Polyketide aromatic compounds synthesis

In nature, the intramolecular condensation of a 1,3-dicarbonyl moiety with a keto group in polyketides is an important step in the biosynthesis of aromatic compounds. Biomimetic transformations of this type have been intensively investigated by Harris. (For a discussion, see Chapter 1.5, this volume.) In the following, the synthesis of some natural products and biologically active compounds using the Knoevenagel reaction will be described. 

These are called acetogenins (or sometimes polyketides). Many of these compounds are aromatic, and their pathway of formation is the principal means of synthesis of the benzene ring in nature. Not all are lipids, because partial reduction often leaves oxygen-containing groups, which render the product soluble in water. 

Three different metabolic pathways are known to be involved in the synthesis of different classes of phenolic compounds, namely, (1) (Ce — C3) phenylpropanoid derivatives produced by the shikimate/chorismate pathway (2) side chain elongated phenylpropanoids, flavonoids (Ce - C3 - Cg), and few quinones synthesized by the acetate/malOTiate or polyketide pathway and (3) the aromatic terpenoids synthesized throu the acetate/mevalonate pathway. 

Hay and Harris 153,157) have reported a biogenetic-type synthesis of lichexanthone (Scheme 14). To circumvent problems arising from numerous cyclisation pathways of a long polyketide chain these workers chose a starting compound with a pre-formed aromatic ring (132). Claisen condensation of the polyketide side chain of (132) in aqueous potassium hydroxide yielded a mixture of the benzophenone (133) and 3-0-methylnorlichexanthone (134). The benzophenone (133) could be converted into (134) by treatment with methanolic potassium hydroxide. Subsequent O-methylation of (134) with diazomethane yielded lichexanthone (135). 

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