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Synlett 2004(8): 1414-1418  
DOI: 10.1055/s-2004-829053
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Simple Biomimetic Route to Nonsymmetric Pyrazines

Edgar Haak*, Ekkehard Winterfeldt
Department of Organic Chemistry, University of Hannover, Schneiderberg 1B, 30167 Hannover, Germany
Fax: +49(531)3915388; e-Mail: e.haak@tu-bs.de;
Further Information

Publication History

Received 17 October 2003
Publication Date:
08 June 2004 (online)

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Abstract

The condensation of enaminoketone 8 to α-hydroxyketones gives rise to nonsymmetric pyrazines. This may be of relevance for the biosynthesis of this heterocycle in the cephalostatins and ritterazines.

Key words

hydroxyketones - pyrazine synthesis - cephalostatins - biosynthesis - pyrylium salts

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25

The low yield observed may well be due to methanolysis of the O-acetate under the reaction conditions.

26

It is mentioned in passing that the well-known oxidative degradation of the furan ring [28] to a carboxylic acid could lead to pyrazine bis-carboxylic acids and derivatives thereof.

27

Reaction Procedure to Form Nonsymmetric Pyrazine 29: Enaminoketone 13 9 (80 mg, 0.18 mmol) and NH4OAc (35 mg, 0.45 mmol) were dissolved in moist MeOH (5 mL, <0.1% H2O) and refluxed for 30 min. A solution of α-hydroxyketone 28 (80 mg, 0.18 mmol) in CH2Cl2 (0.6 mL) was added and the resulting suspension was refluxed for additional 90 min. The mixture was quenched with H2O, extracted with CH2Cl2, and the organic layer was washed with brine and dried over MgSO4. After removal of the solvent, the residue was purified by column chromatography on silica gel to give 29 (43 mg, 28%) as a white solid. 1H NMR (400 MHz, CDCl3): δ = 5.48 (s br, 1 H), 4.78 (dd, J = 7.9 Hz, 2.0 Hz, 1 H), 4.40-4.34 (m, 1 H), 3.56-3.47 (m br, 2 H), 3.44-3.33 (m, 2 H), 1.33 (s, 3 H), 1.09 (s, 3 H), 1.07 (d, J = 6.9 Hz, 3 H), 1.05 (d, J = 6.9 Hz, 3 H), 0.92 (s, 3 H), 0.89 (s, 3 H), 0.81 (d, J = 6.1 Hz, 3 H), 0.79 (d, J = 6.1 Hz, 3 H). 13C NMR (100 MHz, DEPT, CDCl3): δ = 212.88 (s), 210.61 (s), 154.27 (s), 148.52 (s), 148.33 (s), 148.27 (s), 148.09 (s), 121.54 (d), 109.28 (s), 107.04 (s), 83.92 (d), 79.13 (d), 67.10 (t), 66.89 (t), 62.27 (s), 55.65 (d), 55.01 (s), 54.79 (d), 53.53 (d), 53.08 (d), 49.73 (d), 45.25 (t), 45.11 (t), 44.19 (d), 42.22 (d), 41.59 (d), 41.23 (d), 37.62 (t), 37.18 (t), 36.34 (s), 36.12 (s), 35.28 (t), 35.22 (t), 34.18 (d), 33.92 (d), 31.42 (t), 31.24 (t), 31.17 (2 t), 30.30 (d), 30.18 (d), 29.69 (t), 29.12 (t), 28.78 (t), 28.08 (t), 27.86 (t), 20.73 (q), 17.15 (q), 17.13 (q), 15.92 (q), 13.76 (q), 13.22 (q), 11.69 (q), 11.47 (q). MS-FAB (NBA matrix): m/z (%) = 846 (100)[M+], 828 (19), 732 (20), 154 (33) [NBA matrix].