Acetate-malonate pathway

A quinone methide moiety is present in the dihydropyrans citrinin (695) and pulvilloric acid (696), both of which are derived by the acetate-malonate pathway. 

There are diffent pathways by which all phenolic compounds are synthesized [6,7]. The shikimate/arogenate pathway leads, through phenylalanine, to the majority of plant phenolics, and therefore we shall centre the present revision on the detailed description of this pathway. The acetate/malonate pathway leads to some plant quinones but also to various side-chain-elongated phenylpropanoids (e.g. the group of flavonoids). Finally, the acetate/mevalonate pathway leads by dehydrogenation reactions to some aromatic terpenoids. 

The so-called acetate-malonate pathway leads to three different kinds of natiu al products depending on the detailed pathway followed. Fatty acids result from a reductive pathway to be described here, but acetate and malonate are also precursors for the isoprenoids (terpenes and sterols) produced via mevalonic acid (Ce) and... 

Previous researchers have suggested [6,8] that benzophenones are biosynthesized by condensation of metabolites from the shikimate pathway, forming the A-ring, and the acetate-malonate pathway, creating the B-ring. This produces the basic 13-carbon benzophenone skeleton, Fig. (1). Support for this biosynthetic pathway includes the isolation of benzophenone synthase from Centaurium erythraea [9] and research by Atkinson etal. [10] who examined benzophenones as intermediates in the synthesis of xanthones. (Xanthone biosynthesis is reviewed by... 

Tannins are naturally occurring water-soluble polyphenolic compoimds, and it has been reported that they show their anti-HIV activity by inhibiting polymerase and ribonuclease activities of HIV-1 RT. Phlorotannins are tannin derivatives which contain several phloroglucinol imits linked to each other in different ways and formed by the polymerization of phloroglucinol (1,3,5-trihydroxybenzene) monomer units and biosynthesis through the acetate-malonate pathway. So far, phlorotannins mostly have been isolated from red and brown alga. Numerous bioactivities of phlorotannins have been reported up to date such as antioxidant, antiinflammatory, antibacterial, and anti-MMP activities (Kim et al., 2006 Nagayama et al., 2002). 

Many quinones are derived from acetate-malonate pathways (discussed in Chapter 5), some from shikimate pathways (discussed in Chapter 7), and others are derived by oxidative modification of secondary metabolites from a variety of otiher pathways. Quinones of this last type will be discussed with the compounds to which they are biosyntheti-cally related. 

Anthraquinones derived from acetate-malonate pathways are particularly common in fungi and lichens, but are often found in higher plants as well. Acetate-malonate-de-rived anthraquinones usually can be distinguished by their structures because they possess substituents in both benze-noid rings of the anthraquinone nucleus (also see Chapter 5), although there are some exceptions to this generalization. 

In contrast to its widespread importance in the biosynthesis of secondary metabolites in Lower Fungi 667, 668) the acetate-malonate pathway is only of restricted importance to pigment production in Macromycetes. It is confined to a few basic systems which are categorised below in line with Turner s classification 667) which is based... 

Chrysophanol (XXIII), an anthraquinone isolated from the leaves of Rumex alpinus (Polygonaceae), is also formed from acetate (and presumably therefore derived via the acetate-malonate pathway) (Leistner and Zenk, 1969) and not, as previously considered, from shikimic acid and mevalonate. Only anthraquinones such as alizarin lacking a C-methyl group and not hy-droxylated in ring A are made in this way, despite an apparent similarity in structure thus at least two independent routes also exist for the synthesis of these compounds and reflect the diversity available for the biogenesis of multiringed phenols in plants. 

Benzenoid compounds in plants are synthesized by two main pathways the shikimic acid pathway and the acetate-malonate pathway. In higher plants, a large number of aromatic compounds are derived from phenylalanine, tyrosine, and tryptophan, end-products of the shikimic acid pathway. 

The acetate-malonate pathway of biosynthesis leads, through simple variants, to three major categories of natural products fatty acids by a reductive pathway, isoprenoids via mevalonate, and phenols by cyclisation of polyketides. 

Another major nitrogenous constituent in trees is chlorophyll, but this is essentially absent from woody tissues. The traces of nitrogen-containing compounds in woody tissues often represent intermediary metabolites and translocated forms (Sect. 5.1), and compounds more typical of end-products of metabolism such as the alkaloids (Sect. 5.2). Alkaloids originate from acetate-malonate pathway, the mevalonate pathway, and various amino acid pathways. 

Acetyl CoA is the starting material for the biosynthesis of the fatty acids. It is used for the synthesis of the fatty acids by the acetate-malonate pathway. With the terpenoids we become acquainted with a second, large group of natural products whose biosynthesis starts from acetyl CoA. The terpenoids are furnished via the acetate-mevalonate pathway. 

The acetate-malonate pathway. This is used to synthesize the aromatic ring A of the flavan derivatives. Otherwise this route is more important for microorganisms. 

The synthesis of phenols via the acetate-malonate pathway shows similarities to the synthesis of the fatty acids. In the case of the latter acetyl CoA was the initiator, and here various other acyl CoAs serve this purpose. Three units of malonyl CoA are added to the initiator with accompanying decarboxylation. We may remember that in the case of the fatty acids malonyl CoA was also added with decarboxylation until the final chain length was obtained. In the present case, a polyketoacid is formed which can cyclize in different ways. We are interested here only in the so-called 1-6 C acylation which gives rise to the phenols with the hydroxyl pattern of phloroglucinol. They differ in the nature of their R substituent and, in addition, can be subjected to further modifications. 

Phenol carboxylic acids can also be supplied by the acetate-malonate pathway, at least in microorganisms. In higher plants, however, they are more likely to be derived from cinnamic acids. Let us consider as an example the conversion of /7-coumaric acid into /7-hydroxybenzoic acid and, subsequently, hydroquinone, a sequence of reactions discovered by Zenk. 

Let us summarize biosynthetically the flavan derivatives are hybrid substances. Their A ring is derived from acetate, their B ring and the C atoms 2, 3 and 4 of the heterocycle from phenylpropanes. The 15 C skeleton is probably synthesised from malonyl CoA and cinnamic acid CoA compounds, the reaction sequence being analogous to the acetate-malonate pathway. 

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