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The present study was designed to evaluate the immunomodulatory effects of the secoiridoid from extra virgin olive oil, oleacein (OLA), deepening into the possible signaling pathways involved in LPS-activated murine peritoneal macrophages. Moreover, we have explored OLA-induced epigenetic changes in histone markers and related cytokine production in murine LPS-stimulated murine splenocytes. Murine cells were treated with OLA in the presence or absence of LPS (5 μg/mL) for 18 or 24 h. OLA modulated the oxidative stress and the inflammatory response produced by LPS stimulation in murine peritoneal macrophages, by the inhibition of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IFN-γ, IL-17 and IL-18) and ROS production and the expression of pro-inflammatory enzymes such as iNOS, COX-2 and m-PGES1. These protective effects could be due to the activation of the Nrf-2/HO-1 axis and the inhibition of JAK/STAT, ERK and P38 MAPKs and inflammasome canonical and non-canonical signaling pathways. Moreover, OLA modulated epigenetic modifications throughout histone methylation deacetylation (H3K18ac) and (H3K9me3 and H3K27me) in LPS-activated spleen cells. In conclusion, our data present OLA as an interesting anti-inflammatory and antioxidant natural compound that is able to regulate histone epigenetic markers. Nevertheless, additional in vivo studies are required to further investigate the beneficial effects of this EVOO secoiridoid, which might be a promising epinutraceutical bioproduct for the management of immune-related inflammatory diseases., This research was funded by MINISTERIO DE ECONOMÍA Y COMPETITIVIDAD OF SPAIN, grant number AG-2017-89342-P and JUNTA DE ANDALUCÍA (CTS-259 and FQM-182).

Four caffeoylquinic acid (CQA) derivatives, 5-O-caffeoylquinic acid (1), 3,5-di-O-caffeoylquinic acid (3), 4,5-di-O-caffeoylquinic acid (4), and 3,4,5-tri-O-caffeoylquinic acid (5), have been isolated from Artemisia herba-alba growing wild in Algeria, using the on-line HPLCDADDPPH radical-scavenging detection technique as guidance. In the course of the purification work, the non-frequent (E)-2-(β-D-glucopyranosyloxy)-4-methoxycinnamic acid (2) has also been isolated. The CQAs showed fair-to-good antioxidant activities determined by the DPPH. scavenging assay. The structures of the five isolated compounds were determined by spectroscopic methods. The on-line HPLCDADDPPH technique allowed for a rapid pinpointing of antioxidants in the studied plant, accomplishing the facile guided isolation of the target molecules. Algerian A. herba-alba could be an interesting source of natural antioxidants that deserve further work.

Five new bulky moiety-modified analogues of the sandalwood odorant Polysantol have been synthesized by aldol condensation of appropriate aldehydes with butanone, deconjugative alpha-methylation of the resulting alpha,beta-unsaturated ketones, and reduction of the corresponding beta,gamma-unsaturated ketones. The final compounds were evaluated organoleptically and one of them seemed to be of special interest for its natural sandalwood scent.

The four stereoisomers of (5E)-4,4-dimethyl-6-(2′,2′,3′-trimethylcyclopent-3′-en-1′-yl)-hex-5-en-3-ol, a homologue of the valuable sandalwood-type odorant Polysantol®, were enantiospecifically synthesized from (+)- and (−)-α-pinene, through (−)- and (+)-campholenic aldehyde, by aldol condensation with 3-pentanone, deconjugative α-methylation and reduction. The mixtures of epimeric alcohols obtained after reduction were separated by means of derivatization with (−)-(1S)-camphanic chloride. The enantiomerically pure final products were evaluated organoleptically.

The syntheses of the commercial sandalwood-type odorant Polysantol ® and several structurally related compounds are described. The methodology followed is based on a selective and efficient magnesium-mediated aldol reaction of the starting material, α-campholenic aldehyde and different α-bromoketones. Dehydration of the resulting secondary alcohol and reduction of the carbonyl group allowed the completion of the syntheses of the target molecules in 30–56% overall yields.

Among several sulfonic acids studied (MeSO3H, p-TsOH, H2SO4, ClSO3H, FSO3H), the scarcely used chlorosulfonic acid showed to be an efficient agent for electrophilic olefin cyclizations with internal nucleophilic termination, in a similar manner that is well-established with fluorosulfonic acid. Its availability, lower price and relatively lesser handling problems makes ClSO3H an advantageous cyclizing agent particularly for high-scale applications. The stereochemical outcome of these cyclizations has been rationalized.

A synthesis of the valuable amber-type odorant Ambrox® from labdanolic acid (main diterpenoid of the acid fraction of non-polar extracts of Cistus ladaniferus L.) is reported. The conversion is based on (a) the α,β-dehydrogenation of methyl labdanolate using an organoselenium reagent, (b) subsequent oxidative degradations of the side chain, and (c) final acid-promoted cyclization of the resulting tetranorlabdan-8α,12-diol. The influence of the temperature and solvent in the cyclization of the diol with p-toluenesulfonic acid is also described. Thus, Ambrox® has been obtained by a six-step procedure in 33% overall yield from methyl labdanolate.

Three drimanes, polygodial (2), albicanyl acetate (3) and 7-oxo-8,12-drimen-11-al (5), and two homodrimanes, 13,14,15,16-tetranorlabd-7-en-12,17-dial (6) and 7-oxo-13,14,15,16-tetranorlabd-8(17)-en-12-al (7), were synthesized from (−)-sclareol (1), and their antifeedant, antitumor and antimicrobial properties tested. In most cases, 6 and 7 were found to be more active than 2.

Two new carboxylic acids, 1 and 6 , have been isolated from the aerial parts of Lafuentea rotundifolia Lag. (Scrophulariaceae). The structural determination was performed by spectroscopic methods and chemical correlations, the absolute stereochemistry being established by Mosher's method. Both substances have a fatty acid-type structure with an unusual pattern.

The isomerization of β-caryophyllene (3), under treatment with SeO2, is described. Chemical correlations, between 3 14--hydroxy-β-caryophylllene (6z) from Juniperus oxycedrus, are establised. High resolution 1H NMR spectra and analysis by molecular mechanics of 3, 6 and 14-acetoxy-β-caryophyllene (7) indicate the existence of two conformational isomers, βα and ββ, in each compound. At 35°C, the βα conformer predominates in 3 and 7 but the ββ conformer predominates in 6. The higher precentage of 6ββ possibly derives from an intramolecullar hydrogen bond. The treatment of 3, 6 and 7 with m-CPBA generates, in each case, two diasteromeric 4,5-epoxi-derivatives. The epoxides obtained from 6 have been isolated and analysed separately.

The enantiospecific synthesis of drimenyl acetate (8), a key intermediate in the synthesis of biologically active drimanes, and albicanyl acetate (14), potent fish antifeedant, from sclareol (1), are described. Also a short and efficient synthesis of polygodial (22), from albicanyl acetate (14), is shown.

The synthesis of nor-ambreinolide (2) from cis-abienol (1) was carried out by direct treatment with OsO4-NaIO4 or RuO4-NaIO4. The oxymercuriation-demercuriation of 1 led to a mixture of 8,12-epoxylabdanes (5–17) which was also converted into nor-ambreinolide by treatment with RuO4-NaIO4. The formation pathways of such epoxy derivatives are discussed.

Two routes for preparing Ambrox® (1) from the methyl esters of trans-communic acid (2b) and/or cis-communic acid (3b), via selective degradation of their side chains, stereoselective formation of the tetrahydrofurane ring, and reduction of the axial methoxycarbonyl group, are described.

Short and efficient syntheses of (−)-Ambrox® (12) from (−)-sclareol (1) and (+)-cis-abienol (11) are described. In constrast to previously described procedures, the transformation of 1 to 12, involving in the key step, an oxidative degradation by catalytic osmium tetroxide, in the presence of sodium periodate, has the advantage of using the more suitable sodium borohydride, as the reducing agent. The isolation and characterization of some reaction intermediates allowed us to confirm the degradation mechanism.

A mixture of the methyl esters of communic acids ( 3b, 4b, 5b ) was used in the synthesis of the ambergris-type odorants Ambrox ® ( 1 ) and ambracetal ( 2 ). Both syntheses involve methyl ketone 7 as the key intermediate.

The replacement of some synthetic food antioxidants by safe natural antioxidants has fostered research on the screening of raw materials to find new vegetable sources of antioxidants. In this study the antioxidant activity of eight wild-growing Colombian plants was assessed by four complementary assays.An evaluation of the antioxidant activity of ten ethanolic extracts from Baccharis chilco, Cinnamomum triplinerve, Ilex laurina, Lachemilla orbiculata, Lepechinia conferta, Quercus humboldtii, Rubus urticifolius and Tephrosia cinerea was carried out. Furthermore, the total phenolic content was determined by the Folin-Ciocalteu method, and the relationship between phenolic content and activity was also statistically investigated. Cinnamomum triplinerve, L. conferta and I. laurina were found to have the highest phenolic contents. Baccharis chilco, C. triplinerve, I. laurina, L. conferta, Q. humboldtii and R. urticifolius showed higher radical-scavenging activity (DPPH and superoxide assays) than commercial rosemary oleoresin (reference). Lachemilla orbiculata and R. urticifolius showed higher antioxidant activity (β-carotene-bleaching test) than the reference. The protection factor of all studied plant extracts was below that of the reference according to the Rancimat test.On the basis of the results obtained, C. triplinerve, Q. humboldtii and R. urticifolius seem to be the most promising species for further investigation in order to identify the compounds responsible for their activity.

Polyphenols, such as rosmarinic acid, are widely distributed natural products with relevant antioxidant activity. Oxidative stress plays an important role in the pathogenesis of a number of disorders. Here, we report on the synthesis and biological effects of the polyphenolic esters hydroxytyrosyl gallate (1), hydroxytyrosyl protocatechuate (2) and hydroxytyrosyl caffeate (3), structurally related to rosmarinic acid. The three compounds showed a greater free radical scavenging activity than their precursors and also than rosmarinic acid. Esters 1 and 3 significantly reduced thrombin-evoked platelet aggregation, which is likely mediated to the attenuation of thrombin-stimulated Ca(2+) release and entry. The three compounds reduced the ability of platelets to accumulate Ca(2+) in the intracellular stores, probably by enhancing the Ca(2+) leakage rate and reduced store-operated Ca(2+) entry in these cells. These observations suggest that the structurally-simplified analogs to rosmarinic acid, compounds 1 and 3, might be the base of therapeutic strategies to prevent thrombotic complications associated to platelet hyperaggregability due to oxidative stress.

Reactions of methyl 12,13-epoxy-cis-communates ( 3 , 4 ) and methyl 12,13-epoxy-trans-communates ( 5 ), 6 ) with BF3:etherate at 0°C are reported. They occur in a stereoselective and stereospecific way yielding mainly C-12 oxygenated pimaranes. When the reaction was carried out from 5 and 6 two tetracyclic ketones ( 17 , 18 ) were also isolated. Reaction mechanisms and stereochemical implications are discussed.

The dichloromethane and ethanol extracts of Olea europaea wood (picual olive cultivar) were screened for antioxidant activity, determined by the DPPH free radical scavenging assay. The ethanol extract displayed potent antioxidant activity. (c) 2005 Elsevier B.V. All rights reserved.

Leaf and (unripe and ripe) berry essential oils of Juniperus oxycedrus ssp. badia (H. Gay) Debeaux grown wild in Spain have been analysed by capillary GC and GC-MS in combination with retention indices. A seasonal investigation of both leaf and berry oils was also performed. Among the approximately 80 constituents investigated (representing 90-98% of the oils) 60-68 were identified (80-97% of the oil composition). The leaf oils were mainly composed of alpha-pinene (40-57%) and manoyl oxide (5-10%). The (unripe) berry oils were dominated by alpha-pinene (65%) with moderate amounts of myrcene, limonene, germacrene D or gamma-muurolene. Several differences in yields and chemical composition from a qualitative and quantitative point of view were detected when comparing all the oil samples analysed. In addition, two oil samples were examined, but found inactive, against the replication of HIV-1(III(B)) and HIV-2(ROD) in cell culture, whereas the samples were toxic for the cells at a 50% cytotoxic concentration of 106 and 123 microg/ml, respectively.

This review summarizes the chemical composition reported up to date on Laurus nobilis L. (Lauraceae), an evergreen shrub or tree cultivated for its aromatic leaves and ornamental interest. It has been focused on non-volatile phytochemicals such as sesquiterpene lactones, flavonoids and proanthocyanidins, among others. Moreover, biological activities of laurel extracts and pure compounds have also been reviewed.