Efficient Access to Chromeno[4,3-b]quinolines Related to Dependensin

Abstract

We report a robust synthesis of novel chromeno[4,3-b]quinoline derivatives structurally similar to the natural product dependensin. The target compounds are accessed through the acid-catalysed condensation of 2-aminoacetophenones or 2-aminochalcones with substituted flavanones, which are in turn obtained from 2-hydroxyacetophenones and benzaldehydes.

Key words

dependensin - chromeno[4,3-b]quinoline - flavanone - acid-catalysed synthesis

• References and Notes

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• 12 Representative Procedure for the Preparation of 12q To a mixture of 5,7,8-trimethoxy-2-phenylchroman-4-one (0.16 mmol, 0.050 g) and 2′-amino-5-chlorobenzophenone (0.16 mmol, 0.037 g) was added T3P^®in 50% EtOAc (0.32 mmol, 0.102 g), and the reaction mixture was stirred at 80 °C for 24 h. Water (25 mL) was added to dissolve the T3P^®and the mixture was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄ filtered, and the solvent removed under reduced pressure. The crude product was recrystallised from MeOH to give a white solid. The white solid was filtered and dried to give pure 12q (51%); mp 222–223 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 8.09 (d, J = 9.0 Hz, 1 H), 7.80 (dd, J = 9.0, 2.4 Hz, 1 H), 7.65–7.61 (m, 1 H), 7.51 (ddt, J = 8.7, 7.5, 1.2 Hz, 2 H), 7.36 (tt, J = 7.6, 0.9 Hz, 1 H), 7.24–7.18 (m, 4 H), 7.10–7.00 (m, 3 H), 6.43 (d, J = 3.4, Hz, 1 H), 6.19–6.15 (m, 1 H), 3.91 (s, 3 H), 3.83 (s, 3 H), 3.53 (s, 3 H).¹³C NMR (151 MHz, DMSO): δ = 155.2, 149.2, 149.0, 146.0, 143.2, 137.6, 133.6, 131.9, 131.3, 130.8, 130.5, 130.3, 129.8, 128.9, 128.6, 128.4, 128.1, 127.4, 126.3, 124.5, 124.3, 124.0, 107.2, 93.1, 75.5, 60.3, 56.5, 55.5. IR (ATR): ν_max = 3035, 2929, 2833, 2340, 2102, 1752, 1571 cm^–1. HRMS (ESI⁺, 47 V): m/z calcd for C₃₁H₂₅ClNO₄ [M + H]: 510.1467; found: 510.1468.
• 13 Representative Procedure for the Preparation of 13l To a mixture of 5,7,8-trimethoxyflavanone (0.16 mmol, 0.050 g) and 2′-amino-4,5,6-trimethoxychalcone (0.16 mmol, 0.050 g) was added T3P^®in 50% EtOAc (0.32 mmol, 0.102 g), and the reaction mixture was stirred at 80 °C for 24 h. Water (25 mL) was added to dissolve the T3P^®and the mixture was extracted with CH₂Cl₂ (3 × 20 mL). The combined organic extracts were washed with brine, dried over Na₂SO₄ filtered, and the solvent removed under reduced pressure. The crude product was recrystallised from MeOH to give a yellow crystalline solid. The yellow solid was filtered and dried to give pure 13l (23%); mp 115–116 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.72 (dd, J = 16.7, 3.2 Hz, 1 H), 7.36–7.33 (m, 2 H), 7.29–7.27 (m, 7 H), 7.18 (dd, J = 5.1, 2.6 Hz, 2 H), 6.70 (d, J = 6.0 Hz, 1 H), 6.40 (d, J = 4.0 Hz, 1 H), 6.11 (d, J = 16.6 Hz, 1 H), 4.01 (s, 3 H), 3.88 (d, J = 14.3 Hz, 6 H), 3.82 (s, 3 H), 3.67 (s, 3 H), 3.49 (s, 3 H).¹³C NMR (151 MHz, DMSO): δ = 155.1, 154.8, 154.6, 148.6, 141.9, 131.9, 131.2, 128.4, 127.9, 127.8, 125.8, 125.6, 125.6, 105.0, 93.0, 75.7, 60.5, 60.4, 60.1, 56.5, 55.6, 55.3. IR (ATR): ν_max = 3749, 2928, 2298, 1913, 1559 cm^–1. HRMS (ESI⁺, 47 V): m/z calcd for C₃₆H₃₄NO₇ [M + H]: 592.2330; found: 592.2333.
• 14 X-ray Crystallography A suitable single-crystal of 13l (CCDC 1548511), obtained from methanol, was selected under a polarizing microscope (Leica M165Z), mounted on a MicroMount (MiTeGen, USA) consisting of a thin polymer tip with a wicking aperture. Crystallographic data excluding structure factors have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication; number CCDC 1548511. A copy of the data can be obtained free of charge from CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK or e-mail: [e-mail].