Ethyl 4-methoxy-2-methylbenzoate, from

The use of open-chain precursors for obtaining the benzenoid ring in anacardic and orsellinic acids has proved a fruitful approach. Ethyl 2-methoxy-6-methylbenzoate (synthesised through the Michael addition of ethyl acetoacetate virith but-2-en-al, followed by cyclisation and aromatisation), has been alkylated in an aprotic solvent after formation of the carbanion with lithium di-isopropylamide (refs. 113,114) to give the anacardic after hydrolysis and demethylation (a). In a similar way ethyl 2,4-dimethoxy-6-methylbenzoate (ethyl orsellinate), (formed from ethyl acetoacetate and ethyl crotonate followed by cyclisation aromatisation and methylation (ref. 115)), has been alkylated (ref. 116, 117). In this way the C.,5 orsellinic acid precursor [R = C14H29 in route (b)] of the component phenols in Anacardium occidentale has been synthesised (ref. 118) and the method indirectly affords another route to the cardol series. 

Subsequently, this approach to the synthesis of C15 phenolic lipids consisted in the route ArCi - ArCis. It has proved generally convenient for the synthesis of the unsaturated anacardic acids. From the methodological view it is also an aspect of the use of acyclic intermediates discussed in the next section since the starting material ethyl 2-methoxy-6-methylbenzoate is prepared from ethyl acetoacetate. 

Alkylation routes have been used for the monoenes in this group. Thus, ethyl 2-methoxy-6-methylbenzoate as the carbanion (formed from lithium di-isopropylamide) has been alkylated with (Z) 1-bromotetradec-7-ene in the presence of hexamethylphosphoric triamide. Demethylation with lithium t-butytthiolate yielded (15 1)-anacardic acid (ref. 114). A more activated benzyl group having an adjacent sulphur atom was used for a synthesis of the 10(Z)-isomer of ginkgolic acid in the following way (ref. 8). 

As a typical example of tridepside synthesis, the preparation of 5-0-methylhiascic acid (227) is depicted in Scheme 35 122). Persulfate oxidation of ethyl 4-benzyloxy-2-hydroxy-6-methylbenzoate (273) in potassium hydroxide solution gave the corresponding 5-hydroxy derivative (274) from which 2,4-dibenzyloxy-5-methoxy-6-methylbenzoic acid (275) was prepared. Condensation of this acid with benzyl lecanorate (276) gave the... 

Preparation by reaction of ethyl 2-hydroxy-4-methoxy-6-methylbenzoate (m.p. 73-74°) with sodium methyl-sulfinylmethide, itself obtained from DMSO and sodium hydride (85%) [5587]. 

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