The chemistry of fungi. Part 76. The synthesis and transformations of three stereoisomeric 2-(2,6-dimethoxybenzoyl)-3-methoxycarbonyl-7-oxabicyclo[2,2,1]heptanes

Abstract

Condensation of 1-lithio-2,6-dimethoxybenzene with the anhydride (10) of 7-oxabicyclo[2.2.1]heptane-2β,3β-dicarboxylic acid and subsequent esterification of the product gave 2β-(2,6-dimethoxybenzoyl)-3β-methoxycarbonyl-7-oxabicyclo[2.2.1]heptane (8; R¹= H, R²= Me). The isomeric 2α-(2,6-dimethoxybenzoyl)-3amethoxycarbonyl-7-oxabicyclo[2.2.1]heptane (11; R = Me) was prepared similarly using the anhydride (9) from 7-oxabicyclo[2.2.1]heptane-2α,3α-dicarboxylic acid. Epimerisation of (11; R = Me) or of (8; R¹ H, R²= Me) gave 2α-(2,6-dimethoxybenzoyl)-3β-methoxycarbonyl-7-oxabicyclo[2.2.1]heptane (12).

Treatment with boron trichloride of (11; R = Me) gave 1 α-chloro-4β-hydroxy-2α-(2-hydroxy-6-methoxybenzoyl)-3α-methoxycarbonylcyclohexane (13; R = H) and 1,7α-dihydroxy-8β-methoxycarbonyl-5aα,5,6,7,8,8aα-hexahydroxanthone (23; R = H); similarly (8; R¹= H, R²= Me) gave 4β-hydroxy-2β-(2-hydroxy-6-methoxybenzoyl)cyclohexane-1β,3β-carbolactone (24; R = H) and 1,7α-dihydroxy-8α-methoxycarbonyl-5aα,5,6,7,8,8aβ-hexahydroxanthone (25; R = H). The third isomer (12) formed 4α-chloro-1β-hydroxy-2α-(2-hydroxy-6-methoxybenzoyl)-3β-methoxycarbonylcyclohexane (31; R = H) together with 1,7α-dihydroxy-8αmethoxycarbonyl-5aα,5,6,7,8,8aα-hexahydroxanthone (32; R = H).

Hydrogenolysis of (1; R¹= R²= Me) or treatment of (11; R = Me) with acid yielded 2-(2,6-dimethoxybenzoyl)-4β-hydroxy-3α-methoxycarbonylcyclohexene (15; R = H); the corresponding acetate (15; R = Ac) was hydroxylated to form 4β-acetoxy-2α-(2,6-dimethoxybenzoyl)-1β,2β-dihydroxy-3α-methoxycarbonylcyclohexane (18) as the major product. The stereoisomeric cyclohexene (34; R = H) was similarly obtained.

Bromination of the ketone (11; R = Me) gave the α-bromjketone (33) : similarly the α-bromoketone (8; R¹= Br, R²= Me) was obtained from (8; R¹= H, R²= Me) and (12). Dehydrobromination of each of these bromoketones formed 2-(2,6-dimethoxybenzoyl)-3-methoxycarbonyl-7-oxabicyclo[2.2.1]hept-2-ene (1; R¹= R²= Me).

Various further transformations of these products are described.