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Synlett 2004(15): 2701-2704  
DOI: 10.1055/s-2004-835625
LETTER
© Georg Thieme Verlag Stuttgart · New York

First Enantiospecific Synthesis of Antileishmanial 12-Deoxyroyleanone from Abietic Acid

E. J. Alvarez-Manzaneda Roldán*a, R. Chahbouna, F. Bentaleba, E. Cabrera Torresa, E. Alvareza, A. Haidoura, J. M. Ramos Lópeza, R. Alvarez-Manzaneda Roldánb, S. El Houssamea
a Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Biotecnología, Universidad de Granada, 18071 Granada, Spain
b Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Almería, 04120 Almería, Spain
Fax: +34(958)248089; e-Mail: eamr@ugr.es;
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Publication History

Received 30 September 2004
Publication Date:
22 October 2004 (online)

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Abstract

12-Deoxyroyleanone (1), an abietane diterpenoid with appreciable antileishmanial activity, has been efficiently synthesized from abietic acid (10; 11 steps for a 25% overall yield).

Key words

enantiospecific synthesis - diterpenoids - antileishmanial activity

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All new compounds were fully characterized spectroscopically and had satisfactory HRMS data. Selected data: Compound 6: 1H NMR (300 MHz, CDCl3): δ = 1.23 (6 H, d, J = 6.9 Hz), 1.23 (3 H, s), 1.40-1.60 (m, 2 H), 1.60-1.95 (m, 5 H), 2.24 (1 H, dd, J = 12.5, 2.0 Hz), 2.30 (1 H, br d, J = 12.7 Hz), 2.79 (1 H, ddd, J = 17.6, 11.3, 6.2 Hz), 2.99 (1 H, dd, J = 17.6, 6.2 Hz), 3.34 (1 H, h, J = 6.9 Hz), 3.67 (3 H, s), 3.73 (3 H, s), 7.02 (1 H, d, J = 8.1 Hz), 7.10 (1 H, d, J = 8.1 Hz). 13C NMR (75 MHz, CDCl3): δ = 16.5 (CH3), 18.6 (CH2), 21.3 (CH2), 23.8 (CH3), 23.9 (CH3), 24.5 (CH3), 25.1 (CH3), 26.0 (CH), 36.6 (CH3), 37.1 (C), 38.1 (CH2), 44.6 (CH), 47.6 (C), 51.9 CH3), 60.4 (CH3), 120.2 (CH), 123.8 (CH), 128.4 (C), 138.0 (C), 148.5 (C), 154.8 (C), 179.0 (C).
Compound 7: 1H NMR (300 MHz, CDCl3): δ = 0.82 (3 H, s), 0.95 (3 H, d, J = 6.9 Hz), 0.98 (3 H, d, J = 6.9 Hz), 1.14 (1 H, dd, J = 12.5, 4.9 Hz), 1.26 (3 H, s), 1.40-2.20 (13 H, m), 3.11 (1 H, h, J = 6.9 Hz), 3.52 (3 H, s), 3.64 (3 H, s), 5.74 (1 H, br s). 13C NMR (75 MHz, CDCl3): δ = 14.1 (CH3), 17.0 (CH3), 18.2 (CH2), 20.5 (CH3), 20.7 (CH3), 22.4 (CH2), 22.7 (CH2), 25.5 (CH2), 26.8 (CH), 34.8 (C), 37.0 (CH2), 38.5 (CH2), 44.8 (CH), 46.6 (C), 51.5 (CH), 51.9 (CH3), 60.5 (CH3), 117.1 (CH), 130.5 (C), 130.7 (C), 147.8 (C), 179.1 (C).
Compound 9: 1H NMR (300 MHz, CDCl3): δ = 0.83 (3 H, s), 0.85 (3 H, d, J = 6.9 Hz), 0.89 (3 H, d, J = 6.9 Hz), 1.22 (3 H, s), 2.05 (1 H, h, J = 6.9 Hz), 3.42 (3 H, s), 3.44 (1 H, br s), 3.60 (3 H, s), 5.66 (1 H, br s). 13C NMR (75 MHz, CDCl3): δ = 15.6 (CH3), 16.5 (CH3), 17.5 (CH3), 18.0 (CH2), 18.2 (CH3), 19.5 (CH2), 25.0 (CH2), 26.6 (CH2), 33.4 (CH), 35.3 (C), 37.1 (CH2), 39.3 (CH2), 44.9 (CH), 46.5 (C), 51.3 (CH), 51.9 (CH3), 60.2 (CH3), 76.3 (C), 83.5 (C), 120.0 (CH), 134.8 (C), 179.3 (C).
Compound 12: 1H NMR (300 MHz, CDCl3): δ = 1.04 (3 H, s), 1.19 (6 H, d, J = 6.9 Hz), 1.38 (3 H, s), 1.60-1.85 (4 H, m), 2.14 (2 H, m), 2.88 (1 H, dd, J = 3.1, 2.8 Hz), 3.28 (1 H, h, J = 6.9 Hz), 3.63 (3 H, s), 3.70 (3 H, s), 5.76 (1 H, dd, J = 9.8, 2.8 Hz), 6.78 (1 H, dd, J = 9.8, 3.1 Hz), 6.90 (1 H, d, J = 8.1 Hz), 7.08 (1 H, d, J = 8.1 Hz). 13C NMR (75 MHz, CDCl3): δ = 17.9 (CH3), 18.5 (CH2), 20.7 (CH3), 23.9 (CH3), 24.0 (CH3), 26.2 (CH), 35.6 (CH2), 35.7 (CH2), 37.5 (C), 44.7 (C), 46.4 (CH), 52.0 (CH3), 62.3 (CH3), 117.8 (CH), 122.6 (CH), 125.7 (CH), 125.7 (C), 129.8 (CH), 139.0 (C), 146.9 (C), 153.4 (C), 178.5 (C).
Compound 15: 1H NMR (400 MHz, CDCl3): δ = 0.93 (3 H, s), 0.96 (3 H, s), 1.18 (3 H, s), 1.21 (3 H, d, J = 6.8 Hz), 1.20 (3 H, d, J = 6.8 Hz), 1.32 (1 H, dd, J = 12.5, 2.1 Hz), 1.39 (1 H, dt, J = 13.1, 3.6 Hz), 1.48 (1 H, br d, J = 13.1 Hz), 1.55-1.85 (8 H, m), 1.93 (1 H, dd, J = 13.2, 7.8 Hz), 2.26 (1 H, br d, J = 12.7 Hz), 2.73 (1 H, ddd, J = 17.7, 11.4, 7.7 Hz), 3.01 (1 H, dd, J = 17.6, 7.7 Hz), 3.28 (1 H, h, J = 6.9 Hz), 3.72 (3 H, s), 7.02 (1 H, d, J = 8.4 Hz), 7.05 (1 H, d, J = 8.4 Hz). 13C NMR (100 MHz, CDCl3): δ = 18.7 (CH2), 19.4 (CH2), 21.7 (CH3), 24.0 (CH3), 23.4 (CH3), 25.0 (CH3), 29.5 (CH2), 26.1 (CH), 33.4 (CH3), 33.4 (C), 37.8 (C), 39.0 (CH2), 41.7 (CH2), 50.2 (CH), 60.5 (CH3), 120.4 (CH), 123.7 (CH), 128.7 (C), 137.8 (C), 149.4 (C), 154.0 (C).
Compound 17: 1H NMR (300 MHz, CDCl3): δ = 0.92 (3 H, s), 0.95 (3 H, s), 1.18 (3 H, s), 1.24 (6 H, d, J = 6.8 Hz), 1.95 (1 H, m), 2.26 (1 H, br d, J = 12.7 Hz), 2.60 (1 H, ddd, J = 16.5, 11.5, 6.2 Hz), 2.80 (1 H, dd, J = 16.5, 6.2 Hz), 3.14 (1 H, h, J = 6.8 Hz), 4.50 (1 H, s), 6.85 (1 H, d, J = 8.2 Hz), 7.01 (1 H, d, J = 8.2 Hz). 13C NMR (75 MHz, CDCl3): δ = 18.5 (CH2), 19.4 (CH2), 21.7 (CH3), 22.6 (CH3), 22.9 (CH3), 24.4 (CH3), 24.9 (CH3), 26.9 (CH), 33.4 (CH3), 33.4 (C), 38.8 (C), 39.0 (CH2), 41.7 (CH2), 49.8 (CH), 116.5 (CH), 123.3 (CH), 130.9 (C), 130.9 (C), 149.1 (C), 150.3 (C).