Validation of a High-Performance Liquid Chromatography with Photodiode Array Detection Method for the Separation and Quantification of Antioxidant and Skin Anti-Aging Flavonoids from Nelumbo nucifera Gaertn. Stamen Extract

Nelumbo nucifera Gaertn., or the so-called sacred lotus, is a useful aquatic plant in the Nelumbonaceae family that has long been used to prepare teas, traditional medicines as well as foods. Many studies reported on the phytochemicals and biological activities of its leaves and seeds. However, to date, only few studies were conducted on its stamen, which is the most important ingredient for herbal medicines, teas and other phytopharmaceutical products. Thus, this present study focuses on the following: (1) the application of high-performance liquid chromatography with photodiode array detection for a validated separation and quantification of flavonoids from stamen; (2) the Nelumbo nucifera stamen’s in vitro and in cellulo antioxidant activities; as well as (3) its potential regarding the inhibition of skin aging enzymes for cosmetic applications. The optimal separation of the main flavonoids from the stamen ethanolic extract was effectively achieved using a core-shell column. The results indicated that stamen ethanolic extract has higher concentration of in vitro and in cellulo antioxidant flavonoids than other floral components. Stamen ethanolic extract showed the highest protective effect against reactive oxygen/nitrogen species formation, as confirmed by cellular antioxidant assay using a yeast model. The evaluation of potential skin anti-aging action showed that the stamen extract has higher potential to inhibit tyrosinase and collagenase compared with its whole flower. These current findings are the first report to suggest the possibility to employ N. nucifera stamen ethanolic extract as a tyrosinase and collagenase inhibitor in cosmetic applications, as well as the utility of the current separation method.     

Wittig and horner-wittig coupling reactions of 2-substituted cyclic ethers and their application to spiroketal synthesis

Wittig and Horner-Wittig coupling reactions of tetrahydropyran or tetrahydrofuran 2-triphenylphosphonium salts or 2-diphenylphosphine oxides with aldehydes and lactols affords good yields of the corresponding enol ethers. In selected examples these enol ether products may be further converted to spiroketals some of which are natural pheromones derived from $\text{Dacus oleae}$ and $\text{Paravespula vulgaris}$.     

An unusual dichotomy in the regioselectivity of a metal catalyzed versus thermal ene reaction

A Pd(+2) catalyzed cyclization of a 1,6-enyne complements a thermal Alder ene reaction; a rationale invoking a remote binding site is proposed.     

Development and Molecular Understanding of a Pd-Catalyzed Cyanation of Aryl Boronic Acids Enabled by High-Throughput Experimentation and Data Analysis

A synthetic method for the palladium-catalyzed cyanation of aryl boronic acids using bench stable and non-toxic N-cyanosuccinimide has been developed. High-throughput experimentation facilitated the screen of 90 different ligands and the resultant statistical data analysis identified that ligand σ-donation, π-acidity and sterics are key drivers that govern yield. Categorization into three ligand groups – monophosphines, bisphosphines and miscellaneous – was performed before the analysis. For the monophosphines, the yield of the reaction increases for strong σ-donating, weak π-accepting ligands, with flexible pendant substituents. For the bisphosphines, the yield predominantly correlates with ligand lability. The applicability of the designed reaction to a wider substrate scope was investigated, showing good functional group tolerance in particular with boronic acids bearing electron-withdrawing substituents. This work outlines the development of a novel reaction, coupled with a fast and efficient workflow to gain understanding of the optimal ligand properties for the design of improved palladium cross-coupling catalysts.     

Controlled Synthesis of Large Single Crystals of Metal-Organic Framework CPO-27-Ni Prepared by a Modulation Approach: In situ Single-Crystal X-ray Diffraction Studies

The size of single crystals of the metal-organic framework CPO-27-Ni was incrementally increased through a series of modulated syntheses. A novel linker modulated synthesis using 2,5-dihydroxyterephthalic acid and the isomeric ligand 4,6-dihydroxyisophthalic acid yielded large single crystals of CPO-27-Ni (∼70 μm). All materials were shown to have high crystallinity and phase purity through powder X-ray diffraction, electron microscopy methods, thermogravimetry, and compositional analysis. For the first time single-crystal structure analyses were carried out on CPO-27-Ni. High BET surface areas and nitric oxide (NO) release efficiencies were recorded for all materials. Large single crystals of CPO-27-Ni showed a prolonged NO release and proved suitable for in situ single-crystal diffraction experiments to follow the NO adsorption. An efficient activation protocol was developed, leading to a dehydrated structure after just 4 h, which subsequently was NO-loaded, leading to a first NO loaded single-crystal structural model of CPO-27-Ni.     

Inherent Ethyl Acetate Selectivity in a Trianglimine Molecular Solid

Ethyl acetate is an important chemical raw material and solvent. It is also a key volatile organic compound in the brewing industry and a marker for lung cancer. Materials that are highly selective toward ethyl acetate are needed for its separation and detection. Here, we report a trianglimine macrocycle ( TAMC ) that selectively adsorbs ethyl acetate by forming a solvate. Crystal structure prediction showed this to be the lowest energy solvate structure available. This solvate leaves a metastable, “templated” cavity after solvent removal. Adsorption and breakthrough experiments confirmed that TAMC has adequate adsorption kinetics to separate ethyl acetate from azeotropic mixtures with ethanol, which is a challenging and energy-intensive industrial separation.     

Scarlet Flax Linum grandiflorum (L.) In Vitro Cultures as a New Source of Antioxidant and Anti-Inflammatory Lignans

In vitro cultures of scarlet flax (Linum grandiflorum L.), an important ornamental flax, have been established as a new possible valuable resource of lignans and neolignans for antioxidant and anti-inflammatory applications. The callogenic potential at different concentrations of α-naphthalene acetic acid (NAA) and thidiazuron (TDZ), alone or in combinations, was evaluated using both L. grandiflorum hypocotyl and cotyledon explants. A higher callus induction frequency was observed on NAA than TDZ, especially for hypocotyl explants, with a maximum frequency (i.e., 95.2%) on 1.0 mg/L of NAA. The presence of NAA (1.0 mg/L) in conjunction with TDZ tended to increase the frequency of callogenesis relative to TDZ alone, but never reached the values observed with NAA alone, thereby indicating the lack of synergy between these two plant growth regulators (PGRs). Similarly, in terms of biomass, NAA was more effective than TDZ, with a maximum accumulation of biomass registered for medium supplemented with 1.0 mg/L of NAA using hypocotyls as initial explants (DW: 13.1 g). However, for biomass, a synergy between the two PGRs was observed, particularly for cotyledon-derived explants and for the lowest concentrations of TDZ. The influence of these two PGRs on callogenesis and biomass is discussed. The HPLC analysis confirmed the presence of lignans (secoisolariciresinol (SECO) and lariciresinol (LARI) and neolignan (dehydrodiconiferyl alcohol [DCA]) naturally accumulated in their glycoside forms. Furthermore, the antioxidant activities performed for both hypocotyl- and cotyledon-derived cultures were also found maximal (DPPH: 89.5%, FRAP 866: µM TEAC, ABTS: 456 µM TEAC) in hypocotyl-derived callus cultures as compared with callus obtained from cotyledon explants. Moreover, the anti-inflammatory activities revealed high inhibition (COX-1: 47.4% and COX-2: 51.1%) for extract of hypocotyl-derived callus cultures at 2.5 mg/L TDZ. The anti-inflammatory action against COX-1 and COX-2 was supported by the IC₅₀ values. This report provides a viable approach for enhanced biomass accumulation and efficient production of (neo)lignans in L. grandiflorum callus cultures.     

Palladium-catalyzed asymmetric allylic alkylation (AAA) with alkyl sulfones as nucleophiles

An efficient palladium-catalyzed AAA reaction with a simple α-sulfonyl carbon anion as nucleophiles is presented for the first time. Allyl fluorides are used as superior precursors for the generation of π-allyl complexes that upon ionization liberate fluoride anions for activation of silylated nucleophiles. With the unique bidentate diamidophosphite ligand ligated palladium as catalyst, the in situ generated α-sulfonyl carbon anion was quickly captured by the allylic intermediates, affording a series of chiral homo-allylic sulfones with high efficiency and selectivity. This work provides a mild in situ desilylation strategy to reveal nucleophilic carbon centers that could be used to overcome the pK_a limitation of “hard” nucleophiles in enantioselective transformations.

A variety of “hard” α-sulfonyl carbanions of aryl, heteroaryl and alkyl sulfones were successfully employed as nucleophiles in palladium-catalyzed asymmetric allylic alkylation with excellent enantioselectivities.     

Toward the development of new photolabile protecting groups that can rapidly release bioactive compounds upon photolysis with visible light

The synthesis and characterization of a new photolabile protecting group (caging group) for carboxylic acids, the 2-(dimethylamino)-5-nitrophenyl (DANP) group, is described. This compound has a major absorption band in the visible wavelength region with a maximum near 400 nm (epsilon400 = 9077 M(-1) cm(-1) at pH 7.4 and 21 degrees C). The caging group is attached through an ester linkage to the carboxyl functionality of beta-alanine, which activates the inhibitory glycine receptor in the mammalian central nervous system. Such caged compounds play an important role in transient kinetic investigations of fast cellular processes. Upon photolysis of DANP-caged beta-alanine, the caging group is released within 5 micros. Quantum yields of 0.03 and 0.002 were obtained in the UV region (308 and 360 nm) and the visible region (450 nm), respectively. Laser-pulse photolysis experiments, using 337 or 360 nm light, were performed with the caged compound equilibrated with HEK 293 cells transiently transfected with cDNA encoding the alpha1 homomeric, wild-type glycine receptor. The experiments demonstrated that neither DANP-caged beta-alanine nor its byproducts inhibit or activate the glycine receptors on the cell surface. Under physiological conditions, the DANP-caged beta-alanine is water-soluble and stable and can be used for transient kinetic measurements.