Total Syntheses of Atrovenetin and Atrovenetinone: A Naphthalene-Annulation Approach to a Discoid Tricycle Using Allenic Acid

Abstract

A total synthesis of atrovenetin has been achieved. The discoid tricyclic motif was constructed by a novel three-carbon annulation of naphthalene derivative and allenic acid under acidic conditions. An effective protocol for the conversion of atrovenetin into atrovenetinone has been established.

Key words

allenic acid - discoid - heptaketide - phenalenone - total synthesis

• References and Notes

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Interestingly, the polarity of tricycle 14 was higher than that of carboxylic acid 15 (hexane–EtOAc, 70:30; 14: R_f = 0.07, 15: R_f = 0.31). For high polarity of phenalenone, see:
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• 24 Experimental Procedure for Annulation of a Naphthalene Derivative with Allenic Acid To a solution of naphthalene 4 (259 mg, 0.780 mmol) and allenic acid 10 (85.2 mg, 1.01 mmol) in DCE (7.8 mL) was added TMSOTf (425 μL, 2.34 mmol) at 0 °C. After stirring for 6 h, the resulting solution was allowed to warm to r.t. After additional stirring for 12 h, the reaction mixture was quenched by adding sat. aq NaHCO₃. The crude products were extracted with CH₂Cl₂ (3×), and combined organic extracts were washed with brine, dried (Na₂SO₄), and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel; CHCl₃–MeOH, 99:1 → 98:2) to afford tetracycle 21 (264 mg, 85%) as a yellow green crystal. Compound 21: R_f = 0.24 (hexane–EtOAc, 50:50); mp 158–159 °C (EtOAc–hexane). ¹H NMR (600 MHz, CDCl₃): δ = 1.31 (s, 3 H), 1.44 (d, J = 6.0 Hz, 3 H), 1.56 (s, 3 H), 2.59 (s, 3 H), 3.93 (s, 3 H), 4.01 (s, 3 H), 4.02 (s, 3 H), 4.06 (s, 3 H), 4.52 (q, J = 6.0 Hz, 1 H), 6.46 (s, 1 H). ¹³C NMR (150 MHz, CDCl₃): δ = 14.5, 22.0, 24.2, 25.8, 44.0, 61.5, 61.9, 62.8, 63.9, 89.8, 106.5, 115.3, 119.0, 128.3, 123.0, 130.2, 144.6, 147.2, 154.8, 156.8, 159.8, 161.6, 183.2. IR (ATR): 2960, 2924, 1631, 1616, 1591, 1548, 1394, 1379, 1362, 1326, 1279, 1250, 1201, 1156, 1140, 1106, 1066, 1048, 1028, 997, 982, 973, 939, 883, 841, 798, 702 cm^–1. ESI-HRMS: m/z calcd for C₂₃H₂₇O₆ [M + H]⁺: m/z = 399.1802; found: 399.1816.
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