Visible-Light-Promoted α-Benzylation of N-Phenyl α-Amino Acids to α-Amino Phenylpropanoids.

A new method for the synthesis of α-amino phenylpropanoids under blue light-emitting diode irradiation has been developed through α-C-H benzylation of readily available N-phenyl glycine ester with benzyl oxalates as a coupling partner under mild conditions. A range of N-phenyl glycine esters were successfully converted to α-amino phenylpropanoid products in moderate to good yields. The utility of this methodology is underlined by its application to the late-state modification of natural products.

Visible-Light-Promoted Biomimetic Reductive Functionalization of Quaternary Benzophenanthridine Alkaloids.

Reduction of an iminium C═N double bond is the most important phase I metabolism process associated with the cytotoxic property of quaternary benzophenanthridine alkaloids (QBAs). Inspired by the light-mediated reduction of QBAs with nicotinamide adenine dinucleotide, a visible-light-promoted reductive functionalization reaction of QBAs is reported in this study. C4-Alkyl-1,4-dihydropyridines (DHPs) enable the direct reductive alkylation of QBA independently, serving as both single-electron-transfer reductant reagents under irradiation with 455 nm blue light in the absence of photocatalysts and additional additives. Our protocol can be further applied to the semisynthesis of natural 6-substituted dihydrobenzophenanthridine derivatives such as O-acetyl maclekarpine E.

The levels of bioactive ingredients in Citrus aurantium L. at different harvest periods and antioxidant effects on H2 O2 -induced RIN-m5F cells.

BACKGROUND: Citrus aurantium L. (Aurantii fructus) is a multi-purpose citrus fruit with high medicinal and nutritional value, but currently there are no data that can be used to investigate the appropriate harvest time to obtain high-quality citrus bioactive ingredients from it. RESULTS: Phytochemicals and the levels of the main bioactive ingredients were investigated by ultra high performance liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-Q-TOF/MS). The flavanone, polymethoxyflavone, coumarin, synephrine, and limonin content in the citrus fruit was analyzed at different harvest periods, and significant differences, ranging from 0.03 ± 0.01 to 116.26 ± 40.20 g kg-1 (DW), were shown. These compounds were present in higher amounts in June and then decreased gradually, while the biomass accumulation of most of them showed an increasing tendency around harvest time. The H2 O2 -induced RIN-m5F cells model was employed to evaluate their antioxidant capacity. Citrus fruit harvested from June 11 to July 7 possessed an excellent antioxidant capacity by inhibiting the intensity of intracellular reactive oxygen species (ROS) (P < 0.01) and improving superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH) activity (P < 0.01). The chemical composition and antioxidant capacity of citrus leaves, stems, and roots were also evaluated, and these showed great variation compared with other citrus fruits. Multivariate statistical analysis indicated that harvesting time was related closely to the phytochemical contents and antioxidant capacity. CONCLUSION: Citrus fruit can be appropriately harvested from June to early July when the levels of bioactive ingredients and antioxidant activity reach higher values. This research provides practical information for producing high-quality citrus products. © 2020 Society of Chemical Industry.

Rapid Investigation and Screening of Bioactive Components in Simo Decoction via LC-Q-TOF-MS and UF-HPLC-MD Methods.

Simo decoction (SMD), as a traditional medicine, is widely used in the treatment of gastrointestinal dysmotility in China. In this study, a combined method of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) and ultrafiltration high-performance liquid chromatography molecular docking (UF-HPLC-MD) was efficiently employed to identify and screen bioactive ingredients in SMD. Ninety-four major constituents were identified or tentatively characterized by comparing their retention times and mass spectra with standards or literature data by using LC-Q-TOF-MS, and the ascription of those compounds were classified for the first time. Among them, 13 bioactive ingredients, including norisoboldine, eriocitrin, neoeriocitrin, narirutin, hesperidin, naringin, neohesperidin, hesperitin-7-O-glucoside, linderane, poncirin, costunolide, nobiletin, and tangeretin, were primarily identified as the human serum albumin (HSA) ligands at a range of docking scores from -29.7 to -40.6 kJ/mol by UF-HPLC-MD. The results indicate the systematic identification and screening of HSA ligands from Simo decoction guided by LC-Q-TOF-MS and UF-HPLC-MD represents a feasible and efficient method that could be extended for the identification and screening of other bioactive ingredients from natural medicines.

Chemical Profiles and Simultaneous Quantification of Aurantii fructus by Use of HPLC-Q-TOF-MS Combined with GC-MS and HPLC Methods.

Aurantii fructus (AF) is a traditional Chinese medicine that has been used to improve gastrointestinal motility disorders for over a thousand years, but there is no exhaustive identification of the basic chemical components and comprehensive quality control of this herb. In this study, high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS) and gas chromatography coupled mass spectrometry (GC-MS) were employed to identify the basic chemical compounds, and high-performance liquid chromatography (HPLC) was developed to determine the major biochemical markers from AF extract. There were 104 compounds belonging to eight structure types, including 13 amino acids or peptides, seven alkaloids, 18 flavanones, 14 flavones, 15 polymethoxyflavonoids, six triterpenoids, nine coumarins, and 18 volatile oils, as well as four other compounds that were systematically identified as the basic components from AF, and among them, 41 compounds were reported for the first time. Twelve bioactive ingredients were chosen as the benchmark markers to evaluate the quality of AF. The analysis was completed with a gradient elution at a flow rate of 0.7 mL/min within 55 min. This efficient method was validated showing good linearity, precision, stability, repeatability and recovery. Furthermore, the method was successfully applied to the simultaneous determination of 12 chemical markers in different samples of AF. This study could be applied to the identification of multiple bioactive substances and improve the quality control of AF.

Metal-Free Photoredox Catalyzed Cyclization of O-(2,4-Dinitrophenyl)oximes to Phenanthridines.

A metal-free visible-light photoredox-catalyzed intermolecular cyclization reaction of O-2,4-dinitrophenyl oximes to phenanthridines was developed. In this study, the organic dye eosin Y and i-Pr2NEt were used as photocatalyst and terminal reductant, respectively. The oxime substrates were transformed into iminyl radical intermediates by single-electron reduction, which then underwent intermolecular homolytic aromatic substitution (HAS) reactions to give phenanthridine derivatives.

Synthesis of 5-methyl phenanthridium derivatives: a new class of human DOPA decarboxylase inhibitors.

DOPA decarboxylase (DDC) is responsible for the decarboxylation of l-DOPA and related aromatic amino acids and correlates closely with a number of clinical disorders. Sanguinarine, a natural quaternary benzophenanthridine alkaloid (QBA), was reported to be inhibitor of rat DDC and possessed a different inhibitory mechanism. In this study, several natural QBAs were assayed as human DDC inhibitors for the first time. A series of 5-methyl phenanthridium derivatives that contain the basic core structure of QBAs were also synthesized and evaluated as human DDC inhibitors. The title compounds still possessed DDC inhibitory potential. Among the synthesized compounds, 2-hydroxyl-8-methoxy-5-methylphenanthridinium chloride (11k) showed good inhibitory activity with an IC50 value of 0.12mM. Preliminary structure-activity relationship indicated that DDC inhibitory potential of 5-methyl phenanthridium derivatives correlated with the π-electro densities on CN double bond of iminium cation. The hydroxyl group on compound 11k possibly contributed to the formation of hydrogen bond between DDC and the inhibitor.

Photoredox catalysed reductive aminomethylation of quaternary benzophenanthridine alkaloids.

Reduction of C = N double bond is the most important phase I metabolism process of quaternary benzophenanthridine alkaloids (QBAs). Inspired by the NADPH mediated reduction in QBAs, a visible-light promoted reductive aminomethylation of QBAs for synthesis of 6-substituted benzophenanthridines was reported using QBAs and N,N-dimethylaniline as coupling partners in this study. An α-amino radical that derived from QBAs was supposed to be the key intermediate in this visible-light promoted reductive aminomethylation reaction.

Visible-light-promoted and chlorophyll-catalyzed aerobic desulfurization of thioamides to amides.

A novel method for the metal-free synthesis of amides from thioamides based on visible-light photoredox catalysis and in an air atmosphere is reported. Natural pigment chlorophyll is used as a photosensitizer to generate singlet molecular oxygen 1O2, which is involved in the aerobic desulfurization of thioamides. The protocol provides amides in good yields at room temperature under mild conditions. On the basis of experimental results, a plausible photoredox mechanism is proposed.

Simultaneous quantitative determination of sanguinarine, chelerythrine, dihydrosanguinarine and dihydrochelerythrine in chicken by HPLC-MS/MS method and its applications to drug residue and pharmacokinetic study.

A specific and reliable HPLC-MS/MS method was developed and validated for simultaneously determination of sanguinarine, chelerythrine and their metabolites (dihydrosanguinarine and dihydrochelerythrine) in chicken tissue for the first time. This is important because these compounds are related to the use of a naturally occurring and novel feed additive with many benefits, but the levels of these compounds must be strictly controlled. The compounds were extracted by acetonitrile and 1% HCl-methanol solution successively and then separated on a C18 column. A triple-quadrupole mass spectrometer equipped with an electrospray ionization (ESI) source was used for detection. Quantification was performed using multiple reaction monitoring with positive mode. The method was validated in terms of specificity, linearity, precision, accuracy and stability. The calibration curves were linear over the concentration range of 0.5-100.0ng/g for sanguinarine, 0.5-100.0ng/g for chelerythrine, 0.2-100.0ng/g for dihydrosanguinarine and 0.1-100ng/g for dihydrochelerythrine, respectively. All of the recovery rates of the four analytes were over 85%. The RSD of intra-day and inter-day precision was less than 5.0%, and the relative error was all within 12.0%. This validated method has been successfully applied to assess the drug residue and metabolite residue characteristics of sanguinarine and chelerythrine in chicken tissue after oral administration of the extracts of Macleaya cordata (Willd.) R. Br, and to investigate the pharmacokinetic parameters of sanguinarine and dihydrosanguinarine in chicken plasma.

Alizarin violet modified carbon paste electrode for the determination of trace silver(I) by adsorptive voltammetry.

A sensitive and selective procedure for the determination of trace silver(I) at alizarin violet modified carbon paste electrode has been developed. Silver(I) was accumulated on the electrode surface via complex formation with modifier in 0.1mol/L acetate buffer (pH 5.2). After electrochemical reduction of silver(I) had been carried out, the reoxidation wave of silver(0) appeared at 0.05V (versus SCE) on scanning the potential in the positive direction in 0.1mol/L H(2)SO(4)+2.0x10(-4)mol/L KBr. For a preconcentration time of 3min, the detection limit is 1.0x10(-10)mol/L and the linear range is from 3.0x10(-10) to 1.2x10(-7)mol/L. Many coexisting metal ions have little or no effect on the determination of silver(I). The proposed method was applied to the determination of silver in waste water and zinc alloy samples with satisfactory results.