Naturally occurring dibenzofurans. Part 2. The synthesis of schizopeltic acid

Abstract

The structure of schizopeltic acid as 1,7-dimethoxy-8-methoxycarbonyl 3,9-dimethyldibenzofuran-4-carboxylic acid (1 ) has been confirmed by rational synthesis. 6-Methoxy-4-methylbenzofuran-2-carbaldehyde (1 0), available from 3,5-dimethoxytoluene (4) in six steps, was converted into methyl 1 -acetoxy-7-methoxy-9-methyldibenzofuran-3-carboxylate (1 2) by Wittig reaction with 2-carboxy-l-methoxycarbonylethyltriphenylphosphorane and subsequent ring-closure of the resultant (€)-3-methoxycarbony1-4-(6-methoxy-4-methylbenzofuran-2-y1)but-3-enoic acid (1 1 ) with acetic anhydride. Reduction of compound (1 2) gave 7-methoxy-3,9-dimethyldibenzofuran-1 -01 (1 4) which was converted into schizopeltic acid (1 ) by sequential formylations and oxidations.

A Biomimetic Synthesis Elucidates the Origin of Preuisolactone A

“…To provide support for this hypothesis, we decided to probe it with a biomimetic synthesis (Scheme 2). It started with the known 29 resorcinol ether 11, which underwent Dakinoxidation to afford the catechol 1. Incubation of 1 with the known 30 symmetric pyrogallol 2 in the presence of potassium ferricyanide triggered the first phase of the cascade and gave a mixture of interconverting isomers that presumably contain the diosphenol 7, its 1,2-diketo form, and the acetal 12.…”

Ethynylbenzenoid metabolites of Antrodia camphorata: synthesis and inhibition of TNF expression

“…Chang, Wu and co-workers used a similar approach in their synthesis of antrocamphin A, in which they prepared 5 by the silver trifluoroacetate-mediated iodination of 2,3,5-trimethoxytoluene (10) (see Scheme 2 for structure), in turn derived from o-vanillin in four steps and 46% overall yield. 5 Our approach began with Vilsmeier-Haack formylation of 3,5-dimethoxytoluene (6), 6 followed by Baeyer-Villiger oxidation 7 of the resultant benzaldehyde 7 (Scheme 2). Initially the latter reaction provided the desired phenol 8 contaminated by the corresponding quinone 9, resulting from over oxidation.…”

“…2,4-Dimethoxy-6-methylbenzaldehyde (7) 6 POCl 3 (14.5 mL, 0.156 mol) was added dropwise to a solution of 3,5-dimethoxytoluene (19 g, 0.12 mol) in DMF (100 mL) at 0 °C. The reaction was allowed to warm to room temperature over 24 h before being poured slowly into cold H 2 O (100 mL).…”

“…= 64-65 °C [lit. 6 64-65 °C]. 1 H NMR (400 MHz) δ 10.48 (s, 1H, CHO), 6.32 (s, 2H, 2 × ArH), 3.87 (s, 3H, OMe), 3.85 (s, 3H, OMe), 2.58 (s, 3H, Me).…”