References and Notes
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8 In the synthetic work published in ref. 3, discriminating between the two primary hydroxyl groups was achieved by an enzymatic acetylation towards substrate 3 and diastereoisomeric monoacetate of diol 3 was obtained with a ratio of 13: 1. In our case, bromoetherification of diol 3 led to only desired diastereisomer 15.
9a
Hoffmann RW.
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12 Natural paeonilide was provided by professor J. K. Liu. The optical rotation of synthetic paeonilide compared well to the value of authentic sample.
13 Compound 3: colorless solid; mp 84-85 °C; [α]D
20 -101.6 (c 0.993, CHCl3). IR (film): 3424 (s), 2928 (m), 1632 (m), 1372 (m), 1297 (m), 1281 (m), 1237 (w), 1136 (s), 1099 (w), 1071 (w), 1034 (w) cm-1. 1H NMR (300 MHz, CDCl3): δ = 5.67 (1 H, dd, J = 3.9, 10.4 Hz), 5.58 (1 H, d, J = 10.4 Hz), 4.03 (1 H, br s), 3.92-3.74 (4 H, m), 3.12 (1 H, br s), 2.70 (1 H, br s), 2.49-2.20 (2 H, m), 1.96 (1 H, m), 1.91 (1 H, ddd, J = 2.8, 8.3, 15.6 Hz), 1.38 (3 H, s), 1.35 (3 H, s), 1.30 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 131.7 (d), 128.9 (d), 108.5 (s), 78.3 (d), 77.6 (s), 64.4 (t), 63.9 (t), 46.6 (d), 30.1 (d), 28.3 (q), 27.9 (q), 25.1 (q), 24.9 (t). MS (EI): m/z (%) = 242 (3) [M+], 227 (3), 211 (5), 191 (13), 167 (52), 149 (36), 105 (91), 57 (100). HRMS: m/z calcd for C13H22O4Na [M + 23]+: 265.1415; found: 265.1416.
Compound 15: colorless oil; [α]D
20 -4.9 (c 0.745, CHCl3). IR (KBr): 3443 (br s), 2985 (s), 2937 (s), 2876 (s), 1458 (s), 1380 (s), 1256 (s), 1215 (s), 1103 (s), 1071 (s), 1029 (s), 990 cm-1. 1H NMR (300 MHz, CDCl3): δ = 4.20-4.06 (4 H, m), 3.70-3.57 (3 H, m), 2.28-2.12 (4 H, m), 1.77-1.65 (1 H, m), 1.48 (3 H, s), 1.43 (3 H, s), 1.41 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 109.5 (s), 83.3 (d), 81.1 (s), 79.4 (d), 69.6 (t), 63.4 (t), 61.3 (d), 48.7 (d), 38.4 (d), 30.9 (t), 28.3 (q), 26.4 (q), 23.3 (q). MS (EI): m/z (%) = 322 (3) [M+], 320 (2) [M+], 307 (8), 305(7), 197 (7), 183 (10), 169 (12), 155 (16), 127 (27), 111 (27), 97 (38), 85 (64), 71 (100). HRMS: m/z calcd for C13H22O4Na [M + 23]+: 343.0520; found: 343.0529.
Compound 16: colorless oil; [α]D
20 -5.7 (c 0.764, CHCl3). IR (KBr): 2981 (s), 2953 (s), 2876 (s), 1724 (s), 1688 (s), 1602 (m), 1582 (m), 1453 (s), 1424 (s), 1380 (s), 1325 (s), 1285 (s), 1211 (s), 1180 (s), 1113 (s), 1056 (s), 934 (s), 708 (s) cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.98 (2 H, d, J = 7.5 Hz), 7.55 (1 H, t, J = 7.5 Hz), 7.43 (2 H, t, J = 7.5 Hz), 4.33-4.05 (6 H, m), 3.63 (1 H, dd, J = 6.9, 9.3 Hz), 2.44 (1 H, m), 2.26-2.17 (2 H, m), 1.72 (1 H, m), 1.45 (3 H, s), 1.40 (3 H, s), 1.37 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 166.7 (s), 133.7 (d), 130.1 (s), 129.9 (d), 128.9 (d), 109.9 (s), 83.6 (d), 81.4 (s), 79.7 (d), 69.9 (t), 65.4 (t), 61.2 (d), 46.2 (d), 39.5 (d), 31.3 (t), 28.7 (q), 26.8 (q), 23.7 (q). MS (EI): m/z (%) = 426 (14) [M+], 424 (15) [M+], 411 (30), 409 (32), 351 (5), 349 (5), 329 (3), 287 (4), 229 (13), 227 (15), 183 (6), 165 (19), 147 (22), 105(100). HRMS: m/z calcd for C20H25O5NaBr [M + 23]+: 447.0783; found: 447.0774.
Compound 17: colorless oil; [α]D
20 +23.4 (c 1.161, CHCl3). IR (KBr): 3453 (br s), 2977 (s), 2940 (s), 2889 (s), 1719 (s), 1601 (w), 1451 (s), 1394 (s), 1376 (s), 1274 (s), 1117 (s), 1069 (s), 1026 (s), 756 (s), 713 (s) cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.01 (2 H, d, J = 7.5 Hz), 7.57 (1 H, t, J = 7.5 Hz), 7.44 (2 H, t, J = 7.5 Hz), 4.43 (1 H, d, J = 7.5 Hz), 4.39 (1 H, dd, J = 5.7, 11.2 Hz), 4.29 (1 H, dd, J = 4.4, 6.7 Hz), 4.23 (1 H, d, J = 9.2 Hz), 4.21 (1 H, d, J = 9.3 Hz), 3.94 (1 H, t, J = 4.5 Hz), 3.73 (1 H, dd, J = 7.2, 9.0 Hz), 3.37 (1 H, br s), 2.98 (1 H, m), 2.37 (1 H, m), 2.01-1.90 (2 H, m), 1.33 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 166.5 (s), 133.2 (d), 129.8 (s), 129.6 (d), 128.4 (d), 82.5 (d), 74.2 (d), 72.3 (s), 69.6 (t), 65.2 (t), 42.5 (d), 39.6 (d), 28.2 (t), 22.8 (q), 14.2 (q). MS (EI): m/z (%) = 323 (1), 305(3), 287 (30), 264 (10), 262 (11), 217 (7), 183 (13), 165 (86), 147 (36), 138 (26), 123 (26), 105 (100). HRMS: m/z calcd for C17H21O5NaBr [M + 23]+: 407.0470; found: 407.0463.
Compound 18: colorless oil. 1H NMR (300 MHz, CDCl3): δ = 9.82 (1 H, d, J = 1.5 Hz), 8.03 (2 H, d, J = 7.8 Hz), 7.58 (1 H, t, J = 7.9 Hz), 7.45 (2 H, t, J = 7.9 Hz), 4.82 (1 H, dd, J = 6.3, 8.6 Hz), 4.31-4.20 (2 H, m), 4.00-3.86 (3 H, m), 3.25 (1 H, ddd, J = 3.0, 8.9, 9.0 Hz), 2.52-2.33 (3 H, m), 1.48 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 200.4 (s), 166.8 (s), 133.6 (d), 130.2 (s), 130.0 (d), 128.9 (d), 90.4 (d), 82.1 (s), 70.5 (t), 65.3 (t), 65.0 (d), 62.1 (d), 45.1 (d), 44.2 (d), 24.6 (q).
Compound 22: colorless oil; [α]D
20 +50.7 (c 0.725, CHCl3). IR (KBr): 3442 (br s), 2949 (w), 2892 (w), 1721 (s), 1601 (w), 1451 (w), 1275 (s), 1112 (s), 1071 (w), 1045 (w), 713 (s) cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.98 (2 H, d, J = 8.4 Hz), 7.56 (1 H, t, J = 7.5 Hz), 7.44 (2 H, dd, J = 7.5, 8.4 Hz), 4.51 (1 H, dd, J = 7.1, 8.3 Hz), 4.33 (2 H, d, J = 6.0 Hz), 4.22 (1 H, t, J = 9.0 Hz), 4.08 (1 H, d, J = 9.0 Hz), 3.79 (1 H, dd, J = 8.0, 9.1 Hz), 2.93 (1 H, dd, J = 8.0, 16.5 Hz), 2.80-2.67 (2 H, m), 2.49-2.37 (1 H, m), 1.43 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 208.0 (s), 166.4 (s), 133.5 (d), 129.8 (s), 129.7 (d), 128.7 (d), 82.2 (d), 76.6 (s), 69.5 (t), 64.4 (t), 59.9 (d), 43.5 (t), 41.3 (d), 36.6 (q), 22.5 (q). MS (EI): m/z (%) = 303 (15), 285 (4), 274 (5), 257 (3), 189 (8), 181 (48), 163 (13), 153 (14), 138 (20), 121 (11), 105 (100), 95 (13), 77 (24). HRMS: m/z calcd for C17H19O5NaBr [M + 23]+: 405.0313; found: 405.0322.
Compound 23: colorless oil, mixture of α-bromoketones. 1H NMR (300 MHz, CDCl3): δ = 8.05-8.01 (4 H, m), 7.58 (2 H, t, J = 7.5 Hz), 7.48-7.43 (4 H, m), 4.53-4.27 (8 H, m), 4.18 (1 H, dd, J = 7.8, 9.0 Hz), 3.97 (1 H, d, J = 10.2 Hz), 3.76-3.70 (2 H, m), 3.68 (3 H, s), 3.65 (3 H, s), 2.85-2.62 (4 H, m), 2.50-2.39 (2 H, m), 2.42 (3 H, s), 2.36 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 200.9/200.2 (s), 172.4 (s), 166.7 (s), 133.6 (d), 130.0 (s), 130.0 (d), 128.9 (d), 80.4/80.0 (d), 70.9/70.4 (t), 65.7/65.6 (t), 54.5/49.3 (d), 52.4 (q), 44.6/43.7 (d), 41.3/40.9 (d), 33.8/33.4 (t), 27.7/26.1 (q). MS (EI): m/z (%) = 333 (25), 277 (20), 259 (6), 211 (30), 179 (15), 155 (35), 151 (29), 105(100). HRMS: m/z calcd for C18H21O6NaBr [M + 23]+: 435.0419; found: 435.0421.
Compound 1 (R = Me): colorless oil, [α]D
20 +58.8 (c 1.822, acetone). 1H NMR (300 MHz, CDCl3): δ = 8. 01 (2 H, d, J = 7.2 Hz), 7.56 (1 H, t, J = 7.5 Hz), 7.43 (2 H, dd, J = 7.2, 7.5 Hz), 5.82 (1 H, s), 4.39 (1 H, dd, J = 6.0, 9.6 Hz), 4.32-4.21 (3 H, m), 3.93 (1 H, dd, J = 3.0, 11.7 Hz), 3.67 (3 H, s), 2.93 (1 H, dd, J = 3.0, 16.5 Hz), 2.78 (1 H, q, J = 6.0 Hz), 2.48 (1 H, dd, J = 10.8, 16.5 Hz), 2.12 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 197.3 (s), 177.5 (s), 172.2 (s), 166.7 (s), 133.6 (d), 130.1 (s), 130.0 (d), 128.8 (d), 99.7 (d), 72.4 (t), 65.8 (t), 52.3 (q), 42.6 (d), 42.1 (d), 35.6 (t), 31.7 (q). MS (EI): m/z (%) = 333 (1) [M+ + 1], 290 (2), 259 (5), 247 (5), 210 (22), 193 (12), 137 (15), 105(100). HRMS: m/z calcd for C18H20O6Na [M + 23]+: 355.1157; found: 355.1152.
Paeonilide: colorless needles; [α]D
20 +50.6 (c 0.775, acetone). Authentic sample: [α]D
20 +53.5 (c 0.340, acetone). IR (KBr): 3438 (s), 1763 (s), 1709 (s), 1281 (s), 1119 (s), 1041 (m), 949 (m), 922 (m), 717 (s) cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.01 (2 H, d, J = 7.5 Hz), 7.59 (1 H, t, J = 7.5 Hz), 7.44 (2 H, t, J = 7.5 Hz), 4.29 (1 H, dd, J = 7.2, 11.1 Hz), 4.17 (1 H, dd, J = 8.1, 11.1 Hz), 4.02 (2 H, m), 3.41 (1 H, d, J = 17.8 Hz), 3.34 (1 H, dd, J = 10.5, 18.5 Hz),* 2.96 (1 H, d, J = 18.4 Hz), 2.94 (1 H, m), 2.54 (1 H, dd, J = 2.8, 18.4 Hz),* 2.54 (1 H, m), 2.19 (3 H, s). 13C NMR (75 MHz, CDCl3): δ = 204.5 (s), 174.6 (s), 166.5 (s), 133.6 (d), 129.8 (s), 129.7 (d), 128.7 (d), 115.1 (s), 68.1 (t), 65.1 (t), 49.7 (t), 46.9 (d), 44.5 (d), 36.8 (t), 31.1 (q). MS (EI): m/z (%) = 196 (15), 178 (9), 152 (52), 139 (12), 105(100), 94 (53). HRMS: m/z calcd for C17H18O6Na [M + 23]+: 341.1001; found: 341.1001. *A few typing errors were found for the assignment of protons at C13 position in the original paper published in Biosci. Biotechnol. Biochem. (see ref. 2). It should be corrected as 3.34 (1 H, dd, J = 10.5, 18.5 Hz) and 2.55 (1 H, dd, J = 2.8, 18.5 Hz).