411233-11-9

Upstream product

• 108-05-4 vinyl acetate 
• 501-36-0 (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol 
• 108-24-7 acetic anhydride 
• 18259-14-8 (E)-1-(4'-acetoxyphenyl)-2-(3,5-dimethoxyphenyl)ethene 
• 99-10-5 3,5-Dihydroxybenzoic acid 
• 2628-16-2 p-acetoxystyrene 
• 192182-54-0 3,5-dimethoxyphenylboronic acid 
• 1432450-00-4 (E)-4-(3,5-bis(benzyloxy)styryl)phenyl acetate 
• 28917-44-4 3,5-dibenzyloxylbenzoyl chloride 
• 28917-43-3 3,5-dibenzyloxybenzoic acid 
• 58605-10-0 methyl 3,5-bis(benzyloxy)benzoate 
• 2150-44-9 1-carbomethoxy-3,5-dihydroxybenzene 
• 228997-09-9 3,5-bis(methoxymethoxy)benzoic acid 

Downstream Products

• 501-36-0 (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol 
• 1622988-44-6 (E)-4-(3,5-bis((triisopropylsilyl)oxy)styryl)phenol 
• 1622988-45-7 4-[(E)-3,5-bis(triisopropylsilyloxy)styryl]phenyl (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoate 
• 1622988-43-5 (E)-4-(3,5-bis((triisopropylsilyl)oxy)styryl)phenyl acetate 

Relevant academic research and scientific papers

Regioselective lipase-catalyzed synthesis of 3-o-acyl derivatives of resveratrol and study of their antioxidant properties

One of the approaches to increasing the bioavailability of resveratrol is to protect its 3-OH phenolic group. In this work, regioselective acylation of resveratrol at 3-OH was achieved by transesterification with vinyl acetate catalyzed by immobilized lipase from Alcaligenes sp. (lipase QLG). The maximum yield of 3-O-acetylresveratrol was approximately 75%, as the lipase also catalyzes its further acetylation affording the diester 3,4′-di-O- acetylresveratrol and finally the peracetylated derivative. Long saturated and unsaturated fatty acid vinyl esters were also effective as acyl donors with similar regioselectivity. In contrast, lipase B from Candida antarctica catalyzes the acylation of the phenolic group 4′-OH with 80% yield and negligible formation of higher esters. The analysis of the antioxidant properties showed that the Trolox equivalent antioxidant capability (TEAC) values for the acetyl and stearoyl derivatives at 3-OH were, respectively, 40% and 25% referred to resveratrol. The addition of an acyl chain in the 3-OH position caused a higher loss of activity compared with that at the 4′-OH.

Synthesis of amphiphilic resveratrol lipoconjugates and evaluation of their anticancer activity towards neuroblastoma SH-SY5Y cell line

Resveratrol, a polyphenol present in grapes and other edible plants, possesses several important pharmacological activities, including anticancer activity. Nevertheless, its therapeutic use is still limited because of some unfavourable physicochemical and pharmacokinetic properties, mainly, poor cellular uptake and too rapid metabolism resulting in elimination from the body. To meet these drawbacks, some resveratrol conjugates would be useful, which would possess improved stability, uptake and bioavailability than the lead compound, and the ability to release it once it is internalized into the cell. In this paper we report a synthetic strategy which allowed us to obtain new amphiphilic resveratrol derivatives starting from different selectively protected resveratrol phosphoramidites or even from the resveratrol triphosphoramidite. Specifically, resveratrol was conjugated through phosphate bridge(s) to different lipophilic groups related to membrane lipids, such as cholesteryl or diacylglycero moieties. All the new lipoconjugates were tested towards human neuroblastoma SH-SY5Y cells and proved to be significantly more active than resveratrol, with a concentration-dependent activity.

Immobilized Lipase Based on Hollow Mesoporous Silicon Spheres for Efficient Enzymatic Synthesis of Resveratrol Ester Derivatives

Enzymatic esterification of resveratrol is crucial for its potential application in lipophilic foods and drugs. However, the poor activity of the free enzyme hinders the reaction. In this work, the highly efficient enzymatic synthesis of resveratrol ester derivatives was achieved by immobilized lipase on hydrophobic modified hollow mesoporous silicon spheres (HMSS-C8). We preliminarily explored the use of Candida sp. 99-125 lipase (CSL) for the acylation of resveratrol, with a regioselectivity toward 3-OH- over 4'-OH-acylation. HMSS-C8 provided ideal accommodation for CSL with a loading capacity of up to 652 mg/g. The catalytic efficiency of CSL@HMSS-C8 was 15 times higher than that of free CSL, and the conversion of resveratrol reached 98.7% within only 2 h, which is the fastest value recorded in the current literature. After 10 cycles, the conversion remained up to 86.3%. Benefiting from better lipid solubility, the relative oxidation stability index values of oil containing monoester derivatives were 43.1%-68.8% and 23.9%-33.2% higher than that of refined oil and oil containing resveratrol, respectively. This research provides a new pathway for efficient enzymatic synthesis of resveratrol ester derivatives and demonstrates the potential application of resveratrol monoester derivatives as a group of excellent lipid-soluble antioxidants.

Biological activity of acetylated phenolic compounds

In recent years an effort has been made to isolate and identify biologically active compounds that are included in the Mediterranean diet. The existence of naturally occurring acetylated phenolics, as well as studies with synthetic ones, provide evidence that acetyl groups could be correlated with their biological activity. Platelet activating factor (PAF) is implicated in atherosclerosis, whereas its inhibitors seem to play a protective role against cardiovascular disease. The aim of this study was to examine the biological activity of resveratrol and tyrosol and their acetylated derivatives as inhibitors of PAF-induced washed rabbit platelet aggregation. Acetylation of resveratrol and tyrosol was performed, and separation was achieved by HPLC. Acetylated derivatives were identified by negative mass spectrometry. The data showed that tyrosol and its monoacetylated derivatives act as PAF inhibitors, whereas diacetylated derivatives induce platelet aggregation. Resveratrol and its mono- and triacetylated derivatives exert similar inhibitory activity, whereas the diacetylated ones are more potent inhibitors. In conclusion, acetylated phenolics exert the same or even higher antithrombotic activity compared to the biological activity of the initial one.

Synthesis and skin gene analysis of 4′-acetoxy-resveratrol (4AR), therapeutic potential for dermal applications

Resveratrol (RV) 1, a plant polyphenol, has proven effective in commercial products yet drawbacks include low bioavailability due to rapid metabolism. Structural modifications have led to a 4′-acetoxy analog 2 (4AR) now produced using a selective one-step esterification reaction. The one-step synthesis is shown together with expression of skin genes using human dermal models to establish 4AR 2 benefits to skin health. 4AR 2 at 1% in qPCR experiments using a human skin model significantly increased gene expression of the anti-aging factor, SIRT 1 by over 3.3-fold, extracellular matrix proteins collagen III, IV, elastin and tissue inhibitors of metalloproteinases (TIMP 1, 2), anti-oxidants CAT, LOX, superoxide dismutase (SOD 1, 2), metallothioneins (MT1H, MT1H), skin aging biomarkers fibrillin (FBN1), laminin (LAMB1), proliferating cell nuclear antigen (PCNA), skin growth factors (HBEGF, IGF1, NGF and TGF). 4AR 2 also decreased gene expression of inflammatory and skin-aging molecules (IL-1, IL-6, IL-8, COX-2, TNGRSF) and S100 calcium binding proteins A8, A9. These findings suggest that 4AR 2 has potential for topically treatment and prevention of skin aging.

NEW USES OF LIPOPHENOLIC COMPOUNDS

The present invention relates to compound of formula (I) : wherein R is O-R3 or R1 and R2 are identical or different and are each independently H, (C1-C6)alkyl, -CO-(C1-C21)alkyl or -CO-(C11-C21)alkenyl group, provided that at least one of R1 or R2 is H or (C1-C6)alkyl, R3 is a -CO-(C11-C21)alkyl or -CO-(C11-C21)alkenyl group, or its pharmaceutically acceptable salts, racemates, diastereoisomers, enantiomers, or mixtures thereof, for use in prevention and/or treatment of a disease or disorder linked to an exacerbated vascular, lymphatic or mucosal permeability.

Resveratrol-Linoleate protects from exacerbated endothelial permeability via a drastic inhibition of the MMP-9 activity

Gelatinolytic matrix metalloproteinases (MMP-2, -9) play a critical role not only in mammals physiology but also during inflammation and healing processes. The natural stilbenoid, resveratrol (RES), exhibits potent antioxidant effects, in a hormetic mode of action, and is known to inhibit MMP-9. However, RES administration exhibits major issues, including poor bioavailability and water solubility, hampering its potential therapeutic effect in vivo. In the present study, we synthesized and evaluated five novel RES–lipid conjugates to increase their cell membrane penetration and improve their bioavailability. The best in vitro MMP-9 inhibitory activity of RES–lipids conjugates was observed with RES-linoleic acid (LA) (5 μM), when dissolved in a natural deep eutectic solvent (NADES), composed of an equimolar content of 1,2-propanediol:choline chloride (ChCl):water. The inhibition of MMP-9 expression by RES-LA in activated THP-1 monocytes, was, at least due to the deactivation of ERK1/2 and JNK1/2 MAP kinase signaling pathways. Moreover, RES-LA exhibited a strong effect protecting the TNF-α-induced exacerbated permeability in an HUVEC in vitro monolayer (by 81%) via the integrity protection of intercellular junction proteins from the MMP-9 activity. This effect was confirmed by using several complementary approaches including, the real-time monitoring of trans-endothelial electric resistance (TEER), the Transwell HUVEC permeability level, the microscopic examination of the platelet endothelial cell adhesion molecule-1 (CD31/PECAM-1) integrity as well as the fluorescence in intercellular spaces. Consequently, following this strong in vitro proof-of-concept, there is a need to test this promising RES–lipid derivative compound to control the pathological endothelial permeability in vivo.

A facile and rapid access to resveratrol derivatives and their radioprotective activity

A facile and rapid access to resveratrol derivatives has been achieved based on palladium-catalyzed oxidative Heck reaction of aryl boronic acids with styrenes followed by demethylation in moderate to good yields. A series of resveratrol derivatives with various functional groups has been synthesized easily. The radioprotective activity of synthesized compounds has also been evaluated using rat thymocytes. The results revealed that some resveratrol derivatives efficiently protected the thymocytes from radiation-induced apoptosis.

Synthesis and biological evaluation of novel resveratrol-NSAID derivatives as anti-inflammatory agents

Long-term use of nonsteroidal antiinflammatory drugs (NSAIDs) may cause serious side effects such as gastric mucosal damage. Resveratrol, a naturally dietary polyphenol, exhibited anti-inflammatory activity and a protective effect against gastric mucosa damage induced by NSAIDs. In this regard, we synthesized a series of resveratrol-based NSAIDs derivatives and evaluated their anti-inflammatory activity against nitric oxide (NO) overproduction in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We identifiedmono-substituted resveratrol- ibuprofen combination 21 as the most potent anti-inflammatory agent, which is more active than a physical mixture of ibuprofen and resveratrol, individual ibuprofen, or individual resveratrol. In addition, compound 21 exerted potent inhibitory effects on the LPS-induced expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Furthermore, compound 21 significantly increased the survival rate in an LPS-induced acute inflammatory model and produced markedly less gastric damage than ibuprofen. It was found that compound 21 may be a potent anti-inflammatory agent for the treatment of inflammation-related diseases.

NEW LIPOPHENOL COMPOUNDS AND USES THEREOF

The present invention relates to a compound of formula (I) wherein: - i is 0 or 1; j is 0 or 1; k is 0 or 1; - R1 and R2 are in particular H, (C1-C12)alkyl, or a group of formula C(O)R; - R is a, linear or branched, alkyl radical, comprising at least 19 carbon atoms; - R3 is H and k=0 when j=1; or, when j=0, R3 is -C(O)R or -L-C(O)R; - L, U and L" are linkers; wherein, when j=0, at least one of the groups R1; R2 and R3 comprises a radical R.