Salicyl Alcohol Research Articles

To be or not to be convergent in salicin-based defence in chrysomeline leaf beetle larvae: evidence from Phratora vitellinae salicyl alcohol oxidase

Glandular chemical defence relying on the action of salicylaldehyde is characteristic for Chrysomela leaf beetle larvae. The salicylaldehyde precursor salicin, sequestered from salicaceous host plants, is deglucosylated and the aglycon further oxidized by a salicyl alcohol oxidase (SAO) to the respective aldehyde. SAOs, key enzymes in salicin-based glandular chemical defence, were previously identified and shown to be of a single evolutionary origin in Chrysomela species. We here identified and characterized SAO of Phratora vitellinae, the only species outside the genus Chrysomela that produce salicylaldehyde as a defensive compound. Although Chrysomela and Phratora are not closest relatives, their SAOs share glucose-methanol-choline oxidoreductase (GMC) affiliation, a specific GMCi subfamily ancestor, glandular tissue-specific expression and almost identical gene architectures. Together, this strongly supports a single origin of SAOs of both Chrysomela and Phratora. Closely related species of Chrysomela and P. vitellinae use iridoids as defensive compounds, which are like salicylaldehyde synthesized by the consecutive action of glucosidase and oxidase. However, we elucidated SAO-like sequences but no SAO proteins in the glandular secretion of iridoid producers. These findings support a different evolutionary history of SAO, related genes and other oxidases involved in chemical defence in the glandular system of salicylaldehyde and iridoid-producing leaf beetle larvae.

Host plant shifts affect a major defense enzyme inChrysomela lapponica

Chrysomelid leaf beetles use chemical defenses to overcome predatory attack and microbial infestation. Larvae of Chrysomela lapponica that feed on willow sequester plant-derived salicin and other leaf alcohol glucosides, which are modified in their defensive glands to bioactive compounds. Salicin is converted into salicylaldehyde by a consecutive action of a β-glucosidase and salicyl alcohol oxidase (SAO). The other leaf alcohol glucosides are not oxidized, but are deglucosylated and esterified with isobutyric- and 2-methylbutyric acid. Like some other closely related Chrysomela species, certain populations of C. lapponica shift host plants from willow to salicin-free birch. The only striking difference between willow feeders and birch feeders in terms of chemical defense is the lack of salicylaldehyde formation. To clarify the impact of host plant shifts on SAO activity, we identified and compared this enzyme by cloning, expression, and functional testing in a willow-feeding and birch-feeding population of C. lapponica. Although the birch feeders still demonstrated defensive gland-specific expression, their SAO mRNA levels were 1,000-fold lower, and the SAO enzyme was nonfunctional. Obviously, the loss of catalytic function of the SAO of birch-adapted larvae is fixed at the transcriptional, translational, and enzyme levels, thus avoiding costly expression of a highly abundant protein that is not required in the birch feeders.

Development of a Photolabile Carbonyl-Protecting Group Toolbox

New salicyl alcohol derived photolabile carbonyl protecting groups have been developed, and the effect of substituents on the photochemical properties of photolabile protecting groups (PPGs) has been studied. The 3-(dimethylamino)phenyl groups at the α position prove to be important to the efficiency of the deprotection reactions, as shown in the photo reactions of the acetal 9. On the other hand, expansion of the salicyl alcohol's benzene skeleton to naphthalene does not improve the photochemical properties of PPGs. A neutral protecting protocol has been generalized to new PPGs with α,α-diaryl salicyl alcohol backbone. Thus, installation of PPGs onto aldehydes is readily achieved at 140 °C without using any other chemical reagents. These PPGs are stable under acidic conditions typical for hydrolyzing acetals and constitute orthogonal protecting groups with traditional 1,3-dioxane/1,3-dioxolane for carbonyl compounds. Highly efficient release of carbohydrate molecules is demonstrated, which can be potentially useful in site-specific release and immobilization of carbohydrates for preparation of high-density microarrays. With the enriched PPG toolbox, PPGs are divided into three subgroups based on their UV absorption profiles. PPGs from different subgroups can be sequentially removed by using different UV irradiation wavelengths. For PPGs absorbing UVA (λ >315 nm), photochemical deprotection can be carried out with sunlight in high yields.

Oxidovanadium(V) Complexes with Aminoethanol Bis(phenolate) [O,N,O,O′] Ligands: Preparations, Structures, N‐Dealkylation and Condensation Reactions

AbstractThe reactions between [VO(acac)2] (acac– = acetylacetonate ion) or [VO(OPr)3] and trianionic tetradentate N,N‐bis(2‐methylene‐4,6‐alkylphenolate)aminoethanolate ligands, [L13– (4,6‐dimethyl), L23– (4‐methyl, 6‐tert‐butyl), L33– (4‐tert‐butyl, 6‐methyl), L43– (4,6‐di‐tert‐butyl)], afford mononuclear complexes [VO(L1)] (1) and [VO(L2)] (2) with a trigonal bipyramidal coordination sphere around the VV ion, or dinuclear octahedral complexes [V2O2(L3)2] (3) and [V2O2(L4)2] (4). In methanol an adduct with the formula [VO(L1)(MeOH)]·1/2MeOH (5) is obtained. According to multinuclear NMR spectroscopy all those complexes have a mononuclear structure in CDCl3 solutions. In wet polar solvents complex 1 reacts with water and N‐dealkylation occurs producing 3,5‐dimethylsalicyl alcohol, which condensates with 1 and forms a new oxidovanadium complex 6. An ether bond links 3,5‐dimethylsalicyl alcohol to the L13– ligand. To support the reaction mechanism, we have found that in dry acetonitrile 1 reacts directly with salicyl alcohol forming compound 7, which is similar to 6. All compounds 1–7 have been characterized by elemental analysis, multinuclear NMR and X‐ray diffraction.

Effect of Organic Cations and Solvents on the Ion-Pair Extraction of Boric Acid with Salicyl Alcohol

Effect of Organic Cations and Solvents on the Ion-Pair Extraction of Boric Acid with Salicyl Alcohol

Predicting the substrate specificity of a glycosyltransferase implicated in the production of phenolic volatiles in tomato fruit

The volatile compounds that constitute the fruit aroma of ripe tomato (Solanum lycopersicum) are often sequestered in glycosylated form. A homology-based screen was used to identify the gene SlUGT5, which is a member of UDP-glycosyltransferase 72 family and shows specificity towards a range of substrates, including flavonoid, flavanols, hydroquinone, xenobiotics and chlorinated pollutants. SlUGT5 was shown to be expressed primarily in ripening fruit and flowers, and mapped to chromosome I in a region containing a QTL that affected the content of guaiacol and eugenol in tomato crosses. Recombinant SlUGT5 protein demonstrated significant activity towards guaiacol and eugenol, as well as benzyl alcohol and methyl salicylate; however, the highest in vitro activity and affinity was shown for hydroquinone and salicyl alcohol. NMR analysis identified isosalicin as the only product of salicyl alcohol glycosylation. Protein modelling and substrate docking analysis were used to assess the basis for the substrate specificity of SlUGT5. The analysis correctly predicted the interactions with SlUGT5 substrates, and also indicated that increased hydrogen bonding, due to the presence of a second hydrophilic group in methyl salicylate, guaiacol and hydroquinone, appeared to more favourably anchor these acceptors within the glycosylation site, leading to increased stability, higher activities and higher substrate affinities.

ChemInform Abstract: Synthesis of 1,2,4‐Triazolo[5,1‐b][1,3]benzoxazines.

Alkylation of 1H-azoles by salicyl alcohol to give 2-(1H-azolylmethyl)phenols has been studied in some detail [1-3]. In the presence of good leaving groups in the azole molecules a subsequent cyclization of the initially formed alkylation products can occur to give azolo[1,3]benzoxazines [4]. We propose a simple, one-stage method for the preparation of the 1,2,4-triazolo[5,1-b][1,3]benzoxazines 2a,b through the reaction of 3-chloro-1,2,4-triazole (1a) or 3,5-dibromo-1,2,4-triazole (1b) with salicyl alcohol in refluxing DMF in the presence of K2CO3. The reaction occurs through the stage of intermediate formation of o-methylenequinone generated in situ from salicyl alcohol. IR spectra were recorded on a Shimadzu FTIR-8400S spectrophotometer for KBr tablets. The H NMR spectra were taken on a Bruker AM-400 (400 MHz) spectrometer using DMSO-d6 and with TMS as internal standard. Mass spectra were recorded on a Finnigan Trace DSQ chromato-mass spectrometer with direct introduction of the sample into the ion source.

Synthesis of 1,2,4-triazolo[5,1-b][1,3]benzoxazines

Alkylation of 1H-azoles by salicyl alcohol to give 2-(1H-azolylmethyl)phenols has been studied in some detail [1-3]. In the presence of good leaving groups in the azole molecules a subsequent cyclization of the initially formed alkylation products can occur to give azolo[1,3]benzoxazines [4]. We propose a simple, one-stage method for the preparation of the 1,2,4-triazolo[5,1-b][1,3]benzoxazines 2a,b through the reaction of 3-chloro-1,2,4-triazole (1a) or 3,5-dibromo-1,2,4-triazole (1b) with salicyl alcohol in refluxing DMF in the presence of K2CO3. The reaction occurs through the stage of intermediate formation of o-methylenequinone generated in situ from salicyl alcohol. IR spectra were recorded on a Shimadzu FTIR-8400S spectrophotometer for KBr tablets. The H NMR spectra were taken on a Bruker AM-400 (400 MHz) spectrometer using DMSO-d6 and with TMS as internal standard. Mass spectra were recorded on a Finnigan Trace DSQ chromato-mass spectrometer with direct introduction of the sample into the ion source.

Medicinal potential of willow: A chemical perspective of aspirin discovery

The willow tree is a symbolic medicinal plant that has been associated with the discovery of aspirin, chemically known as acetylsalicylic acid, or salicylate, which still offers surprises as a revival drug. The philosophical perspective of the significance of the willow tree has been elaborated since the Assyrians (4000 BC) and Sumerians (3500 BC), who were aware of its medicinal merits. In 1838, the main pharmacologically active ingredient of willow, the salicin structure was elucidated by hydrolysis to comprise D-glucose and salicyl alcohol. These uncovered new perspectives, which eventually lead to the discovery of aspirin.

One pot synthesis of a soluble polymer for zirconium carbide

A new polymer, polyzirconoxanesal (PZS), is synthesized from the reaction of zirconium oxychloride octahydrate (ZrOCl 2·8H 2O) with acetylacetone (Hacac) and salicyl alcohol (SA) by one-pot protocol. The polymer is soluble in common organic solvents, such as ethanol, methanol, acetone, tetrahydrofuran and chloroform, and exhibits rheology with viscosity of 100–300 mpa s at 25 °C. These properties are suitable for uses in fabrication of ceramic matrix fiber composites. Pyrolysis of this polymer at 1300 °C in argon provides nanosized ZrC with spherical morphology and size of 20–100 nm.

Biosynthesis of Phenolic Glycosides from Phenylpropanoid and Benzenoid Precursors in Populus

Salicylate-containing phenolic glycosides (PGs) are abundant and often play a dominant role in plant-herbivore interactions of Populus and Salix species (family Salicaceae), but the biosynthetic pathway to PGs remains unclear. Cinnamic acid (CA) is thought to be a precursor of the salicyl moiety of PGs. However, the origin of the 6-hydroxy-2-cyclohexen-on-oyl (HCH) moiety found in certain PGs, such as salicortin, is not known. HCH is of interest because it confers toxicity and antifeedant properties against herbivores. We incubated Populus nigra leaf tissue with stable isotope-labeled CA, benzoates, and salicylates, and measured isotopic incorporation levels into both salicin, the simplest PG, and salicortin. Labeling of salicortin from [13C6]-CA provided the first evidence that HCH, like the salicyl moiety, is a phenylpropanoid derivative. Benzoic acid and benzaldehyde also labeled both salicyl and HCH, while benzyl alcohol labeled only the salicyl moiety in salicortin. Co-administration of unlabeled benzoates with [13C6]-CA confirmed their contribution to the biosynthesis of the salicyl but not the HCH moiety of salicortin. These data suggest that benzoate interconversions may modulate partitioning of phenylpropanoids to salicyl and HCH moieties, and hence toxicity of PGs. Surprisingly, labeled salicyl alcohol and salicylaldehyde were readily converted to salicin, but did not result in labeled salicortin. Co-administration of unlabeled salicylates with labeled CA suggested that salicyl alcohol and salicylaldehyde may have inhibited salicortin biosynthesis. A revised metabolic grid model of PG biosynthesis in Populus is proposed, providing a guide for functional genomic analysis of the PG biosynthetic pathway.

Catalytic methylation of phenol on MgO – Surface chemistry and mechanism

Reactions of phenol and methanol catalyzed by MgO have been explored by kinetic measurements and in situ IR spectroscopy combined with computational studies of sorbed molecules. On MgO, methanol partly transforms to formaldehyde above 250 °C. Adsorbed phenol forms phenolate species, and the energetically preferred mode of adsorption leads to an almost orthogonal orientation of the aromatic ring with respect to the catalyst surface. All molecules involved adsorb preferably at the corner sites of MgO (three-co-ordinated Mg atoms). The main reaction products are anisole and o-cresol, the latter dominating above 300 °C. At very low conversions, salicylic aldehyde is observed as primary reaction product, being rapidly transformed to o-cresol. It is only observed during the initial accumulation of adsorbed species on the catalyst surface, but not under steady-state conditions on a fully covered catalyst surface. Therefore, o-cresol formation starts with the reaction between phenol and formaldehyde to salicylic alcohol, which in turn is rapidly transformed to salicylic aldehyde and subsequently to o-cresol. Salicylic aldehyde may also form via the bimolecular disproportionation of salicylic alcohol to o-cresol and aldehyde. The parallel reaction to o-cresol, not involving the formation of salicylic aldehyde as intermediate, proceeds via the reduction of salicylic alcohol to o-cresol by formaldehyde. The identified mechanism may open new synthetic approaches for the production of functionalized phenol derivatives and, even more importantly, for the defunctionalization of substituted phenols potentially available at large scale from deconstructed lignin.

Glycosylation-mediated phenylpropanoid partitioning in Populus tremuloides cell cultures

BackgroundPhenylpropanoid-derived phenolic glycosides (PGs) and condensed tannins (CTs) comprise large, multi-purpose non-structural carbon sinks in Populus. A negative correlation between PG and CT concentrations has been observed in several studies. However, the molecular mechanism underlying the relationship is not known.ResultsPopulus cell cultures produce CTs but not PGs under normal conditions. Feeding salicyl alcohol resulted in accumulation of salicins, the simplest PG, in the cells, but not higher-order PGs. Salicin accrual reflected the stimulation of a glycosylation response which altered a number of metabolic activities. We utilized this suspension cell feeding system as a model for analyzing the possible role of glycosylation in regulating the metabolic competition between PG formation, CT synthesis and growth. Cells accumulated salicins in a dose-dependent manner following salicyl alcohol feeding. Higher feeding levels led to a decrease in cellular CT concentrations (at 5 or 10 mM), and a negative effect on cell growth (at 10 mM). The competition between salicin and CT formation was reciprocal, and depended on the metabolic status of the cells. We analyzed gene expression changes between controls and cells fed with 5 mM salicyl alcohol for 48 hr, a time point when salicin accumulation was near maximum and CT synthesis was reduced, with no effect on growth. Several stress-responsive genes were up-regulated, suggestive of a general stress response in the fed cells. Salicyl alcohol feeding also induced expression of genes associated with sucrose catabolism, glycolysis and the Krebs cycle. Transcript levels of phenylalanine ammonia lyase and most of the flavonoid pathway genes were reduced, consistent with down-regulated CT synthesis.ConclusionsExogenous salicyl alcohol was readily glycosylated in Populus cell cultures, a process that altered sugar utilization and phenolic partitioning in the cells. Using this system, we identified candidate genes for glycosyltransferases that may mediate the glycosylation, and for transporters that mediate the subcellular compartmentalization of sugars and phenolic glycosides. The suspension cells appear to represent a facile system for dissecting the regulation of phenolic carbon partitioning, and in turn, its effects on growth in Populus.

A New Flavonoid Glycoside from Salix denticulata Aerial Parts

Abstract: A new flavonoid glycoside (1) has been isolated from the aerial parts of Salix denticulata (Salicaceae) together with five known compounds, β-sitosterol, 2,6-dihydroxy- 4-methoxy acetophenone, eugenol-1-O-β-D-glucopyranoside, 1-O-β-D-(3’-benzoyl) salicyl alcohol and luteolin-7-O-β-D-glucopyranosyl-(1-6)-glucopyranoside. The structure of 1 was elucidated as 2’,5-dihydroxy-3’-methoxyflavone-7-O-β-D-glucopyranoside by means of chemical and spectral data including 2D NMR studies.

Antiproliferative activity: Extract versus isolated active constituent

Recently, there have been extensive efforts to evaluate the chemopreventive role of substances present in natural products. We compared the antiproliferative potency (measured by WST-1 assay) of four plant extracts from the gum resin of Boswellia serrata Roxb., Hypericum perforatum L., Cimicifuga racemosa L.and Salix sp. to their biologically active compounds boswellic acid (AKBA), hypericin (HY), hyperforin (HP), triterpene glycosides (TTG), cinnamic acid esters (CAE) and salicin (SAL) using different cancer cells. Substances were compared by their GI50 values. In three leukaemia cell lines (K562, U937 and MOLT-4) the effect of the crude extract of B. serrata was 2.3–3.3 times more potent than AKBA [1].The antiproliferative effect of H. perforatum extract depends on light activation of HY. However, in the dark, the effect of H. perforatum extract on K562 and U937 cells was found 10-times more potent than HY, but 2-times less potent than HP [2]. Furthermore, HY and HP acted synergistically on cell growth inhibition in the dark [3]. The effect of two main classes of compounds, TTG and CAE on breast ER+ MCF-7 and ER- MDA MB231 cancer cells was 2.2–3 times and 4–6 times less potent in comparison to their parent isopropanolic C. racemosa extract [4]. Effect of willow bark extract, its fraction of salicylic alcohol derivates F1 [5] and SAL was investigated on the cell growth of COX-2-proficient HT-29 and COX-2-deficient HCT 116 colon cancer cells. There were differences of about two decades of logarithmic scale for favour of extract in comparison to the single compound SAL and the parent extract was 3-times more potent than the isolated fraction F1. Natural products as a multiple compounds mixtures possess the potential to attack cancer cells more effectively than their single active constituents.

Interaction of boric acid with salicyl derivatives as an anchor group of boron-selective adsorbents

The complexation of boric acid with salicylic acid, salicyl alcohol and bis(hydroxymethyl)phenol derivatives has been investigated in detail using 11B NMR spectroscopy. Boric acid accepts an electron pair through the nucleophilic attack of the ligand, followed by a condensation reaction, to form the 1:1 monochelate complex. The monochelate complex then reacts with the ligand through the condensation reaction to give the 1:2 bischelate complex. Bis(hydroxymethyl)phenol derivatives formed quite stable chelate complexes among the examined salicyl derivatives. It was clarified by molecular modeling calculations that the complexation with bis(hydroxymethyl)phenol derivatives was highly favorable from an enthalpy viewpoint. An anion-exchange resin presorbed with 3,5-bis(hydroxymethyl)-4-hydroxybenzoate had a strong adsorbability of boron over a wide pH range. The adsorbent quantitatively removed boron up to approximately a half amount of the loaded ligand, which indicated that the boron species adsorbed onto the resin was predominantly present as the −3 charged 1:2 bischelate complex. The formation constant of the 1:2 bischelate complex with 3,5-bis(hydroxymethyl)-4-hydroxybenzoate in the resin phase was estimated to be log β ¯ f ( BLAc2 ) = 5.0 , which almost agreed with those of the salicyl alcohol derivatives in aqueous solutions.

Salicyl Alcohol Oxidase of the Chemical Defense Secretion of Two Chrysomelid Leaf Beetles: MOLECULAR AND FUNCTIONAL CHARACTERIZATION OF TWO NEW MEMBERS OF THE GLUCOSE-METHANOL-CHOLINE OXIDOREDUCTASE GENE FAMILY

Salicyl alcohol oxidase is an extracellular enzyme that occurs in glandular reservoirs of chrysomelid leaf beetle larvae and catalyzes the formation of salicylaldehyde, a volatile deterrent used by the larvae against predators. Salicyl alcohol is the hydrolysis product of salicin, a plant-derived precursor taken up by the beetle larvae from the leaves of willow and poplar trees. The cDNA encoding salicyl alcohol oxidase from two related species Chrysomela tremulae and Chrysomela populi has been identified, cloned, and expressed in an active form in Escherichia coli. The open reading frame of 623 amino acids begins in both enzymes with an N-terminal signal peptide of 21 amino acids. Sequence comparison has revealed that salicyl alcohol oxidase belongs to the family of glucose-methanol-choline oxidoreductase-like sequences with mostly unknown function. Enzymes of this family share similar overall structure with an essentially identical FAD-binding site but possess different catalytic activities. The data suggest that salicyl alcohol oxidase, essential for the activation of the plant-derived precursor salicin, was originally recruited from an oxidase involved in the autogenous biosynthesis of iridoid monoterpenes and found in related chrysomelid leaf beetle species.

Acetylene-grafted resins derived from phenolics via azo coupling reaction

Novel phenolic resins with high ethynyl contents were realized via azo coupling reaction between phenol units and diazonium of 3-ethynylaniline. If Novolac and high-ortho Novolac resins were used as the starting materials directly, the ratio of ethynyl groups to phenolic rings was ca 70%; while the ratio was 100% for the resin from Friedel–Craft polycondensation of 4-(3-ethynylphenyl)salicyl alcohol. All the resins were readily soluble in acetone and ethanol, and meltable at temperatures below 100°C. The resins underwent thermal addition-type cure with a broad exotherm of around 140–280°C, and the starting curing temperature showed a downward drift with increase in the ethynyl content. The thermal properties of the cured resins, determined from thermogravimetric analysis (TGA), were considerably superior to those of Novolac- and Resole-type phenolic resins. The initial decomposition temperatures were at ca 400°C, and the anaerobic carbon yields were ca 80% for all the resins.

In vitro inhibition of soredial growth in the epiphytic lichen Physcia tenella (Ascomycetes: Lecanorales) by a variety of bark phenols

Abstract:The in-vitro growth rate of soredia from the epiphytic lichen species Physcia tenella was tested at different concentrations of phenols added in an in vitro experiment designed to evaluate the allelopathic effects of bark derived substances in stem flow. The conditions used were designed to resemble those found on bark of Populus×canadensis, as this tree species has been widely used for lichen mapping studies in Germany. Bark phenolic glycosides, flavonoids and tannins undergo hydrolytic decomposition in stem flow, resulting in a variety of monomeric phenolic acids, aldehydes and alcohols. Eleven phenolic substances of different biosynthetic origin in the concentration range between 10−6 M and 10−3 M in the culture medium were tested. IC50 values were calculated for each substance. Inhibition was highest for catechol, substituted phenolic glycosides, benzoic and ellagic acids, moderate for flavonoids, gallic acid, salicylic alcohol, salicylic aldehyde and low for salicylic acid. The tests show that bark phenols in natural concentrations inhibit soredial growth of the test species Physcia tenella and therefore have an influence on the growth of lichens on trees.

Enzymatic Synthesis of α-Anomer-SelectiveD-Glucosides Using Maltose Phosphorylase

A maltose phosphorylase (EC 2.4.1.8; MPase) showed novel acceptor specificity and transferred the glucosyl moiety of maltose not only to sugars but also to various acceptors having alcoholic OH groups. Salicyl alcohol acted as acceptor for MPase from Enterococcus hirae, and the product, salicyl-O-alpha-D-glucopyranoside (alpha-SalGlc) was identified. The yield based on supplied salicyl alcohol was 86% (mol/mol).