Stilbenoids isolation

In the photoisomerization of l-(2-anthryl)-2-phenylethene [232-234] and l-(2-naphthyl)-2-phenylethene [235-237] 95, the s-cis/s-trans conformational isomerism plays an important role. (Z)-l-(2-Naphthyl)-2-phenyl-ethene is isolated in 70% yield in fluorenone-sensitized isomerization of the ( )-isomer (Sch. 39) [238,239]. The photochemical behavior of related (E)-stilbenoids (96-98) has been reported (Sch. 40) [240]. The direct and sensitized photoisomerizations of (Z)-styrylferrocene in benzene have also been reported [241]. 

Stilbene system is widely distributed in nature where it is found in a variety of compounds that exhibit therapeutic roles in different fields, including cancer treatment. Albeit stilbene itself is not found in nature, polyhydroxylated stilbenoids (stilbenes and bibenzyls) have been isolated from several medicinal plants [1]. 

The work on stilbenoids was reviewed by Gorham in 1995 [4]. Herein, we review the recent progress in the studies of stilbenoids with respect to their structure, distribution, extraction and isolation, technologies used in structure identification, synthesis and biosynthesis, and the last but not the least, bioactivities. The coverage of the new structures is from 1994 (especially those that have not been covered by Gorham [4]) to June 2006 (the references in 2006 may not be collected thoroughly as some of them might have not been included in the databases yet). 

In the past 12 years, about 800 novel Stilbenoids have been isolated and identified. According to their structural characteristics, they are classified into six types, namely, stilbenes, bibenzyls, bisbibenzyls, phenanthrenoids, stilbene oligomers and other stilbenoids. 

Accompanied by stemofurans A-K (92-102), the bibenzyls and stilbostemins A-F (132-137), were also isolated fi-om Stemona collinsae roots together with five known derivatives -the stilbenes pinosylvin and 4-methylpinosylvin and the dihydrophenanthrene stemanthrene D (359) [57]. Stilbostemin B (133) and D (135) have been previously isolated from Stemona tuberosa [75]. The consecutively designated stilbostemin G (138) was isolated from Stemona cf. pierrei [76]. It became apparent that the stilbenoids of Stemona genus can be characterized mainly by the C-methylation of aromatic rings and the formation of phenylbenzofurans. 

The carexanes (794-796) with a tetracyclic skeleton have been isolated from the leaves of Carex distachya. They seem to be derived from the coupling of the prenyl moiety with a stilbenoid structure. A plausible biogenetic pathway for the formation of carexanes has been proposed (Scheme 5) [346],... 

It is the development of separation and identification techniques that makes the isolation and elucidation of the stilbenoids applicable. Silica gel is still the most commonly used material of the stationary phase. However, many other materials possessing better resolution or different isolation mechanisms have also been widely applied, e.g. Sephadex LH-20 [299 etc.], ODS Cis [208,299 etc.], MCI gel CHP20P, Toyopearl HW-40F [20,27,114,242,354], especially the former two. The combination use of the materials is efficient for the separation of the structures with high similarity and high polarity such as stilbene glucoside sulfates (34—43) [27]. 

Other methods have also been successfully employed in the isolation procedure of stilbenoids, including MPLC [209,299,326], preparative TLC [208,277,299], centrifugal partition chromatography (CPC) [359,360] and the support-free technique of multilayer coil countercurrent chromatography (MLCCC) [32]. A method based on capillary electrophoresis with electrochemical detection (CE-ED) was employed for the determination of oligomeric stilbenes found in the roots of Caragana species [361]. 

The anti-virus activity research concerning stilbenoids mainly focuses on HIV. Glepidotin D (162) was isolated from the leaves of Glycyrrhiza lepidota as the compound responsible for the anti-viral activity with an EC50 of 2.0 g/ml and an ICso of 5.0 //g/ml, which excludes the need for further study [98]. 

Pd-catalyzed cross-coupling reactions were studied in one-pot multicatalytic processes to synthesize disubstituted alkenes and alkanes from carbonyl derivatives [68]. The use of Cu-catalyzed methylenation reactions was the key starting reaction to produce terminal alkenes that are not isolated but submitted to further structure elongation (hydroboration followed by Suzuki cross-coupling) (Figure 1.13). These processes have been used to synthesize methoxylated ( )-stilbenoids (i.e., ( )-1,3-dimethoxy-5-(4-methoxystyryl)benzene). 

Synthesis of a number of antifungal stilbenoids can be induced by elicitation with fungal preparations or other factors such as UV light. A family of phytoalexins from mulberries (Moms spp., Moraceae) possess stilbene structures (Fig. 10.9) (Coxon, 1982). The moracins were isolated from shoots of Moms alba infected with Fusarium solani f. sp. mori and were not present in detectable quantities in uninfected tissue. Two additional compounds, oxyresveratrol (10) and 4 -prenyloxyresveratrol (Fig. 10.4), were isolated from fungus-infected xylem extracts of mulberry. Although oxyresveratrol (10) (Fig. 10.4) occurs in heartwood of mulberry, this compound is formed in the sapwood as a phytoalexin. Two similar compounds, broussonin A and B (14, 15), are found in the shoots of paper mulberry (Broussonetia papyrifera, Moraceae) infected with the same fungus (Coxon, 1982 Kuc, 1992). 

Two new resveratrol pentamers, named amurensins E 56 and F 57, have been isolated from Vitis amurensis [34]. The isolation and structural elucidation of a hexamer vaticanol D 58 and a heptamer vaticanol J 59 from Vatica rassak have been reported [29]. An octamer vateriaphenol A 60 from Valeria indica was reported by Ito and coworkers, and it is the largest molecules of stilbenoids [35]. 

Stilbenoids represent a group of important natural products in the plant kingdom. The developments of modem analytical methods accelerate the discovery of these compounds, and to this day more than 1,000 stilbenoids have been isolated. For the stilbenes, bibenzyls, and phenanthrenes, these three groups shared the feature of their nucleus with hydroxyls, methyl, methoxy, prenyl, geranyl, glycosyl, etc., substituents. The oligostilbenes and bisbibenzyls are formed by polymerization of stilbene and bibenzyl units, and the diverse polymerized patterns produced their... 

Stilbenoids are highly inducible in leaves using a number of chemicals, UV-C treatment, and infectious agents [25]. To date, the majority of stilbenoids from leaves have been identified from stressed leaves. In some of the preliminary studies by Langcake and Pryce using leaves infected by Botrytis cinerea, the main stilbenoids detected were -resveratrol, -a-viniferin (Fig. 73.2), and a-viniferin [26]. The res-veratrol dehydrodimer, 5-viniferin, and piceids were detected in leaves induced by UV irradiation [27,28]. More recently, Mattivi et al. isolated and identified 14 stilbenoids from the leaves of a hybrid V. vinifera infected with Plasmopara viticola [23]. These compounds included two new dimers and two new to V. vinifera -co-viniferin. 

From the roots, five stilbenoids have been isolated, including resveratrol, -viniferin (dimer), gnetin H (trimer), hopeaphenol, and r-viniferin (tetramers) [39]. 

The phytochemical diversity of C. saliva is well illustrated by more than 500 com-potmds isolated from this plant, encompassing all major classes of phytochemicals (polyketides, terpenoids, alkaloids, flavonoids, stilbenoids, oxylipins). Undoubtedly, the most important and peculiar secondary metabolites of C. saliva are cannabinoids, a class of mono- to tetracyclic C21 (or C22) meroterpenoids encompassing more than 100 members. These compounds are synthesized in secretory cells of glandular trichomes, most concentrated in unfertilized female cannabis flowers prior to senescence. A number of detailed accounts on the cannabinoid chemistry have been reported in the literature [6-8], also recently by Appendino et al. [9]. In this paragraph, we will provide an updated, although not comprehensive, account of the chemistry of this fascinating class of secondary metabolites. 

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