Orsellinic acid derivatives

In all instances these mononuclear compounds were accompanied by the structurally related depsides and tridepsides. 

Evernia prunastri has proved to be a particularly rich source of lichen compounds and extraction and g.c. — m.s. studies have revealed the presence of orcinol (99) 268, 269), 3-methoxy-5-methylphenol (100) 144), 3,5-dimethoxytoluene (101) 144), 2-chloro-3,5-dimethoxytoluene (102) 144), phenol 144), thymol 144), 2-chloro-3-methoxy-5-methylphenol (103) 144), methyl salicylate 144), methyl 4-O-methylorsellinate (90) 268, 269), and methyl (3-orcinolcarboxylate (104) (255). Rhizonic acid (105) has been isolated from Parmelia subnuda 215). 

A mononuclear phenolic compound tentatively assigned the structure of ethyl 2-hydroxy-4-methoxy-6-pentylbenzoate (106) has been isolated by SoLBERG from Icmadophila ericetorum 305) but the possibility that this compound may be an artefact of the ethanolic work-up procedure is not discussed. 

Orsellinic acid and its homologues form the most common mononuclear structural units of polyketide-derived lichen metabolites, but compounds derived from phloroacetophenone (107) (through an alternative cyclisation 

In both lichens the ketones co-occur with atranorin (110) and it has been pointed out by Culberson, Culberson and Johnson (78) that from the data available, (108) could not be distinguished from methyl P-orsellinate (111), a possible artefact of atranorin. 

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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. 

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

Griffin DA, Staunton J (1975) A novel biogenetic-type synthesis of an orsellinic acid derivative. Chem Commun 675-676... 

Route A involves the condensation of appropriately substituted phloro-glucinol derivatives with substituted orsellinic acid derivatives in the presence of anhydrous zinc chloride and phosphorus oxychloride. The analogous condensation in the presence of trifluoroacetic anhydride yielded the xanthone (150) (C-acylated product) as a minor byproduct together with the major aryl ester (151) (0-acylated product). However trifluoroacetic anhydride has become the reagent of choice (route B) since the use of 0-methyl and 0-benzyl protecting groups has enabled good yields of the xanthones to be obtained. 

Cell-free systems capable of in vitro synthesis of 6-methylsalicylic acid (6-MS A) and a related tetraketide, orsellinic acid, were developed long before the advent of recombinant DNA technologies in the field of natural product biosynthesis [113-115] (Fig. 5). Since then, the biosynthetic mechanisms and molecular recognition features of 6-methylsalicylic acid synthase (6-MSAS) have been extensively studied. 6-MSAS initiates synthesis with an acetyl group derived from acetyl Co A, extends the polyketide chain to a tetraketide via three decar-boxylative condensations of malonyl CoA-derived extender units, and uses NADPH to specifically reduce one of resulting carbonyls to a hydroxyl group. In its natural producer, Penicillium patulum, the product, 6-MSA is subsequently glycosylated to form the antibiotic patulin [116]. 

The facile decarboxylation of resorcinol carboxylic acids and notably of orsellinic acids in alkaline solution poses a problem during their syntheses in high yield. For this reason the synthesis of alkoxycarbonyl derivatives is usually adopted followed by acidic hydrolysis. The removal of the protective acetyl groups in the compound shown was effected preferentially without hydrolysis of the ester group. Methyl 2,6-diacetoxybenzoate in toluene saturated with water when add to a catalyst (prepared from 4-toluenesulphonic acid monohydrate and silica gel) and stirr at 86°C during 6 hours, afford methyl... 

A closely related methodology (route c) involves the dianion from a diketone (R = Me) with the anion of dimethyl malonate (R = Me) (ref.25). The bis-trimethylsilyl ether from methyl acetoacetate has been interacted with the ketalised acid chloride shown (R = CgH ) to furnish the methoxy carbonyl derivative of olivetol (route d) (ref.26). It was also found that pentane-2,4-dione with dimethyl malonate in the presence of sodium hydride afforded methyl orsellinate (ref.26). In a biomimetic approach (route e) a tetraketone has been enzymically cyclised to give the corresponding orsellinic acid (R=H, R = alkyl) (ref. 27). 

C13 Orsellinic acid eg. l,3-Dihydroxy 5-(2-acetoxy-12-hydro qr- 42 derivs) (Table 13.1) tridecylbenzene... 

Reaction with enol ethers of ethyl acetoacetate. Reaction of the ethyl enol ether of ethyl acetoacetate (1) with TiCla gives the derivative (2) of p-orsellinic acid the phenyl enol ether (3) under the same conditions is converted into the derivative (4) of o-orselUnic acid. ... 

The C-methyl group attached to the ring in typical phenols (formed by an aldol condensation step), such as 6-methylsalicyclic acid (I), orsellinic acid (V), and altemariol (III), is derived from the acetyl-CoA primer. In other representative compounds, for example acetyl phloroglucinol (VI), an acetyl residue remains external to the ring as a result of cyclization by a C-acyla-tion process (Birch and Donovan, 1953). 

This view was confirmed more directly when 5-methylorcylaldehyde (XXIV) but not orcylaldehyde was converted to substituted toluquinols and gliorosein (XXV) by Gliocladium roseum, implying that the C-methyltrans-ferase concerned could not accept the aromatic orcylaldehyde (Steward and Packter, 1968). In addition, whereas acetate (Yamazaki et al., 1%5) and or-sellinic acid (Yamazaki and Shibata, 1966) were both incorporated into the depside lecanoric acid (XXVI) (derived by esterification of two molecules of orsellinic acid) in the lichen Parmelia tinctorum, orsellinic acid was not converted to the related atranorin (XXVIl) (Yamazaki and Shibata, 1966) this... 

Examples of P. are Tetra clines (see), Griseofulvin (see), Macrolide antibotics (see), Cydoheximide (see), and various fungal products such as orsellinic acid, 6-methylsalicylic acid and cyclopaldic add. [ The Biosynthesis of Acetate-Derived Phenols (Polyketides) by N.M.Packter pp. 535-570, in The Biochemistry of Plants, V6I4, 1980 (Edit. P.K. Stumpf), Academic Press S.Sahpaz et al. Phytochemistry 42 (1996) 103-107]... 

Deriv Orsellinic acid, mp 197-198 °C (acetone-HjO), from etbyl orsellinate by hydrolysis with NaOH-HjO at room temperature StL Roccella fuciformis (L.) DC. 

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