as a resveratrol tetramer named wilsonol C, were isolated from Vitis wilsonae Veitch, together with 12 known oligostilbenes. Their chemical structures have been elucidated by detailed analyses of 1D and 2D NMR spectroscopic data, as well as chemical evidence obtained via either catalysis with HRP (horseradish peroxidase) and H(2)O(2) (hydrogen peroxide), acid, or UV irradiation. During the chemical processes, a biomimetic resveratrol tetramer named diviniferin B that has not been found in nature was obtained. These oligostilbenes showed potent scavenging abilities towards DPPH radicals and selective quenching effects on (1)O(2) radicals. Furthermore, the biogenetic transformations between the 16 oligostilbenes have been elaborated chemically to provide a comprehensive mechanism of the antioxidative defense system in this plant species.

A palladium-catalyzed domino Heck reaction and dealkylation for the preparation of 2-substituted indoles is described. This novel transformation is based on an intramolecular Heck reaction followed by dealkylation.

A preparative two-dimensional counter-current chromatographic system (2D-CCC) for simultaneous separation and purification of oridonin and ponicidin from the crude extract of Rabdosia rubescens was presented. It was based on the use of a high-speed CCC (HSCCC, total column volume V(c)=146ml) instrument in the first dimension (1st-D) and a preparative upright CCC (UCCC, V(c)=1500ml) column in the second dimension (2nd-D). The interface was a homemade column-switching system with a 50-ml sample loop. In this way, almost the whole interested region from the first dimension was transferred on-line to the second dimension for further separation. The use of a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water (1:5:1:5 and 3:5:3:5, v/v) in the two dimensions permitted the simultaneous separation of oridonin and ponicidin, making this 2D-CCC system with satisfactory resolution and peak capacity. During about 9h separation, two injections with about a 250mg amount of the crude extract for each, was accomplished using this 2D-CCC system, yielding 60mg of oridonin (1) and 10mg of ponicidin (2) all at a purity of over 95% as determined by HPLC analysis. Their chemical structures were identified by electrospray ionization (ESI) MS, (1)H NMR and (13)C NMR.

The volatile oil from the roots of Patrinia scabra Bunge was isolated by steam distillation, and separated into four major fractions (Fr. A-D) by means of column chromatography. A total of 39 compounds (1-39) were identified by GC/MS analysis, and evaluated for their in vitro cytotoxic activities against human ovarian carcinoma cells (HO-8910) and human hepatoma cells (Bel-7402) (Table 1). Fr. A showed the strongest inhibitory effect on HO-8910 (IC50 = 21 microg/ml) and Bel-7402 cells (16 mcirog/ml), whereas Fr. B was the least active (>100 microg/ml). By comparison of the constituents of the four fractions, we assume that the cytotoxicity of the volatile oil of P. scabra is mainly due to the lignans and azulenes, rather than to caryophyllene oxide I (18). Our results suggest that the volatile oil of P. scabra possesses potent and tumor-specific cytotoxicity, and could serve as a possible candidate for future cancer chemotherapy.

During the routine impurity profile of lisinopril bulk drug by HPLC (high-performance liquid chromatography), a potential impurity was detected. Using multidimensional NMR (nuclear magnetic resonance) technique, the trace-level impurity was unambiguously identified to be 2-(-2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid after isolation from lisinopril bulk drug by semi-preparative HPLC. Formation of the impurity was also discussed. To our knowledge, this is a novel impurity and not reported elsewhere.

The gravitational force exerts an important effect on the counter-current chromatography (CCC) and has been used to retain the stationary phase and improve the efficiency in the various CCC separations. This paper deals with the effect of gravitational force on type-J CCC, one of the most popular CCC methods by the mathematical analysis for the first time. The theoretical analyses reveal a close relationship between the effect of gravitational force, the placed orientation of type-J CCC apparatus, and the revolutional speed. Two placed orientations are more suitable for preparative CCC separation: one is common horizontal, and the other upright. Thus, there are three optimum conditions for type-J CCC separation, the first using horizontal apparatus at very low revolutional speed around 10 rpm in the gravitational filed, the second by use of upright apparatus at moderate revolutional speed around 100 rpm in the three-dimensional complex force field composed of centrifugal and orthogonal gravitational force, and the third employing the apparatus placed at any orientation including horizontal and upright CCC apparatus at high revolutional speed above 300 rpm in the centrifugal force field. Therefore, we should consider the effect of gravitation force on CCC at the selection of proper operational conditions according to properties of two immiscible phases, the desired revolutional speed and the parameters of apparatus in order to utilize efficiently the effect of gravitational force. These analyses and results will benefit to improve the efficiency of CCC separation, especially large-scale industrial preparation.

Preparative counter-current chromatography (CCC) isolation of liensinine and its analogues, isoliensinine and neferine from embryo of the seed of Nelumbo nucifera GAERTN. has been successfully performed for the first time using upright coil planet centrifuge with four multilayer coils connected in series with 1600 mL capacity. Two kinds of two-phase solvent systems were applied to preparative CCC isolation. The first was the system composed of light petroleum (b.p. 60-90 degrees C)-ethyl acetate-tetrachloromethane-chloroform-methanol-water (1:1:4:4:6:2, v/v) which was very suitable for fast and small-scale CCC isolation. The second was the system composed of ethyl acetate-tetrachloromethane-methanol-water (1:6:4:1, v/v), which was the optimum for large-scale CCC isolation. Using the first system, 1102 mg of the crude alkaloid was purified in one-step separation of 150 min, yielding 350 mg neferine, 100 mg isoliensinine and 95 mg liensinine with over 95% purity. While using the second solvent system, 5850 mg of the crude alkaloid was purified in one-step separation of 9 h, yielding 2545 mg neferine, 698 mg isoliensinine and 650 mg liensinine with over 97% purity. Structures of the compounds were identified by electrospray ionization multiple mass spectrometry, one- and two-dimensional NMR.

The stems of Hedychium villosum yielded the new diterpenoid 1, named villosin, along with coronarin E and beta-sitosterol. Their structures were elucidated by spectroscopic methods including mono- and bi-dimensional NMR.