Transition Metals in Organic Synthesis, Part 111:^[1] First Total Synthesis and Structural Revision of Antipathine A

Abstract

We describe the first total synthesis of antipathine A and a revision of the original structural assignment.

Key words

alkaloids - catalysis - cyclisation - palladium

• References and Notes

• 1 Part 110: Kumar, V. P.; Gruner, K. K.; Kataeva, O.; Knölker, H.-J. Angew. Chem. Int. Ed. 2013, 52, doi: 10.1002/anie.201305993.

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• 11 Spectroscopic Data for 2,4-Dimethyl-4,7-dihydro-1H-pyrimido[4,5-c]carbazole-1,3(2H)-dione (13) Light yellow solid; mp 307–309 °C. UV (MeOH): λ = 217, 257, 275 (sh), 334, 374, 392 nm. Fluorescence (MeOH): λ_ex = 257 nm, λ_em = 434, 518 nm. IR (ATR): ν = 3278, 3045, 2951, 2921, 2056, 2030, 2009, 1734, 1688, 1631, 1582, 1517, 1489, 1458, 1418, 1345, 1317, 1288, 1222, 1184, 1139, 1079, 1025, 987, 924, 862, 791, 742, 721, 698, 637, 606 cm^–1. ¹H NMR (500 MHz, C₅D₅N): δ = 3.56 (s, 3 H), 3.65 (s, 3 H), 7.32 (d, J = 8.9 Hz, 1 H), 7.45 (t, J = 7.7 Hz, 1 H), 7.60 (ddd, J = 8.1, 7.0, 1.1 Hz, 1 H), 7.73 (d, J = 8.1 Hz, 1 H), 7.98 (d, J = 8.9 Hz, 1 H), 10.27 (d, J = 8.4 Hz, 1 H), 12.90 (br s, 1 H). ¹³C NMR (125 MHz, C₅D₅N): δ = 28.71 (CH₃), 31.73 (CH₃), 110.96 (C), 111.45 (CH), 112.49 (CH), 118.68 (CH), 119.26 (CH), 120.91 (C), 123.20 (C), 127.29 (CH), 129.22 (CH), 136.28 (C), 137.32 (C), 142.72 (C), 151.07 (C=O), 162.83 (C=O). MS (70 eV): m/z (%) = 279 (100) [M⁺], 222 (12), 221 (6), 194 (22), 193 (30), 167 (8), 166 (12), 139 (7). HRMS: m/z calcd for C₁₆H₁₃N₃O₂ [M⁺]: 279.1008; found: 279.0999.
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• 13 Spectroscopic Data for Antipathine A {1,3-Dimethyl-1H-pyrimido[5,4-b]carbazole-2,4(3H,6H)-dione} (2) Yellow solid; mp 342–344 °C. UV (MeOH): λ = 219, 260, 318 (sh), 327, 383, 398 nm. Fluorescence (MeOH): λ_ex = 260 nm, λ_em = 448 nm. IR (ATR): ν = 3263, 3028, 2921, 2846, 1771, 1735, 1717, 1686, 1626, 1559, 1540, 1518, 1456, 1432, 1377, 1333, 1307, 1241, 1191, 1146, 1098, 1067, 1017, 965, 856, 834, 765, 742, 723, 706, 640 cm^–1. ¹H NMR (500 MHz, C₅D₅N): δ = 3.57 (s, 3 H), 3.66 (s, 3 H), 7.35 (t, J = 7.4 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.66 (d, J = 8.2 Hz, 1 H), 8.14 (s, 1 H), 8.41 (d, J = 7.8 Hz, 1 H), 8.65 (s, 1 H), 12.72 (br s, 1 H). ¹³C NMR (125 MHz, C₅D₅N): δ = 28.51 (CH₃), 31.03 (CH₃), 104.87 (CH), 110.19 (CH), 112.03 (CH), 114.50 (C), 119.62 (CH), 122.18 (CH), 122.91 (C), 128.46 (CH), 129.76 (C), 133.94 (C), 136.74 (C), 143.60 (C), 151.09 (C=O), 162.71 (C=O). MS (70 eV): m/z (%) = 279 (100) [M⁺], 222 (10), 221 (5), 194 (18), 193 (36), 192 (5), 167 (10), 166 (12), 139 (7). HRMS: m/z calcd for C₁₆H₁₃N₃O₂ [M⁺]: 279.1008; found: 279.1001.

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