Efficient Synthesis of Natural Polyphenolic Stilbenes: Resveratrol, Piceatannol and Oxyresveratrol

Abstract

Natural trans polyphenolic stilbenes were known to have numerous remarkable biological properties including beneficial effects on patients with cancers, cardiovascular diseases, viral infections, diabetes, dementia, and central nervous system (CNS) disorders. Among them, resveratrol, piceatannol and oxyresveratrol are recognized to be the representatives of trans-polyphenolic stilbenes (Fig. 1).Resveratrol (trans-3,4Ј,5-trimethoxystilbene) is a phytoalexin isolated from more than 70 plant species such as grapes, peanuts, and berries.1) It is now commercially produced from the roots of Polygonum cuspidatum, a plant used in traditional Chinese medicine for centuries. The biological activity of resveratrol has been well documented in recent years through a number of physiological and pharmacological studies which indicate that resveratrol plays an important role in prevention of cancers, 2-5) heart diseases, 6) neurodegenerative diseases 7) and inflammations. 8) Moreover, the radical scavenging, 9) antiviral, 10) antioxidant, 11) lipid modification 12) as well as platelet aggregation inhibition activities 13) associated with resveratrol have also been reported. Recently, resveratrol has been shown to extend lifespan of yeasts, Caenorhabditis elegans and Drosophila melanogaster through activation of sirtuins (SIRT-1, 2), a nicotinamide adenine dinucleotide (NAD) dependent histone deacetylase that has been shown to directly correlate with cellular longevity, 14) and to improve health and survival of mice on a high-calorie diet. 15)Piceatannol (trans-3,3Ј,4Ј,5-tetramethoxystilbene) is a tetrahydroxystilbene and a close analog of resveratrol with an additional aromatic hydroxyl group. It has been isolated from grapes together with resveratrol and several other traditional Chinese herbs. 16,17) Studies showed that piceatannol inhibits several tyrosine kinases involved in cell proliferation. 18-21)The anti-tyrosinase activity of piceatannol (IC 50 ϭ1.53 mM) was significantly higher than that of resveratrol (IC 50 ϭ 63.2 mM). In addition, recent studies indicated that the cancer preventative agent resveratrol is converted to anticancer agent piceatannol by cytochrome P450 enzyme CYP1B1 22) and piceatannol protects PC12 cells from hydrogen-peroxideand peroxynitrite-induced apoptosis by blocking the activation of c-Jun N-terminal kinase (JNK) and the down-regulation of Bcl-XL. 23)Oxyresveratrol (trans-2Ј,3,4Ј,5-tetramethoxystilbene), available from Morus alba Linne Artocarpus lakoocha Roxb and mulberry wood, is another hydroxylated analog of resveratrol with high similarity. It has been known that oxyresveratrol is transported to tissues at high rates resulting in a bioavailability of about 50%.24) Pharmacological studies have demonstrated that oxyresveratrol can be used as an active ingredient in dermatology, 25,26) and exhibiting potent inhibitory effects on cyclooxygenase, 27,28) rat liver mitochondrial ATPase activity 29) and dihydroxyphenylalanine (DOPA) oxidase activity.27) It has also been revealed that oxyresveratro...

Resveratrol: a review of plant sources, synthesis, stability, modification and food application

“…discovered that the method provides a sustainable yield of the final product . Other methods have also been applied …”

Application of aluminum triiodide in organic synthesis

“…The transformations were complete after 3 hours of refluxing in acetonitrile, and afforded polyphenols (56a~56d) in 68~83% yields. [41][42][43] Surprisingly, E-stilbenes were obtained after treatment of Z-stilbenes with AlI 3 (Scheme 3E). 44 Conjugation of Z-4-styrylphenolates, a reactive species derived from 4-methoxystilbenes, may account for the E/Z stereoisomerization.…”

Therapeutic Role of Resveratrol and Piceatannol in Disease Prevention

“…They both can be synthesized by using Perkin's approach, using 3,5-dihydoxyacetophenone as a starting material [45]. They share almost same biological activities such as antioxidant, anti-inflammatory, anticancer and antileukaemic activities (Table 1) [6].…”