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Synlett 2006(17): 2777-2780  
DOI: 10.1055/s-2006-950254
LETTER
© Georg Thieme Verlag Stuttgart · New York

Design and Synthesis of Angucyclinone 5-Aza Analogues

Jaime A. Valderrama*, M. Florencia González, Pamela Colonelli, David Vásquez
Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago, Chile
Fax: +56(2)6864744; e-Mail: jvalderr@uc.cl;
Further Information

Publication History

Received 3 July 2006
Publication Date:
09 October 2006 (online)

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Abstract

A highly efficient one-pot procedure for the synthesis of phenanthridine-1,7,10-triones from acylbenzoquinones and cyclic enaminones is reported. The cycloaddition reactions of these quinones with 1-trimethylsilyloxybutadiene followed by hydrolysis and oxidative processes provide entry to a variety of angucyclinone 5-aza analogues.

Key words

Michael additions - quinones - heterocycles - Diels-Alder reactions - regioselectivity

    References and Notes

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11

Synthesis of 3,3,6-Trimethyl-2 H -3,4-dihydro­phen­-anthridine-1,7,10-trione (5d); Typical Procedure. A suspension of 2,5-dihydroxyacetophenone (1b; 152 mg, 1.0 mmol), 3-amino-5,5-dimethyl-2-cyclohexen-1-one (2b; 139 mg, 1.0 mmol), silver(I) oxide (464 mg, 2.0 mmol), MgSO4 (420 mg) and CH2Cl2 (20 mL) was vigorously stirred for 2 h at r.t. The mixture was filtered and the filtrate was evaporated under vacuum to give crude quinone 5d (214 mg, 0.8 mmol, 80%). Further column chromatography of the crude product (silica; CH2Cl2-EtOAc, 9:1) yielded pure 5d (175 mg, 0.65 mmol, 65%) as a yellow solid; mp 131-132 °C; R f 0.49 (silica; CH2Cl2-EtOAc, 9:1). IR (KBr): 2969 (w), 1694 (s), 1668 (vs), 1610 (w), 1556 (s), 1469 (w), 1437 (w), 1391 (m), 1373 (m), 1359 (w), 1338 (s), 1311 (m), 1258 (s), 1225 (s), 1182 (w), 1155 (w), 1110 (m), 1052 (m) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.15 (s, 6 H), 2.75 (s, 2 H), 2.97 (s, 3 H), 3.06 (s, 2 H), 6.86 (d, J = 10.3 Hz, 1 H), 7.05 (d, J = 10.3 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 26.22 (CH3), 28.73 (2 × CH3), 33.51 (C), 47.47 (CH2), 53.28 (CH2), 123.57 (C), 126.08 (C), 138.09 (CH), 138.48 (CH), 141.57 (C), 163.53 (C), 165.66 (C), 184.78 (C), 184.91 (C), 196.96 (C). Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.22; H, 5.50; N, 5.19.

16

Synthesis of Benzo[ j ]phenanthridine-1,7,12-trione 7h; Typical Procedure for Method B: A solution of 6d (105 mg, 0.25 mmol), HCl acid (3 drops, 5%) in aq THF (6 mL, 90%) was left at r.t. for 1 h. The mixture was diluted with H2O (10 mL) and then extracted with CHCl3 (2 × 15 mL). The organic layer was washed with H2O (2 × 10 mL), dried over MgSO4, and evaporated under vacuum. The residue was dissolved in CH2Cl2 (10 mL) and the solution was added to a stirred solution of pyridinium chlorochromate (412 mg, 1.91 mmol), NaOAc (95 mg, 1.16 mmol) in CH2Cl2 (10 mL), and the mixture was stirred for 1.5 h at r.t. The resulting mixture was chromatographed (silica; CH2Cl2-EtOAc, 9:1) to give pure 7h (65.4 mg, 0.195 mmol, 78%) as an orange solid; mp 166-167 °C (dec.); R f 0.14 (silica; CH2Cl2-EtOAc, 9:1). IR (KBr): 3449 (w), 1708 (s), 1678 (s), 1636 (vs), 1571 (s), 1447 (s), 1367 (m), 1333 (s), 1283 (s), 1270 (s), 1243 (m) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.15 (s, 6 H), 2.77 (s, 2 H), 3.07 (s, 5 H), 7.28 (m, 1 H), 7.60 (m, 2 H), 12.30 (s, 1 H). 13C NMR (100 MHz, CDCl3): δ = 27.33 (CH3), 28.80 (2 × CH3), 47.5 (CH2), 53.3 (CH2), 116.1 (C), 119.0 (CH), 124.5 (CH), 125.0 (C), 127.0 (C), 134.3 (C), 136.8 (CH), 144.4 (C), 162.0 (C), 164.5 (C), 166.0 (C), 183.6 (C), 189.0 (C), 197.0 (C). Anal. Calcd for C20H17NO4: C, 71.63; H, 5.11; N, 4.18. Found: C, 71.45; H, 4.94; N, 4.21.