Orsellinic acids

Urushiol Rhus vernicefera, Rhus toxicodendron 0-orsellinic acid Chaetomium-cochliodes... 

Tetraacetic acid (or a biological equivalent) is suggested as an intermediate in the biosynthesis of phenolic natural products. In the laboratory, it can be readily converted to orsellinic acid. Suggest a mechanism for this reaction under the conditions specified. 

The orsellinic acid derivative lasiodiplodin 84 and its de-O-methyl congener are found, i.a., in the roots of Arnebia euchroma, a plant which is used in traditional Chinese medicine. These compounds elicit diverse biological responses as inhibitors of prostaglandin biosynthesis, cyctotoxic agents, and plant growth regulators. 

Many natural aromatic compounds are produced from the cyclization of poly- -keto chains by enzymic aldol and Claisen reactions. Examples include simple structures like orsellinic acid and phloracetophenone, and more complex highly modified structures of medicinal interest, such as mycophenolic acid, used as an immunosuppressant drug, the antifungal agent griseofulvin, and antibiotics of the tetracycline group, e.g. tetracycline itself. 

The more complex structures are inappropriate for consideration here, but the two compounds orsellinic acid and phloracetophenone exemplify nicely the enolate anion mechanisms we have been considering, as well as the concept of keto-enol tautomerism. 

Ephedra fasciculata Chaetomium globosum orsellinic acid, globosumone A-C 203... 

In 1907, Collie proposed that polymers of ketene (CH2=C=O) might be precursors of such compounds as orsellinic acid, a common constituent of lichens. The hypothesis was modernized in 1953 by Birch and Donovan, who proposed that several molecules of acetyl-CoA are condensed (Eq. 21-19) but without the two reduction steps required in biosynthesis of fatty acids (Fig. 17-12).329 As we now know they were correct in assuming that the condensation occurs via malonyl-CoA and an acyl carrier group of an enzyme. The resulting p-polyketone can react in various ways to give the large group of compounds known as polyketides. 

Figure 21-9 Postulated origin of orsellinic acid and other polyketides.

Penicillic acid (Figure 3.45), another micro-bially produced food contaminant with carcinogenic properties, is synthesized by cultures of Penicillium cyclopium and P. baarnense, and also features oxidative ring fission of an aromatic compound. This time orsellinic acid (Figure 3.25) is a precursor, and ring fission appears to proceed via a quinone, which is the result of decarboxylation, oxidation, and methylation reactions. Figure 3.45 also represents an over-simplistic rationalization of the ring fission process. 

Merely by writing ketones instead of phenols and doing one disconnection corresponding to a simple carbonyl condensation, we have reached a possible starting material which is a typical acyl polymalonate product without any reductions. This is what polyketides are. The fatty acids are assembled with full reduction at each stage. Polyketides are assembled from the same process but without full reduction indeed, as the name polyketide suggests, many are made without any reduction at all. This is the biosynthesis of orsellinic acid. 

This route has been demonstrated by feeding 13C-labelled malonyl CoA to a microorganism. The orsellinic acid produced has three 13C atoms only, seen by an M + 3 peak in the mass spectrum. The location of the labels can be proved by NMR, The starter unit, acetate, is not labelled. 

As the polyketide chain is built up, any of the reductions or eliminations from fatty acid biosynthesis can occur at any stage. The simple metabolite 6-methyl salicylic acid (6-MSAJ is made in the microorganism Penicillium patulum, and it could come from the same intermediate as orsellinic acid with one reduction,... 

Penicillic acid (82 in Figure 17) is a toxic compound produced by many Penicillum and some Aspergillus species.166 It is biosynthesized from orsellinic acid through the pathway shown in Figure 17.167 A candidate of a gene encoding a PKS for penicillic acid biosynthesis was obtained from A. ochraceus 6t... 

Polyketides. These pyranones combine with carbanions obtained from orsellinic acid derivatives to afford polyketide-type compounds. ... 

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