The synthesis of kermesic acid and isokermesic acid derivatives and of related dihydroxyanthraquinones

Abstract

Cochinellic anhydride methyl, ethyl and benzyl esters (4-methoxy-4-ethoxy- and 4-benzyloxy-carbonyl-5-hydroxy-3-methylphthalic anhydrides) have been prepared by a single stage Diels–Alder reaction of 2-bromomaleic anhydride with 3-alkoxycarbonyl-2,4-bis(trimethylsilyloxy)penta-1,3-dienes. The corresponding 5-methyl ether ethyl ester has been obtained by a similar addition reaction but with 3-ethoxycarbonyl-2-methoxy-4-trimethylsilyloxypenta-1,3-diene. The synthesis of methyl 6-deoxykermesate by the acylation of 1,4-dimethoxybenzene in the presence of boron trifluoride–diethyl ether with cochinellic anhydride methyl ester is unsuccessful. The preferred route is by the Diels–Alder addition of 3-alkoxycarbonyl-2,4-bis(trimethylsilyloxy)penta-1,3-dienes to naphthazarin (or 2-chloronaphthazarin). Lead tetraacetate oxidation of methyl 6-deoxykermesate affords a bis(quinone), Thiele acetoxylation of which gives after hydrolysis and permethylation, a mixture of derivatives of kermesic and isokermesic acids in equal proportions. The Diels–Alder addition of 3-chlorojuglone and 3-alkoxycarbonyl-2,4-bis(trimethylsilyloxy)penta-1,3-dienes has led to an improved synthesis of aloesaponarin-I (3,8-dihydroxy-2-methoxycarbonyl-1-methylanthra-9,10-quinone), while juglone itself affords an isomer which may be the 3,5-dihydroxy compound.