Efficient Method for the Large-Scale Preparation of a Boswellic Acid
followed by flash chromatography with RP-18 silica gel (methanol/
FULL PAPER
8.0 g from 25 g of crude resin acids. M.p. 194Ϫ195 °C (decompo-
water, 9:1). After evaporation of the methanol in vacuo, the aque- sition; ref.[7c] 195 °C; ref.[8d] 197Ϫ198 °C). [α]2D0 ϭ ϩ121 (c ϭ 1.11,
ous residue was extracted with dichloromethane (3 ϫ 100 mL).
Drying of the combined organic extracts with MgSO4, filtration
and evaporation of the solvents gave 7.8 g of a white foam of pure
BA (purity Ͼ 98% as estimated by NMR spectroscopy and HPLC).
CHCl3) (ref.[7c] ϩ129; c ϭ 4.2, CHCl3; ref.[8d] ϩ79; c ϭ 1.0, CHCl3).
1H NMR (CDCl3, 500.13 MHz): δ ϭ 5.54 (s, 1 H, H12), 4.07 (t,
J ϭ 2.8 Hz, 1 H, H3), 2.51 (dt, J ϭ 13.2 Hz, 3.5 Hz, 1 H, H1β),
2.42 (s, 1 H, H9), 2.30 (t br. t, 14.5 Hz, 3.5 Hz, 1 H, H2β), 2.08
M.p. 232Ϫ236 °C (decomposition; ref.[7c] 228Ϫ230 °C; ref.[8d] (td, J ϭ 13.6 Hz, 4.7 Hz, 1 H, H16β), 1.92Ϫ184 (m, 2 H, H15β,
227Ϫ229). [α]2D0 ϭ ϩ86 (c ϭ 0.54, CHCl3) (ref.[7c] ϩ108; c ϭ 2.59, H6β), 1.71 (m, 1 H, H6α), 1.65 (dd, J ϭ 12.9 Hz, 4.1 Hz, 1 H,
CHCl3; ref.[8d] ϩ112.7; c ϭ 0.7, CHCl3). 1H NMR (CDCl3, H7α), 1.57Ϫ1.51 (m, 2 H, H2α, H18), 1.49Ϫ1.41 (m, 4 H, H5,
500.13 MHz): δ ϭ 5.14 (t, J ϭ 3.5 Hz, 1 H, H12), 4.08 (t, 2.8 Hz,
H7β, H21α, H22β), 1.39Ϫ1.37 (m, 1 H, H19), 1.35 (d, J ϭ 3.8 Hz,
1 H, H3), 2.23 (tdd, J ϭ 14.5 Hz, 4.2 Hz, 2.8 Hz, 1 H, H2β), 2.01 1 H, H22α), 1.33 (s, 3 H, H23), 1.32 (br. d, J ϭ 3.2 Hz, 2 H, H1α,
(td, J ϭ 13.6 Hz, 4.7 Hz, 1 H, H16α), 1.96Ϫ1.89 (m, 2 H, H11α, H21β), 1.30 (s, 3 H, H27), 1.22 (br. d, 3.5 Hz, 1 H, H15α), 1.17 (s,
H11β), 1.88Ϫ1.78 (m, 2 H, H6β, H15β), 1.73Ϫ1.67 (m, 1 H, H6α), 3 H, H26), 1.12 (s, 3 H, H25), 1.00 (br. d, J ϭ 13.6 Hz, 1 H, H16β),
1.63Ϫ1.52 (m, 3 H, H2α, H7α, H9), 1.51Ϫ1.46 (m, 2 H, H1β, H5), 0.93 (br. s, 4 H, H20, H30), 0.81 (s, 3 H, H28), 0.78 (d, J ϭ 6.3 Hz,
1.44Ϫ1.36 (m, 3 H, H7β, H21β, H22α), 1.36Ϫ1.34 (m, 1 H, H19),
1.35 (s, 3 H, H23), 1.32 (br. s, 2 H, H1α, H18), 1.30Ϫ1.24 (m, 2 H,
H21α, H22β), 1.09 (s, 3 H, H27), 1.05 (s, 3 H, H26), 1.03Ϫ0.98 (m,
1 H, H15α), 0.93Ϫ0.91 (m, 1 H, H20), 0.921 (d, J ϭ 6.0 Hz, 3 H,
3 H, H29) ppm. 13C NMR (CDCl3, 90.56 MHz): δ ϭ 199.4 (C11,
ϾCO), 182.7 (C24, COOH), 164.9 (C13, ϭCϽ), 130.6 (C12,
HϾCϭ), 70.5 (C3, ϾCH-OH), 60.5 (C9, ϾCH-), 59.1 (C18,
ϾCH-), 48.9 (C5, ϾCH-), 47.3 (C4, ϾCϽ), 45.1 (C8, ϾCϽ), 43.8
H30), 0.89Ϫ0.86 (m, 1 H, H16β), 0.81 (s, 3 H, H28), 0.79 (d, J ϭ (C14, ϾCϽ), 40.9 (C22, -CH2-), 39.31 (C19, ϾCH-), 39.3 (C20,
6.0 Hz, 3 H, H29) ppm. 13C NMR (CDCl3, 90.56 MHz): δ ϭ 183.4 ϾCH-), 37.6 (C10, ϾCϽ), 34.0 (C17, ϾCϽ), 33.9 (C1, -CH2-), 32.9
(C24, COOH), 139.5 (C13, ϭCϽ), 124.4 (C12, HϾCϭ), 70.7 (C3, (C7, -CH2-), 30.9 (C21, -CH2-), 28.9 (C28, -CH3), 27.6 (C16,
ϾCH-OH), 59.0 (C18, ϾCH-), 49.0 (C5, ϾCH-), 47.3 (C4, ϾCϽ),
-CH2-), 27.2 (C15, -CH2-), 26.3 (C2, -CH2-), 24.3 (C23, -CH3), 21.1
46.7 (C9, ϾCH-), 42.2 (C14, ϾCϽ), 41.5 (C22, -CH2-), 39.9 (C8, (C30, -CH3), 20.6 (C27, -CH3), 18.9 (C6, -CH2), 18.4 (C26, -CH3),
ϾCϽ), 39.6 (C19, ϾCH-), 39.5 (C20, ϾCH-), 37.5 (C10, ϾCϽ), 17.4 (C29, -CH3), 13.2 (C25, -CH3) ppm. EI-MS (70 eV, 200 °C):
33.8 (C1, -CH2-), 33.7 (C17, ϾCϽ), 33.0 (C7, -CH2-), 31.2 (C21, m/z ϭ 470 (18) [Mϩ], 287 (10), 273 (100), 232 (51), 135 (25).
-CH2-), 28.8 (C28, -CH3), 28.0 (C16, -CH2-), 26.4 (C15, -CH2-), HRMS: calculated: 470.33960; found 470.33945.
26.1 (C2, -CH2-), 24.2 (C23, ϾCH-), 23.4 (C11, -CH2-), 23.2 (C27, -
CH3), 21.4 (C30, -CH3), 19.6 (C6, -CH2-), 17.4 (C29, -CH3), 16.8
(C26, -CH3), 13.2 (C25, -CH3) ppm. EI-MS (70 eV, 175 °C): m/z ϭ
456 (11) [Mϩ], 238 (17), 218 (100), 203 (14), 189 (11), 133 (11), 109
(10), 95 (12). HRMS: calculated: 456.36035; found 456.35981.
Acknowledgments
This work was generously supported by the Bund der Freunde
der Technischen Universität München and by the Deutsche
Forschungsgemeinschaft. We thank BASF AG, Ludwigshafen,
Germany and Pfizer AG, Karlsruhe, Germany, for chemicals and
laboratory equipment.
3-O-Acetyl-β-boswellic Acid (1b): This compound was obtained by
a combination of the procedures above according to Scheme 3.
Yield: 8.5 g from 25 g of crude resin acids. M.p. 251Ϫ253 °C (de-
composition; ref.[7c] 253 °C; ref.[8d] 254Ϫ256 °C). [α]2D0 ϭ ϩ54 (c ϭ
1.00, CHCl3) (ref.[7c] ϩ47; c ϭ 2.58, CHCl3; ref.[8d] ϩ141; c ϭ 0.4,
1
CHCl3). H NMR (CDCl3, 500.13 MHz): δ ϭ 5.14 (t, J ϭ 3.5 Hz,
[1]
Inflammation Ϫ Basic Principles and Clinical Correlates (Eds.:
1 H, H12), 5.30 (t, 2.8 Hz, 1 H, H3), 2.14 (m, 1 H, H2β), 2.10 (s,
3 H, H32), 2.01 (td, J ϭ 13.6 Hz, 4.7 Hz, 1 H, H16α), 1.95Ϫ1.89
(m, 2 H, H11α, H11β), 1.88Ϫ1.77 (m, 2 H, H6β, H15β), 1.74Ϫ1.68
(m, 1 H, H6α), 1.67Ϫ1.62 (m, 1 H, H2α), 1.60 (dd, J ϭ 10.1 Hz,
7.3 Hz, 1 H, H9), 1.57Ϫ1.47 (m, 2 H, H1β, H7α), 1.47Ϫ1.41 (m, 3
H, H5, H7β, H22α), 1.41Ϫ1.35 (m, 1 H, H21β), 1.35Ϫ1.30 (m, 2
H, H18, H19), 1.30Ϫ1.25 (m, 2 H, H21α, H22β), 1.24 (s, 3 H,
H23), 1.22Ϫ1.16 (m, 1 H, H1α), 1.12 (s, 3 H, H27), 1.04 (s, 3 H,
H26), 1.04Ϫ0.98 (m, 1 H, H15α), 0.92 (d, J ϭ 6.0 Hz, 3 H, H30),
0.90 (s, 3 H, H25), 0.92Ϫ0.85 (m, 2 H, H16β, H20), 0.80 (s, 3 H,
H28), 0.79 (d, J ϭ 7.0 Hz, 3 H, H29) ppm. 13C NMR (CDCl3,
90.56 MHz): δ ϭ 182.5 (C24, COOH), 170.3 (C31, CϭO acetyl),
139.5 (C13, ϭCϽ), 124.5 (C12, HϾCϭ), 73.2 (C3, ϾCHO-), 59.2
(C18, ϾCH-), 50.6 C5, ϾCH-), 46.8 (C9, ϾCH-), 46.7 (C4, ϾCϽ),
42.7 (C14, ϾCϽ), 41.5 (C22, -CH2-), 40.0 (C8, ϾCϽ), 39.8 (C19,
ϾCH-), 39.6 (C20, ϾCH-), 37.4 (C10, ϾCϽ), 34.5 (C1, -CH2-),
33.8 (C17, ϾCϽ), 33.1 (C7; -CH2-), 31.3 (C21, -CH2-), 28.8 (C28;
-CH3), 28.1 (C16, -CH2-), 26.6 (C15, -CH2-), 23.7 (C23, ϾCH3),
23.6 (C2, -CH2), 23.4 (C11, -CH2-), 23.3 (C27, -CH3), 21.4 (C30, -
CH3), 21.3 (C32, -CH3 acetyl), 19.6 (C6, -CH2-), 17.5 (C29, -CH3),
16.9 (C26, -CH3), 13.3 (C25, -CH3) ppm. EI-MS (70 eV, 220 °C):
m/z ϭ 498 (8 Mϩ), 218 (100), 203 (13), 95 (13). HRMS: calculated:
498.37091; found 498.37158.
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11-Oxo-β-boswellic Acid (1c): This compound was obtained by a
combination of the procedures above according to Scheme 3. Yield:
Eur. J. Org. Chem. 2003, 4752Ϫ4756
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4755