Synthetic Studies towards Stachybotrin C

Abstract

The preparation of racemic des-hydroxy stachybotrin C is described. Different approaches have been studied. Observations made in the course of the synthesis show the efficiency of the intermolecular cyclization between the diethyl acetal 19 and phenol 12 leading to the benzopyran moiety 17.

Key words

natural products - pyrano-isoindolinone - spiro compounds - cyclization

• References and Notes

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• 11 To a solution of 12 (500 mg, 1.34 mmol, 1.0 equiv) in anhydrous o-xylene (8 mL), 19 (790 mg, 2.68 mmol, 2.0 equiv) and 3-picoline (33 μL, 0.34 mmol, 0.25 equiv) were added. The reaction mixture was heated to reflux for 48 h, then the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (CH₂Cl₂–EtOAc, 9:1→4:1) to afford 17 (775 mg, 75%) as a brown oil. ¹H NMR (500 MHz, CDCl₃): δ = 1.40 (s, 3 H), 1.56 (s, 3 H), 1.59 (s, 3 H), 1.66–1.76 (m, 5 H), 1.92–1.97 (m, 2 H), 2.01–2.15 (m, 4 H), 2.92 (t, J = 7.5 Hz, 2 H), 3.47 (s, 3 H), 3.48 (s, 3 H), 3.74–3.84 (m, 2 H), 4.16 (s, 2 H), 5.05–5.14 (m, 2 H), 5.15 (s, 2 H), 5.22 (s, 2 H), 5.61 (d, J = 10.2 Hz, 1 H), 6.76 (d, J = 10.2 Hz, 1 H), 6.96 (d, J = 8.7 Hz, 2 H), 7.07 (s, 1 H), 7.16 (d, J = 8.7 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃): δ = 15.9, 17.7, 22.5, 25.7, 26.6, 34.0, 39.6, 41.2, 44.3, 47.7, 55.9, 56.3, 78.9, 94.5, 95.0, 101.2, 113.6, 116.4, 117.5, 121.4, 123.6, 124.2, 129.4, 129.7, 131.4, 132.1, 133.9, 135.5, 148.2, 153.2, 155.9, 168.3. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₅H₄₅NO₆Na: 598.3139; found: 598.3139.
• 12 To a solution of 17 (200 mg, 0.35 mmol, 1.0 equiv) in anhydrous MeOH (4 mL) was added at 0 °C, acetyl chloride (100 μL, 1.39 mmol, 4.0 equiv). The solution was stirred at room temperature for 20 h then concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (PE–EtOAc, 1:1) to afford 20 (140 mg, 82%) as a pale-yellow oil. ¹H NMR (500 MHz, CDCl₃): δ = 1.37 (s, 3 H), 1.56 (s, 3 H), 1.58 (s, 3 H), 1.66 (s, 3 H), 1.66–1.76 (m, 2 H), 1.92–1.97 (m, 2 H), 2.01–2.15 (m, 4 H), 2.85 (t, J = 7.5 Hz, 2 H), 3.70–3.84 (m, 2 H), 4.17 (s, 2 H), 5.05–5.14 (m, 2 H), 5.55 (d, J = 10.2 Hz, 1 H), 6.76–6.79 (m, 3 H), 6.96–7.01 (m, 3 H), 7.46 (br s, 1 H), 8.40 (br s, 1 H). ¹³C NMR (125 MHz, CDCl₃): δ = 15.9, 17.7, 22.5, 25.7, 26.6, 26.6, 33.8, 39.6, 41.2, 44.4, 47.9, 79.0, 102.4, 112.2, 115.6, 117.5, 119.6, 123.7, 124.2, 129.0, 129.7, 130.2, 131.4, 133.2, 135.6, 148.4, 152.7, 154.6, 169.0. HRMS (ESI): m/z [M + Na]⁺ calcd for C₃₁H₃₇NO₄Na: 510.2620; found: 510.2621.