An Improved Synthesis of Balsaminone A

Abstract

A short and efficient synthesis of balsaminone A, a dinaphthofuran-1,4-dione, is described. The eight-step synthesis features two alternate pathways including a base-induced coupling reaction of 4-methoxy-1-naphthol and 2,3-dichloro-1,4-naphthoquinone, as well as a light-mediated cyclization of 1,1'-binaphthoquinone to afford the dinaphthofurandione core. Subsequent ortho formylation yielded a known precursor to balsaminone A, affording the natural product in 20–27% yield. This represents a moderate increase from the previous synthesis of 7.4% yield.

Key words

balsaminone A - Liebermann coupling - light-mediated cyclization - naphthofurandione - natural products

• References

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• 13 Synthesis of Carbaldehyde 7 DMF (5 mL, 64.85 mmol) in acetonitrile (5 mL) was added dropwise to a solution of oxalyl chloride (5 mL, 58.24 mmol) in acetonitrile (5 mL). The mixture was stirred at –10 °C for 1 h, after which a solution of 5-hydroxy-dinaphthofuran-7,12-dione (9a) (100.6 mg, 0.320 mmol) in acetonitrile (5 mL) and DMF (2 mL) was added, followed by CuI (10 mg, 0.056 mmol). The reaction mixture was stirred to reach r.t. and then heated at reflux overnight. After cooling to r.t., the solvent was removed in vacuo. The remaining residue was dissolved in ethyl acetate (40 mL), washed with water (3 x 10 mL) and brine (2 x 20 mL), and dried with magnesium sulfate. Evaporation of the solvent yielded a brown orange solid (107 mg), which was purified by column chromatography (ethyl acetate/hexane). The desired product was obtained as a pale-orange solid (60.1 mg, 55% yield). Mp 295–298 °C (methylene chloride) (ref.^[8]302 °C); IR: 3678, 1728, 1330 cm^–1; ¹H NMR (MeOH): δ = 14.44 (s, 1 H, H-C=O), 11.17 (s, 1 H, OH), 8.26 (m, 4 H, H-2,3,9,10), 7.43 (m, 4 H, H-1,4,8,11); ¹³C NMR (MeOH): δ = 108.1, 116.9, 121.4, 125.0, 125.9, 126.1, 126.8, 127.7, 128.5, 132.0, 132.1, 133.4, 134.4, 148.0, 153.6, 164.0, 174.4, 180.9, 198.9.