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Synlett 2003(12): 1886-1888  
DOI: 10.1055/s-2003-41473
LETTER
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of the Angucylinone Antibiotic (+)-Rubiginone B2 [1]

Aris Kalogerakis, Ulrich Groth*
Fachbereich Chemie, Universität Konstanz, Fach M-720, Universitätsstraße 10, 78457 Konstanz, Germany
Fax: +49(7531)884155; e-Mail: ulrich.groth@uni-konstanz.de;
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Publication History

Received 30 June 2003
Publication Date:
19 September 2003 (online)

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Abstract

A new chiral synthesis of (+)-rubiginone B2 is reported. The intramolecular cobalt-mediated [2+2+2]-cycloaddition of a triyne precursor, synthesized from (+)-citronellal, afforded a chiral anthracene, which led after a two-step oxidation to the angucycli­none antibiotic.

Key words

angucyclinone antibiotics - benz[a]anthraquinones - natural products - catalysis - cobalt - cycloaddition

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Experimental Procedure: A solution of CpCo(CO)2 (25.00 mg, 0.142 mmol, 10 mol%) in 2 mL toluene was added via canula to a solution of triyne 9 (0.58 g, 1.42 mmol) in 120 mL toluene and the mixture was heated to reflux and irradiated with a tungsten-lamp (osram vitalux 300 W) for 4 h. The organic phase was then concentrated in vacuo. Chromatography on silica gel (Et2O-petroleum ether, 1:200) provided anthracene 10 (0.29 g, 1.051 mmol, 74% yield) as a white solid.
Mp 136-138 °C. [α]D 22 +86.43 (c 0.14, CHCl3). Rf = 0.31 (Et2O-petroleum ether, 1:100). IR (CCl4): 2935-2810 [C-H (OCH3)] cm-1. 1H NMR (600 MHz, CDCl3): δ = 1.16 (d, 3 J = 6.6 Hz, 3 H, 3-CH3), 1.58 (m, 1 H, H-2), 2.00 (m, 1 H, H-3), 2.14 (m, 1 H, H-2), 2.60 (dd, 2 J = 16.5 Hz, 3 J =10.5 Hz, 1 H, H-4), 2.95 (dd, 2 J = 16.5 Hz, 3 J = 3.9 Hz, 1 H, H-4), 3.14 (m, 1 H, H-1), 3.40 (d, 2 J = 16.5 Hz, 1 H, H-1), 4.09 (s, 3 H, OCH3), 6.73 (d, J o = 8.0 Hz, 1 H, H-9), 7.18 (d, J o = 8.6 Hz, 1 H, H-5), 7.37 (t, J o = 8.0 Hz, 1 H, H-10), 7.62 (d, J o = 8.0 Hz, 1 H, H-11), 7.82 (d, J o = 8.6 Hz, 1 H, H-6), 8.44 (s, 1 H, H-12), 8.78 (s, 1 H, H-7). 13C NMR (100 MHz, CDCl3): δ = 21.79 (3-CH3), 25.83 (C-1), 28.88 (C-3), 31.35 (C-2), 39.14 (C-4), 55.45 (OCH3), 101.34 (C-9), 120.75 (C-12), 120.83 (C-11), 121.35 (C-7), 125.06 (C-10), 126.58 (C-6), 128.05 (C-5), 124.09, 130.34, 131.42, 132.64, 133.57, 155.38 (Cquart-arom.). EI-MS (70 eV): m/z = 276 (100%, M+), 261 (15%, M+ - CH3), 246 (7%, 261 - CH3), 233 (77%, 261 - C2H4). HRMS: calcd 276.1514 for C20H20O, found 276.1508.

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Experimental Procedure: Anthraquinone 11 (60.00 mg, 0.195 mmol) was dissolved in 5 mL CHCl3 and irradiated with a tungsten-lamp (osram vitalux 300 W) over 18 h. The organic layer was then removed in vacuo. Chromatography on silica gel (petroleum ether-Et2O, 1:2) provided (+)-rubiginone B2 12 (42.00 mg, 0.131 mmol, 67% yield) as a yellow solid.
Mp > 262 °C (dec.). [α]D 25 +71.64 (c 0.275, CHCl3, recrystallized from petroleum ether-CHCl3, 2:1). Rf = 0.14 (Et2O-petroleum ether, 1:4). IR (CCl4): 1673, 1677, 1708 (C=O) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.20 (d, 3 J = 6.4 Hz, 3 H, 3-CH3), 2.45 (m, 1 H, H-3), 2.55 (dd, 2 J = 15.6 Hz, 3 J = 11.0 Hz, 1 H, H-2), 2.67 (dd, 2 J = 16.4 Hz, 3 J = 11.0 Hz, 1 H, H-2), 2.98 (m, 2 H, H-1 and H-4), 4.04 (s, 3 H, OCH3), 7.24 (d, J o = 8.2 Hz, 1 H, H-9), 7.45 (d, J o = 8.0 Hz, 1 H, H-5), 7.65 (t, J o = 8.2 Hz, J o = 7.8 Hz, 1 H, H-10), 7.71 (d, J o = 7.8 Hz, 1 H, H-11), 8.20 (d, J o = 8.0 Hz, 1 H, H-6). 13C NMR (150 MHz, CDCl3): δ = 21.43 (3-CH3), 30.82 (C-3), 38.33 (C-4), 47.55 (C-2), 56.50 (OCH3), 117.15 (C-9), 119.68 (C-11), 129.60 (C-6), 132.99 (C-5), 135.34 (C-10), 120.56, 134.98, 135.07, 137.67, 149.13, 159.81 (Cquart-arom.), 181.59, 184.51, 198.89 (C=O). EI-MS (70 eV): m/z = 320 (100%, M+), 305 (15%, M+ - CH3), 292 (35%, M+- CO), 291 (15%, M+ - HCO), 261 (27%, 292 - OCH3), 233 (24%, 261 - CO).