Triply Adaptive Libraries of Dynamic Covalent Macrocycles: Switching between Sorted and Unsorted States.

Dynamic noncovalent and covalent chemistries have enabled the constitutional modulation of chemical entities within chemical dynamic systems. The switching between order and disorder, i.e., self-sorted and unsorted states of constitutional dynamic libraries, remains challenging. Herein, we study the adaptive behaviors of a dynamic library of imine macrocycles generated from dialdehydes and diamines, seeking ways to exert control over sorting and unsorting processes. The distribution of constituents in the present library of dynamic macrocycles is modulated in response to internal and external effectors (e.g., time, metal cations, and chemical fuels), resulting in the transient amplification of self-sorted constituents in out-of-equilibrium states. The present study showcases higher complexity in systems subject to multiple adaptation through the dynamic interconversion between singularity/order and diversity/disorder.

Selective Transition Enhancement in a g-Engineered Diradical.

A diradical with engineered g-asymmetry was synthesized by grafting a nitroxide radical onto the [Y(Pc)2]⋅ radical platform. Various spectroscopic techniques and computational studies revealed that the electronic structures of the two spin systems remained minimally affected within the diradical system. Fluid-solution Electron Paramagnetic Resonance (EPR) experiments revealed a weak exchange coupling with |J| ~ 0.014 cm-1, subsequently rationalized by CAS-SCF calculations. Frozen solution continuous-wave (CW) EPR experiments showed a complicated and power-dependent spectrum that eluded analysis using the point-dipole model. Pulse EPR manipulations with varying microwave powers, or under varying magnetic fields, demonstrated that different resonances could be selectively enhanced or suppressed, based on their different tipping angles. In particular, Field-Swept Echo-Detected (FSED) spectra revealed absorptions of MW power-dependent intensities, while Field-Swept Spin Nutation (FSSN) experiments revealed two distinct Rabi frequencies. This study introduces a methodology to synthesize and characterize g-asymmetric two-spin systems, of interest in the implementation of spin-based CNOT gates.

Isoselective Hydroformylation of Propylene by Iodide-Assisted Palladium Catalysis.

Isobutanal is a high value bulk material that, in principle, could be produced with 100 % atom-economy by isoselective hydroformylation of propylene with syngas. However, leading industrial Rh- and Co-catalyzed hydroformylation methods preferentially form n-butanal over the iso-product, and methods offering isoselectivity remain underdeveloped. Here we report an iodide-assisted Pd-catalyzed hydroformylation of propylene that produces isobutanal with unprecedented levels of selectivity. The method involves PdI2 , simple alkyl monophosphines, such as tricyclohexylphosphine, and common green solvents, enabling the title reaction to occur with isoselectivity in up to 50 : 1 iso/n product ratios under industrially relevant conditions (80-120 °C). The catalytic and preliminary mechanistic experiments indicate a key role of the iodide anions in both the catalytic activity and the isoselectivity.

Impact of Light Intensity on Antioxidant Activity of Tropical Microalgae.

Twelve microalgae species isolated in tropical lagoons of New Caledonia were screened as a new source of antioxidants. Microalgae were cultivated at two light intensities to investigate their influence on antioxidant capacity. To assess antioxidant property of microalgae extracts, four assays with different modes of action were used: 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-éthylbenzothiazoline-6-sulphonique) (ABTS), oxygen radical absorbance capacity (ORAC), and thiobabituric acid reactive substances (TBARS). This screening was coupled to pigment analysis to link antioxidant activity and carotenoid content. The results showed that none of the microalgae studied can scavenge DPPH and ABTS radicals, but Chaetoceros sp., Nephroselmis sp., and Nitzschia A sp. have the capacity to scavenge peroxyl radical (ORAC) and Tetraselmis sp., Nitzschia A sp., and Nephroselmis sp. can inhibit lipid peroxidation (TBARS). Carotenoid composition is typical of the studied microalgae and highlight the siphonaxanthin, detected in Nephroselmis sp., as a pigment of interest. It was found that xanthophylls were the major contributors to the peroxyl radical scavenging capacity measured with ORAC assay, but there was no link between carotenoids and inhibition of lipid peroxidation measured with TBARS assay. In addition, the results showed that light intensity has a strong influence on antioxidant capacity of microalgae: Overall, antioxidant activities measured with ORAC assay are better in high light intensity whereas antioxidant activities measured with TBARS assay are better in low light intensity. It suggests that different antioxidant compounds production is related to light intensity.

Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives.

22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2',3,4',6'-tetramethoxychalcone (FKd 19). FKd induced a G1/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24h-effect on Akt/mTor normal cells versus a 48h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents.

Two New Stilbenoids from the Aerial Parts of Arundina graminifolia (Orchidaceae).

Two new phenanthrene derivatives, a phenanthrenequinone named arundiquinone (1) and a 9,10-dihydrophenanthrene named arundigramin (2) together with a known lignin dimer (3) and seven known stilbenoids (4-10) were isolated from the aerial parts of the Asian orchid Arundina graminifolia. The structures of the isolated compounds were elucidated by spectroscopic methods, including extensive 1D, 2D NMR (heteronuclear single quantum coherence (HSQC), heteronuclear multiple-bond correlation spectroscopy (HMBC), and HR-ESI-MS techniques, as well as comparison with respective literature reports. The cytoprotective activity of the isolated compounds were evaluated for their ability to reduce beta amyloid induced toxicity on undifferentiated PC12 cells. Compound 8 showed moderate cytoprotective activity at 0.5 µmol/L (71% of cell viability) while the other compounds showed no significant activity at the highest concentration tested.

Chemical Constituents from the Aerial Parts of Cyrtopodium paniculatum.

We report the first phytochemical study of the neotropical orchid Cyrtopodium paniculatum. Eight new compounds, including one phenanthrene 1, one 9,10-dihydro-phenanthrene 2, one hydroxybenzylphenanthrene 3, two biphenanthrenes 4-5, and three 9,10 dihydrophenanthrofurans 6-8, together with 28 known phenolic compounds, mostly stilbenoids, were isolated from the CH2Cl2 extract of its leaves and pseudobulbs. The structures of the new compounds were established on the basis of extensive spectroscopic methods.

Identification of phenanthrene derivatives in Aerides rosea (Orchidaceae) using the combined systems HPLC-ESI-HRMS/MS and HPLC-DAD-MS-SPE-UV-NMR.

INTRODUCTION: In our continued efforts to contribute to the general knowledge on the chemical diversity of orchids, we have decided to focus our investigations on the Aeridinae subtribe. Following our previous phytochemical study of Vanda coerulea, which has led to the identification of phenanthrene derivatives, a closely related species, Aerides rosea Lodd. ex Lindl. & Paxton, was chosen for investigation. OBJECTIVE: To identify new secondary metabolites, and to avoid isolation of those already known, by means of the combined systems HPLC-DAD(diode-array detector) with high-resolution tandem mass spectrometry (HRMS/MS) and HPLC-DAD-MS-SPE(solid-phase extraction)-UV-NMR. METHODS: A dereplication strategy was developed using a HPLC-DAD-HRMS/MS targeted method and applied to fractions from A. rosea stem extract. Characterisation of unknown minor compounds was then performed using the combined HPLC-DAD-MS-SPE-UV-NMR system. RESULTS: The dereplication method allowed the characterisation of four compounds (gigantol, imbricatin, methoxycoelonin and coelonin), previously isolated from Vanda coerulea stem extract. The analyses of two fractions permitted the identification of five additional minor constituents including one phenanthropyran, two phenanthrene and two dihydrophenanthrene derivatives. The full set of NMR data of each compound was obtained from microgram quantities. CONCLUSION: Nine secondary metabolites were characterised in A. rosea stems, utilising HPLC systems combined with high-resolution analytical systems. Two of them are newly described phenanthrene derivatives: aerosanthrene (5-methoxyphenanthrene-2,3,7-triol) and aerosin (3-methoxy-9,10-dihydro-2,5,7-phenanthrenetriol).

Atropisomerism about aryl-Csp(3) bonds: the electronic and steric influence of ortho-substituents on conformational exchange in cannabidiol and linderatin derivatives.

Terpenylation reactions of substituted phenols were used to prepare cannabidiol and linderatin derivatives, and their structure and conformational behavior in solution were investigated by NMR and, for some representative examples, by DFT. VT-NMR spectra and DFT calculations were used to determine the activation energies of the conformational change arising from restricted rotation about the aryl-Csp(3) bond that lead to two unequally populated rotameric epimers. The NBO calculation was applied to explain the electronic stabilization of one conformer over another by donor-acceptor charge transfer interactions. Conformational control arises from a combination of stereoelectronic and steric effects between substituents in close contact with each other on the two rings of the endocyclic epoxide atropisomers. This study represents the first exploration of the stereoelectronic origins of atropisomerism around C(sp(2))-C(sp(3)) single bonds through theoretical calculations.

Nucleophilic substitution of azide acting as a pseudo leaving group: one-step synthesis of various aza heterocycles.

The reaction of 3-azidopropanoic acid with the carbodiimide-based coupling reagent DIC leads to a six-membered-ring intermediate acting as a versatile precursor to a diverse set of aza heterocycles, including mono-, bi-, and tricyclic compounds.

Dynamic covalent self-assembly and self-sorting processes in the formation of imine-based macrocycles and macrobicyclic cages.

Investigating the self-assembly and self-sorting behaviour of dynamic covalent organic architectures makes possible the parallel generation of multiple discrete products in a single one pot procedure. We here report the self-assembly of covalent organic macrocycles and macrobicyclic cages from dialdehyde and polyamine components via multiple [2 + 2] and [3 + 2] polyimine condensations. Furthermore, component self-sorting processes have been monitored within the dynamic covalent libraries formed by these macrocycles and macrobicyclic cages. The progressive assembly of the final structures involves intermediates which undergo component selection and self-correction to generate the final thermodynamic constituents. The homo-self-sorting observed seems to involve entropic factors, as the homoleptic species present a higher symmetry than the competing heteroleptic ones. This study not only emphasizes the importance of an adequate design of the components of complex self-sorting systems, but also verifies the conjecture that systems of higher complexity may generate simpler outputs through the operation of competitive self-sorting.

Direct guanidinylation of aryl and heteroaryl halides via copper-catalyzed cross-coupling reaction.

A modified Ullmann reaction using p-methoxybenzyl (PMB) guanidine as guanidinylation agent yielded various aryl and heteroaryl guanidines in good yields.

In vitro antileishmanial, antiplasmodial and cytotoxic activities of a new ventiloquinone and five known triterpenes from Parinari excelsa.

CONTEXT: Parinari excelsa Sabine (Chrysobalanaceae) is an indigenous tree from West and Eastern Africa. This tree is used in Ivory Coast as an antimalaria remedy. OBJECTIVE: The in vitro antiplasmodial and antileishmanial activities of the stem bark, the leaf and the major compounds from the stem bark were investigated. MATERIALS AND METHODS: The leaves and stem bark from P. excelsa were separately collected, air-dried and powdered. Two extracts (methylene chloride and methanol) were realized for both powders. Every extract was tested for its antiplasmodial and antileishmanial activities. Only the stem bark crude extracts were fractionated by column chromatography and their major components were analyzed by NMR, HRESIMS and IR methods. The compounds were tested for their antiplasmodial and antileishmanial activities. RESULTS: The comparison of the IC(50) values of the crude extracts were in this order: 3.41 (IC(50) of PeBMc) <4.10 (IC(50) of PeBMc) <4.42 (IC(50) of PeLMe) against P. falciparum and 5.19 (IC(50) of PeBMc) <12.32 (IC(50) of PeBMe) <19.33 (IC(50) of PeLMc) <32.37 (IC(50) of PeLMe) against L. donovani. The stem bark crude extracts were the most active against both parasites. Their fractionation leaded to a new ventiloquinone, five triterpenes and one chlorogenic acid. All these compounds were isolated for the first time from P. excelsa. High activities were observed with (3ß)-3-hydroxyolean-12-en-28-oic acid (IC(50) = 8.2 µM) and 3ß-hydroxyolean-5,12-dien-28-oic acid (IC(50) = 7.7 µM) against L. donovani. With the antiplasmodial activity, the best activity was observed with 16ß-hydroxylupane-1,20(29)-dien-3-one (IC(50) = 28.3 µM). DISCUSSION AND CONCLUSION: These findings demonstrated that the constituents of P. excelsa stem bark have in vitro antiplasmodial and antileishmanial activities.

Novel thiophene-based donor-acceptor scaffolds as cathodes for rechargeable aqueous zinc-ion hybrid supercapacitors.

Well-defined π-conjugated thiophene donor-acceptor molecules play an important role in different fields ranging from synthetic chemistry to materials science. Their chemical structure provides specific electronic and physicochemical properties, which can be further tuned by the introduction of functional groups. Herein, we design and synthesize two novel thiophene-based π-conjugated donor-acceptor molecules TDA-1 and TDA-2 through Aldol and Knoevenagel condensations. In our proof-of-concept study we report for the first time on the use of small organic molecules employed in aqueous zinc-ion hybrid supercapacitors (Zn-HSCs),which exhibit capacitance as high as 206.7 and 235.2 F g-1 for TDA-1, and TDA-2, respectively.

Anti-inflammatory activities of Coleus forsteri (formerly Plectranthus forsteri) extracts on human macrophages and chemical characterization.

Introduction: Formerly named Plectranthus forsteri, Coleus forsteri (Benth.) A.J.Paton, 2019 is a Lamiaceae traditionally used to treat flu-like symptoms and shock-related ecchymosis, especially in the Pacific region. Few studies investigated chemical composition and anti-inflammatory potential of this plant. Method: Herein, we investigated anti-inflammatory potential of C. forsteri ethanolic (ePE) and cyclohexane (cPE) plant extract on LPS-induced human macrophages models and quantified cytokines and quinolinic acid (QUIN) as inflammatory markers. Results: Our results show that extract of ePE and cPE significantly inhibit inflammatory cytokine IL-6 and TNF-α induced by LPS on PMA-derived THP-1 macrophages. QUIN production is also diminished under ePE and cPE treatment in activated human monocyte-derived macrophages (MDMs). Seven abietane diterpenes were characterized from C. forsteri cPE including coleon U (1), coleon U-quinone (2), 8α,9α-epoxycoleon U-quinone (3), horminone or 7α-hydroxyroyleanone (4), 6ß,7α-dihydroxyroyleanone (5), 7α-acetoxy-6ß-hydroxyroyleanone (6) and 7α-formyloxy-6ß-hydroxyroyleanone (7). Discussion: We discussed potential contributions of these molecules from C. forsteri extracts for their anti-inflammatory activities.

New triterpenoid saponin from the stems of Albizia adianthifolia (Schumach.) W.Wight.

As part of our continuing study of apoptosis-inducing saponins from Cameroonian Albizia genus, one new triterpenoid saponin, named adianthifolioside J (1), together with the known gummiferaoside E (2), were isolated from Albizia adianthifolia stems. The structure of the new saponin (1), was established on the basis of extensive analysis of 1 D and 2 D NMR (1H-, 13C-NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC) and HRESIMS experiments, and by chemical evidence as 3-O-[ß-D-xylopyranosyl-(1→2)-ß-D-fucopyranosyl-(1→6)-ß-D-glucopyranosyl]-21-O-{(2E,6S)-2-(hydroxymethyl)-6-methyl-6-O-{4-O-[(2E,6S)-2,6-dimethyl-6-O-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]-(ß-D-quinovopyranosyl)octa-2,7-dienoyl]}acacic acid-28-O-ß-D-glucopyranosyl-(1→3)-[5-O-acetyl-α-L-arabinofuranosyl-(1→4)]-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl ester (1). The pro-apoptotic activity of the new isolated saponin 1 was evaluated, using Annexin V-FITC binding assay, on the A431 human epidermoid cancer cell. The result showed that adianthifolioside J (1) displayed weak pro-apoptotic activity.

Glucosyloxybenzyl eucomate derivatives from Vanda teres stimulate HaCaT cytochrome c oxidase.

Eucomic acid [(2R)-2-(p-hydroxybenzyl)malic acid)] (1) and three new glucopyranosyloxybenzyl eucomate derivatives, vandaterosides I (2), II (3), and III (4), were isolated and identified from the stems of Vanda teres. Their cellular antiaging properties were evaluated in a human immortalized keratinocyte cell line (HaCaT) by monitoring their effect on cytochrome c oxidase activity, implicated in mitochondrial respiratory function and cellular energy production. Eucomic acid (1) and vandateroside II (3) increased cytochrome c oxidase activity and/or expression, without enhancing cellular mitochondrial content. These two V. teres biomarkers apparently contributed to stimulate respiratory functions in keratinocytes. Since aging and its pathologies may be ascribed to a decline in mitochondrial functions, these biomarkers have the potential to become new natural ingredients for antiaging preparations to remedy age-related disorders such as skin aging.

Glycosides of polygalacic acid from the stem barks of Piper guineense Schum and Thonn.

In a continuation of our study on constituents of P. guineense now focusing on the search for saponins, phytochemical investigation of the n-BuOH fraction of P. guineense stem bark led to the isolation of three previously undescribed triterpenoid saponins, named guineenosides A─C (1─3). Their structures were established on the basis of extensive analysis of 1D and 2D NMR (1H, 13C NMR, DEPT, COSY, TOCSY, NOESY, HSQC, HSQC-TOCSY and HMBC) and HRESIMS experiments, and by chemical evidence as 3-O-{α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-[α-l-arabinofuranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-fucopyranosyl} polygalacic acid 28-O-α-l-rhamnopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl ester (1), 3-O-{α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl-(1 â†’ 2)-α-l-arabinopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-[α-l-arabinofuranosyl-(1 â†’ 4)]-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-fucopyranosyl} polygalacic acid 28-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-rhamnopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl ester (2), and 3-O-{α-l-rhamnopyranosyl-(1 â†’ 2)-ß-d-xylopyranosyl-(1 â†’ 3)-ß-d-fucopyranosyl} polygalacic acid 28-O-[α-l-rhamnopyranosyl-(1 â†’ 4)-α-l-rhamnopyranosyl-(1 â†’ 3)-ß-d-xylopyranosyl ester (3). This is the first report of triterpenoid saponins from P. guineense.

Theoretical mechanistic study of the TBD-catalyzed intramolecular aldol reaction of ketoaldehydes.

The intramolecular aldol reaction of acyclic ketoaldehydes catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is investigated using density functional theory calculations. Compared to the proline-catalyzed aldol reaction, the use of TBD provides a unique and unusual complete switch of product selectivity. Three mechanistic pathways are proposed and evaluated. The calculations provide new insights into the activation mode of bifunctional guanidine catalysts. In the favored mechanism, TBD first catalyzes the enolization of the substrate and then the C-C bond formation through two concerted proton transfers. In addition, the computationally predicted stereochemical outcome of the reaction is in agreement with the experimental findings.

Novel chiral derivatizing isothiocyanate-based agent for the enantiomeric excess determination of amines.

The expedient synthesis of a novel chiral (1S,2S)-N-[(2-isothiocyanato)cyclohexyl] trifluoromethanesulfonamide and its use as a derivatizing auxiliary for the straightforward determination of optical purity of chiral amines are reported.