Stilbene derivatives resveratrol

Stojanovic S, Brede O. (2002) Elementary reactions of the antioxidant action of trans-stilbene derivatives Resveratrol, pinosylvin and 4-hydroxystilbene. Phys Chem Chem Phys A 757-764. 

Addition. Resveratrol. The biosynthetic pathway to resveratrol diverges from the flavonoid pathway after the third malonyl-CoA condensation. Cyclization of the common polyketide intermediate catalyzed by resveratrol synthase yields the stilbene derivative resveratrol, whereas the same intermediate catalyzed by chal-cone synthase yields the common flavonoid precursor chalcone (Fig. 6.8). Resveratrol, well known as a functional food ingredient (e.g., grape skin, red wine) with strong antioxidant properties (cardiovascular protection), and its 3-glucopyranoside piceid turned out to be also present in the skin of tomato fruits, S. lycopersicum (Ragab et al. 2006). 

Resveratrol is another type of polyphenol, a stilbene derivative, that has assumed greater relevance in recent years as a constituent of grapes and wine, as well as other food products, with antioxidant, anti-inflammatory, anti-platelet, and cancer preventative properties. Coupled with the cardiovascular benefits of moderate amounts of alcohol, and the beneficial antioxidant effects of flavonoids, red wine has now emerged as an unlikely but most acceptable medicinal agent. 

When the dehydration of 39 was carried out (H3PO4 or DMSO under reflux) instead of its dehydroxylation, a different class of stilbene derivatives, such as pinosilvine 44, resveratrol 45 or piceatannol 46, were easily obtained . From these compounds, resver-atrol has shown very potent anticancer properties in vivo, this activity being proven in rats . 

It is widely accepted that polyphenols in wine are responsible for beneficial health effects (Sun et al. 2006). Particularly fran.y-resveratrol has been intensively studied and marked biological activities with regard to the prevention of cardiovascular disease and cancer have been reported (Ito et al. 2003). Other stilbenes also have properties similar to those of fran.y-resveratrol. Therefore, monitoring new stilbene derivatives in wine is of particular relevance (Guebailia et al. 2006). 

Nowadays, LC-MS systems have been often applied to identify and quantify stilbenoids, for example, bibenzyls in Scorzonera humilis [84], phenanthrenes of Dendrobium chrysanthum [201], resveratrol oxidative products [257] and stilbenes derivatives [363]. 

It is interesting to note that in vitro incubations of 1 with horseradish peroxidase [108] as well as with growing B. cinerea cultures [106] and B. cinerea culture medium filtrates [107] have yielded a unique resveratrol oligomer known as the resveratrol trans-dehydrodimer (42). This dimer shares a similar structural design with the more common plant-derived resveratrol dimer, f-viniferin (11). It has been proposed that the B. cinerea mediated transformation of 1 to 42 may be facilitated by other stilbene oxidizing enzymes such as copper-containing laccases [106,107]. 

Some stilbenoids from the roots of Vitis thunbergii, such as vitisinols B, C, D (772, 773, 576), (+)-e-viniferin (445), (-)-viniferal (771), ampelopsin C and (+)-vitisin C (700), displayed strong free radicalscavenging activities (ICsos 2.8 to 6.6 //M) [245]. The antioxidant capacity of /rafts-e-viniferin (445) has also been evaluated and compared with those of resveratrol (1) and synthetic stilbene derivatives [504]. 

A rapid analysis of resveratrol, trans-E-viniferin, and trans-5-viniferin from downy mildew-infected grapevine leaves by liquid chromatography-atmospheric pressure photoionization mass spectrometry was performed [168]. The characterization of unknown stilbene derivatives such as six resveratrol dimers, two dimethylated... 

Many stilbene derivates (stilbenoids) are naturally present in plants. The most widely distributed stilbenoids are resveratrol, combretastatins, and pterostilbene. These agents are derived from terrestrial plants, microorganisms, marine organisms, and animals [1,2]. This chapter is a brief review on diverse biological activities of stilbenes in cells, organs, and animals. 

The coupling of iodo aryls with various olefins was conducted in the presence of palladium chloride (2.0 mol%) at ambient temperature under ultrasonic irradiation in water with yields between 43 and 90% [154], In situ formation of palladium nanoparticles was confirmed by transmission electron microscope and X-ray diffraction analyses, and the palladium nanoparticles could be reused for multiple reactions without significant loss of activity. Biologically relevant stilbene derivates, such as resveratrol, piceatannol and pinosilvine, were efficiently prepared with high regioselectivity and complete stereocontrol (TONS up to 10 , 0.01 to 0.50 mol% catalyst) [148], The activity of the oxime-derived palladacycle catalysts was compared in neat water with a DMF-water mixture, with similar... 

Strawbeny Frost grape/ overexpression CaMV 35S and flll/Vst3 Stilbene synthase Resveratrol Higher ciimamate, coumarate, and ferulate derivatives/ lower flavonols [69] c 3 rx <-i- o 3... 

Dormez D, Jeandet P, Qement C, Conrot E (2009) Bioproduction of resveratrol and stilbene derivatives by plant cells and microorganisms. Trends Biotechnol 27 706-713. doi 10.1016/j.tibtech.2009.09.005... 

Stilbene derivatives were obtained from Calligonum leucocladum, and the structures were determined as (El-resveratrol 3-(6-gaUoyl)-0-p-D-glucopyranoside. 

The green grape skin is also capable of synthesizing phytoalexins in response to an infection (Langcake and Pryce, 1977). These stilbenic derivatives (trans-resveratrol and its glycoside, trans-piceid, dimer e-viniferin, a-viniferin trimer, /S-viniferin tetramer) have fungicidal properties (Figure 10.24). 

The Fujiwara-Moritani reaction enables the coupling of alkenes with arenes under oxidative conditions—also named oxidative Heck reaction (for the mechanism, see Ref [ 29]) Garcia-Rubia et al. used this Pd"-catalyzed oxidative direct C-H alkenylation to produce /rans-stilbene derivatives.As exemplified by their synthesis of pterostilene (Scheme 5-45), a partially methylated resveratrol derivative, a 2-pyridyl sulfinyl group efficiently promotes the Pd"-catalyzed ortho C-H olefination of arenes and can be readily removed or transformed into a thiol group. 

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

Stilbenes have a 1,2-diphenylethylene as their basic structure (C6-C2-C6). Resve-ratrol, the most widely known compound, contains three hydroxyl groups in the basic structure and is called 3,4, 5-trihydroxystilbene. In plants, piceid, the glucoside of resveratrol, is the major derivative of resveratrol. Stilbenes are present in plants as cis or trans isomers. Trans forms can be isomerized to cis forms by UV radiation (Lamuela-Raventos and others 1995). 

Members of the CHS/STS family of condensing enzymes are relatively modest-sized proteins of 40-47 kDa that function as homodimers. Each enzyme typically reacts with a cinnamoyl-CoA starter unit and catalyzes three successive chain extensions with reactive acetyl groups derived from enzyme catalyzed decarboxylation of malonyl-CoA.11 Release of the resultant tetraketide together with or prior to polyketide chain cyclization and/or decarboxylation yields chalcone or resveratrol (a stilbene). Notably, CHS and STS catalyze identical reactions up to the formation of the intermediate tetraketide. Divergence occurs during the termination step of the biosynthetic cascade as each tetraketide intermediate undergoes a distinct cyclization reaction (Fig. 12.2). 

The relative molecular simplicity of combretastatins and resveratrol, associated with their important anticancer properties, offers promises for the rational design of new chemotherapeutic agents. The interest in these compounds is evident from the great number of papers published every years, covering various aspects, chemical and biological. For this reason in this paper the attention will be focused on Combretastatins. The majority of compounds reported in the paper are in fact considered their derivatives or analogues, albeit some of them, e.g. 3,4,5-trimethoxy-4 -substituted stilbenes have been considered resveratrol analogues. 

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