Polyketides anthrones

Figure 7.4 Structures of the polyacetylenes, falcarinol (10), and the tricyclic polyketide, anthrone (11).

Aloe (Aloe arborescens) is a medicinal plant rich in aromatic polyketides such as pharmaceutically important aloenin (a hexaketide pyrone), aloesin (a heptaketide chromone), and barbaloin (an octaketide anthrone) (Fig. 4a). Pentaketide chromone synthase (PCS) and octaketide synthase (OKS) are novel plant-specific type III PKSs, which were obtained from the aloe plant by RT-PCR cloning using degenerate oligonucleotide primers based on the conserved sequences of known CHS enzymes [30-33]. The deduced amino acid sequences of PCS and OKS are 91% identical (368/403), and show 50-60% identity to those of other CHS superfamily type III PKSs of plant origin OKS shares 60% identity (240/403) with CHS from... 

Fig. 4 (a) Structures of aromatic polyketides produced by A. arborescens. (b) Proposed enzyme reaction mechanism of PCS, (c) OKS, and (d) PKS3. A hypothetical scheme for the involvement of OKS and as yet unidentified ketoreductase in the biosynthesis of anthrones and anthraquinones is also included... 

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). 

The formation of naphthodianthrones in nature most likely involves emodin anthrone 7 as intermediate which results from cyclisation of a linear polyketide. The latter is formed by condensation of eight acetyl CoA units. Emodin anthrone 7 is then dimerised to penicilliopsin 8 which undergoes oxidation to protohypericin 3, the direct precursor of hypericin 1 [17]-... 

Anthrones e.g., emodin anthrone (12) are probable intermediates in the biosynthesis of anthraquinones such as emodin from polyketide pathways (Fig. 6.22) and occur widely in nature. The position para to the carbonyl oxygen of the center (B) ring is sensitive to oxidation and, in many instances, oxidation products may be the major or only compounds isolated from plants which contain anthraquinones after storage (Leistner, 1985). 

Representatives of this group of polyketides are anthraquinone derivatives and ergochromes. In most of the anthraquinones the nucleus is substituted at C-1 and C-8 with hydroxy groups and may carry an additional hydroxy group at C-3 and a one-carbon side chain at C-6 (Table 34). Anthraquinones are easily reduced to anthrones/anthranols in a reversible reaction ... 

Emodins with both aromatic rings hydroxylated are synthesised exclusively by the polyketide pathway as octaketides. Biosynthesis of bianthrones and other condensed emodin derivatives occurs by one-electron oxidation of anthrone derivatives (anthranols) to radicals, which are joined to form bianthrones. 

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