Convenient syntheses of the naturally occurring benzo[b]xanthen-12-one bikaverin. X-Ray crystallographic confirmation of the product regiochemistry

Abstract

The synthesis of bikaverin (6,11-dihydroxy-3,8-dimethoxy-1-methylbenzo[b]xanthene-7,1 0,12-trione)(1) by two related routes is reported. Key steps include the formation of 1,2,4,5,8-pentamethoxynaphthalene (4) in good yield and its regiospecific acylation at C-6 with 2-benzyloxy-4-methoxy-6-methylbenzoic acid. Different methods are used to convert the derived orsellinylnaphthalene into 2,3-dihydro-5,8-dihydroxy-6,6′-dimethoxy-4′-methylnaphthalene-2-spiro2′-2′H-benzofuran-1,3′,4-trione (23) and the corresponding 5,6,6′,8-tetramethoxy analogue (25). Pyrolysis of these spiro compounds gives high yields of bikaverin from (23) and 6,11 -dihydroxy3,7,8,10-tetramethoxy-1-methylbenzo[b]xanthen-12-one (27) from (25). Compound (27) is readily converted into bikaverin.