An Efficient Synthetic Route to Homocarbonyltopsentine

Abstract

Efficient synthesis of homocarbonyltopsentine Ia, starting from readily available triiodoimidazole 9 and 3-formylindoles 2 and 18 is described. The key steps of the synthesis are selective halogen-metal exchanges at the imidazole nucleus and subsequent addition to formylated indoles.

indoles - metalation - regioselectivity - addition reactions - alkaloids

References

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11

All new compounds gave satisfactory spectroscopic and analytical data. Selected spectroscopic data: 16: white solid, mp >210 °C; IR (KBr): 3198, 1609, 1590, 1512, 1415, 1110, 859 cm^-1; ¹H NMR (300 MHz, DMSO-d ₆): δ 7.22-7.30 (m, 4 H, H_Ar), 7.53-7.59 (m, 2 H, H_Ar), 8.02 (s, 1 H, H_Ar), 8.37-8.40 (m, 2 H, H_Ar), 8.97 (s, 1 H, H_Ar), 9.14 (s, 1 H, H_Ar), 12.00 (s, 1 H, NH), 12.21 (s, 1 H, NH), 13.70 (s, 1 H, NH); ¹³C NMR (75 MHz, DMSO-d ₆): δ 112.2 (CH), 112.5 (CH), 113.4 (C), 114.9 (C), 121.6 (CH), 121.7 (2 CH), 122.3 (CH), 122.9 (CH), 123.2 (CH), 124.3 (CH), 126.5 (C), 126.7 (C), 135.7 (CH), 136.2 (C), 136.3 (C), 137.1 (CH), 143.3 (C), 145.5 (C), 176.5 (CO), 181.6 (CO); MS (ESI): m/z 355 (M + H⁺); HRMS (LSIMS) for C₂₁H₁₅N₄O₂: calculated: 355.1195, found: 355.1195. Ia: yellow solid, mp >210 °C; IR (KBr): 3380, 3200, 1592, 1572, 1525, 1430, 1120, 868 cm^-1; ¹H NMR (300 MHz, DMSO-d ₆): δ 6.78 (dd, 1 H, J = 1.7 Hz, 8.6 Hz, H_Ar), 6.92 (br s, 1 H, H_Ar), 7.20-7.28 (m, 2 H, H_Ar), 7.53-7.56 (m, 1 H, H_Ar) 8.01 (s, 1 H, H_Ar), 8.15 (d, 1 H, J = 8.6 Hz, H_Ar), 8.38-8.41 (m, 1 H, H_Ar), 8.96 (br s, 2 H, H_Ar), 9.33 (s, 1 H, OH), 11.84 (s, 1 H, NH), 11.99 (s, 1 H, NH), 13.63 (s, 1 H, NH); ¹³C NMR (75 MHz, DMSO-d ₆): δ 97.6 (CH), 112.2 (CH), 112.3 (CH), 113.6 (C), 114.9 (C), 119.4 (C), 121.7 (CH), 121.8 (CH), 122.1 (CH), 122.9 (CH), 124.2 (CH), 126.8 (C), 135.7 (CH), 135.9 (CH), 136.2 (C), 137.6 (C), 143.3 (C), 145.6 (C), 154.4 (C), 176.3 (CO), 181.6 (CO); MS (ESI): m/z 371 (M + H⁺); HRMS (LSIMS) for C₂₁H₁₅N₄O₃: calculated: 371.1144, found: 371.1143.

12 Synthesised by formylation (POCl₃, DMF) and protection (Boc₂O, DMAP, acetonitrile) of 6-benzyloxyindole prepared according to; Moody CJ. J. Chem. Soc., Perkin Trans. 1  1984,  1333