Stilbene chemical synthesis

The active stilbene agents, reported in this chapter, derived from either marine or terrestrial sources tested in clinics have a unique chemistry that offers valuable information for their use as compounds for further chemical synthesis of more potent chemotherapeutic drugs against a variety of cancers. The stilbenes also possess the antioxidative, anti-inflammatory, and estrogenic effects and chemo-preventive activities. A challenging goal is the search for more active natural products as therapeutic agents in cancer and other diseases. This search should be continued until a novel and very effective compound is found. 

The electrophilic bromination of ethylenic compounds, a reaction familiar to all chemists, is part of the basic knowledge of organic chemistry and is therefore included in every chemical textbook. It is still nowadays presented as a simple two-step, trans-addition involving the famous bromonium ion as the key intermediate. T]nis mechanism was postulated as early as the 1930s by Bartlett and Tarbell (1936) from the kinetics of bromination of trans-stilbene in methanol and by Roberts and Kimball (1937) from stereochemical results on cis- and trans-2-butene bromination. According to their scheme (Scheme 1), bromo-derivatives useful as intermediates in organic synthesis... 

Annelation of racemic intermediate leading to racemic [n]helicene Larsen and Bechgaard reported the nonphotochemical synthesis of racemic [5]-and [9]thiahelicenes, relying on monoannelations of stilbene precursors [62], Electrochemical or chemical (FeCl3) oxidation was used in place of usual photooxidation, to provide thiahelicenes in 20-65% yields. For example, racemic [9]thiahe-licene 9 was obtained in —60% yield from stilbene 8 by oxidation with FeCl3 in methylene chloride (Fig. 15.3) a similar result was obtained by classical photooxidation of stilbene 8 [51]. 

One of the most relevant and extensively studied stilbene is trani-resveratrol (3,5,4 -trihydroxystilbene), a phytoalexin produced by grapevines in response to fungal infection, particularly Botrytis cinerea. Synthesis of resveratrol in grape berries is mainly located in the skin cells and is absent or low in the fruit flesh. In nature, resveratrol exists in two isomeric forms (cis- and frani -conflgured) in the free as well as in 6-glucoconjugated form. The 3-0-6-D-glucosides of cis- and trans-resveratrol cis-and trans-conflgured are called piceids. The chemical structures of resveratrol and further stilbenes are depicted in Fig. 9C.6. 

Samples used in this work are the mixtures of poly (vinyl methyl ether) (PVME, 1.0 X 105, M = 2.5) and polystyrene (PS) derivatives. To be able to induce phase separation by light, the PS component was chemically labeled with photoreactive groups, either with anthracene (A) or rra/i -stilbene (S). The synthesis procedure of these polymers was published elsewhere (8,16). 

Because of the chemical stability of phenyl moiety of 1,2-diphenylethylene, stilbene is not a suitable starting compound for synthesis of stilbene derivatives. In order to form more complex molecules, it is necessary to introduce more reactive functional groups. 

Chapters 3 and 4 and this chapter clearly demonstrated the rich array of photochemical and photophysical phenomena associated with stilbenes and their related substituted analogues. Because these compounds are available through their synthesis (Chapters 1 and 2), and are thermally and chemically stable, they are taking on an increasingly prominent role in the area of photochemical and biophysical investigations and multiple applications. 

A combination of classical and modem synthesis methods allowed chemists to prepare thousands of new stilbenes, which possess a variety of chemical and physical properties, in solution, polymers, and on templates. The synthesized compounds show the rich chemistry involved in multiple reactions such as halogenation, oxidation, reduction, addition, substitution, polymerization, complexation, and so on. 

Figure 14.6. Traceless linker strategy for the solid-phase synthesis of unsymmetrical trans-stilbenes. Adapted with permission from Ref. 32. Copyright 2010 American Chemical Society.

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