Stilbene family

Resveratrol is a member of the stilbene family, a group of compounds which consist of two aromatic rings joined by a methylene bridge. 3,4, 5-trihydrox-ystilbene is the IUPAC (International Union of Pure and Applied Chemistry) nomenclature for resveratrol but is also known as 3,4, 5-stilbenetriol, and it has... 

The triphenylethylene antiestrogens (Fig. 46.9) are structurally related to the stilbene family of estrogens and exhibit high affinity for the ER. They prevent translocation of the estrogen-receptor complex into the nucleus of target cells and interfere with the binding of the receptor-hormone complex to the acceptor site of the chromatin (29,30). 

Members of the stilbene family which have the C6-C2-C6 structure (Table 1.1), like flavon-oids, are polyphenolic compounds. Stilbenes are phytoalexins, compounds produced by plants in response to attack by fungal, bacterial and viral pathogens. Resveratrol is the most common stilbene. It occurs as both the cts and the trans isomers and is present in plant tissues primarily as fra s-resveratrol-3-0-glucoside which is known as piceid and polydatin (Figure 1.14). A family of resveratrol polymers, viniferins, also exists. 

Apart from monooxygenases, other enzymes concerned wih xenobiotic metabolism may also be induced. Some examples are given in Table 2.5. Induction of glucuronyl transferases is a common response and is associated with phenobarbital-type induction of CYP family 2. Glutathione transferase induction is also associated with this. A variety of compounds, including epoxides such as stilbene oxide and... 

For example, stilbene oxygenases, which cleave the interphenyl a,P-double bond of stilbene derivatives, are known to be members of the CCO family of enzymes that act on substrates other than... 

Chalcone Synthase / Stilbene Synthase Family of Plant Polyketide Synthases. 199... 

Recently, a new polyketide biosynthetic pathway in bacteria that parallels the well studied plant PKSs has been discovered that can assemble small aromatic metabolites.8,9 These type III PKSs10 are members of the chalcone synthase (CHS) and stilbene synthase (STS) family of PKSs previously thought to be restricted to plants.11 The best studied type III PKS is CHS. Physiologically, CHS catalyzes the biosynthesis of 4,2, 4, 6 -tetrahydroxychalcone (chalcone). Moreover, in some organisms CHS works in concert with chalcone reductase (CHR) to produce 4,2 ,4 -trihydroxychalcone (deoxychalcone) (Fig. 12.1). Both natural products constitute plant secondary metabolites that are used as precursors for the biosynthesis of anthocyanin pigments, anti-microbial phytoalexins, and chemical inducers of Rhizobium nodulation genes.12... 

CHALCONE SYNTHASE / STILBENE SYNTHASE FAMILY OF PLANT POLYKETIDE SYNTHASES... 

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). 

To resolve the issue of cyclization specificity, the x-ray crystal structure of the stilbene synthase from pine was determined to atomic resolution. This information allowed the mutagenic conversion of alfalfa CHS to a functional STS, and crystal structures of this engineered STS were solved, in the apo form and with resveratrol bound in the active site (Austin and Noel, unpublished). These experiments support a mechanistic proposal, which prompted further mutagenic and modeling experiments. This work has allowed the elucidation of the structural and mechanistic basis for cyclization specificity (aldol versus Claisen condensation) in the CHS family of type III PKSs. 

SCHRODER, J., The chalcone/stilbene synthase-type family of condensing enzymes. In Comprehensive Natural Products Chemistry, vol. 1, Polyketides and Other Secondary Metabolites Including Fatty Acids and Their Derivatives (U. Sankawa ed.), Elsevier, Amersterdam, 1999, pp. 749-771. 

No. Flavanone Formula Flavanone-stilbenes (Figure 15.7) Mr Plant Source Family Organ Ref. 

A very large number of substituted phenanthrenes have been made from stilbenes by this photocydization method, as have more complex polycyclic aromatic compounds by related reactions involving a single cydizatlon (e.g. 3.64 for chrysenes) or two, or more, successive cydizations le.g. 3.65). The reaction can be nicely adapted to provide a route from 1-benzylidenetetra-hydroisoquinolines to alkaloids of the aporphine family (e.g. 3.66). 

Schroder J (1999) The chalcone/stilbene-synthase family of condensing enzymes. In Sankawa U (ed) Comprehensive natural products chemistry, vol 1. Pergamon, Oxford, pp 749-771... 

Mallory, F.B., Butler, K.E., and Evans, A.C. (1996) Phenacenes a family of graphite ribbons. 1. Syntheses of some [7]phena-cenes by stilbene-like photocydization. Tetrahedron Letters, 37, 7173-7176. 

Figure 8 Polyketides of the chalcone super family of chalcone and stilbene (The illustrated [ 2]acetate labeling is extrapolated from related incorporation studies)...

Diols and derivatives. In the Combretastatins A family, the corresponding (E) stilbenes and bibenzyls, e.g. Combretastatin B-1 and analogues, which contain an -hybridized freely rotating ethane bridge, exhibit a decrease in antineoplastic activity when compared to the corresponding (Z)-stilbenes. To explore the possible conversion of the inactive ( )-isomer of Combretastatins A-1 and A-4 into a more active derivatives, a series of compounds was synthesized where the (E)-olefin unit was replaced by a freely rotating 5/73-hybridized chiral C-2 unit [35, 36]. 

Further series of non-centrosymmetric conjugated molecules are currently under investigation [38]. In keeping with the known failure [36] of the two-state model for the family of stilbenes, Ar -CH=CH-Ar, our r ults indicate that such systems do not follow the same correlation observ i for the benzene derivatives. 

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