Polyketides aromatic natural products

Aromatic natural products of polyketide origin are less prevalent in plants compared with microorganisms. The majority of the plant constituents that contain aromatic stmctures are known to arise from the shikimate pathway (see below). Unlike those derived from the shikimate pathway, aromatic products of the polyketide pathway invariably contain a meta oxygenation pattern because of their origin from the cyclization of polyketides. Phenolic compounds such as chrysophanol-anthrone (Bl), and emodin-anthrone (B2), and the anthraquinones, aloe-emodin (B3) and emodin (B4) (Fig. 2), are products of the polyketide pathway and are found to occur in some plants of the genera Cassia (Leguminosae) (21), Rhamnus (Rhamnaceae) (22), and Aloe (Liliaceae) (23). The dimer of emodin-anthrone (B2), namely hypericin, (B5) is a constituent of the antidepressant herbal supplement, St. John s wort (Hypericumperforatum, Hy-pericaceae) (24). 

CgHgOi, Mr 168.15, needles, mp. 176 °C (anhydrous), 186-189 °C (monohydrate), soluble in water and alcohol. The phenolcarboxylic acid O. represents an important intermediate in the biosynthesis of aromatic natural products from polyketides. 

T. M. Harris and C. M. Harris, Synthesis of Polyketide-type Aromatic Natural Products by Biogenetically Modelled Routes , Tetrahedron, 1977, 33, 2159. 

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... 

McDaniel R, Ebert-Khosla S, Hopwood DA, Khosla C. (1995). Rational design of aromatic polyketide natural products by recombinant assembiy of enzymatic subunits. Nature, 375,549-54. 

Many of the unusual compounds that indicate the exciting chemistry to be discovered in marine natural products are polyketides. Polyketides are a family of structurally complex natural products that include a number of important pharmaceuticals. They are produced primarily by microorganisms through a specialized metabolism that is a variation of fatty acid biosynthesis [430]. Polyketides fall into two structural classes aromatic and complex. Polyketides are formed by enzyme complexes... 

Polyketides.1 Polyketides are useful as precursors to acetate-derived natural products, but they are unstable owing to a marked tendency to undergo internal condensation. A new synthesis involves ozonolysis of products of Birch reduction. An example is the synthesis of the polyketide 3 from the aromatic system 1. 

Collie s hypothesis that aromatic compounds are made biologically from ethanoic acid was greatly expanded by A. J. Birch to include an extraordinary number of diverse compounds. The generic name acetogenin has been suggested as a convenient classification for ethanoate (acetate)-derived natural products, but the name polyketides also is used. Naturally occurring aromatic compounds and quinones are largely made in this way. An example is 2-hydroxy-6-methylbenzoic acid formed as a metabolite of the mold Penicillium urticae ... 

The polyketide-derived aryl C-glycoside natural products have a variety of interesting biological activities, most notably antitumor activity (7). The defining feature of members of this class is a carbon-carbon bond linking a polycyclic aromatic "aglycone" and the anomeric carbon of a carbohydrate (Figure 1). 

Similar to other natural products, phytotoxins are classified on the basis of their structural types considering their biosynthetic pathways. Among various phytotoxin families, polyketides including aromatic and reduced polyketides, peptides including diketopiperazines, and terpenes are most frequently described in the literature. In this section, representative phytotoxins that are well-characterized biosynthetically and physiologically will be introduced. 

Chalcone synthase (CHS), the first plant natural product polyketide synthase (PKS) to be characterized at the molecular level (39), catalyzes the condensation of 4-coumaroyl-CoA with three molecules of malonyl-CoA to afford naringenin chalcone, a precursor of the major classes of plant flavonoids. The cloning of a novel type III pentaketide chromone synthase (PCS) from aloe (Aloe arborescens, Liliaceae) rich in aromatic polyketides, especially quinones such as aloe-emodin and emodin, resulted in... 

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