A Brief Total Synthesis of Eupolauramine

Abstract

A concise synthesis of the alkaloid eupolauramine has been achieved. The key step was a benzotriazolyl-mediated connection of a bromoaryl unit to the azaisoindolinone framework by an enol ether function. Free radical cyclization then provided the natural product.

alkaloids - carbanions - enols - ring closure - total synthesis

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17

All new compounds have been fully characterized. ¹H NMR (300 MHz, CDCl₃), ¹³C NMR and APT spectral data (75 MHz, CDCl₃) and elemental analysis of the key intermediates for Compound 10: white solid, mp 176-177 °C. ¹H NMR: δ = 1.12 (s, 9 H, 3 CH₃), 2.83 (s, 3 H, NCH₃), 5.89 (d, J = 8.3 Hz, 1 H, ArH), 6.15 (d, J = 7.8 Hz, 1 H, ArH), 6.81 (t, J = 7.8 Hz, 1 H, ArH), 7.06 (t, J = 6.8 Hz, 1 H, ArH), 7.17 (t, J = 7.8 Hz, 1 H, ArH), 7.24-7.36 (m, 2 H, ArH + CHOC=O), 7.55 (d, J = 8.3 Hz, 1 H, ArH), 7.76 (d, J = 4.8 Hz, 1 H, ArH), 8.11-8.14 (m, 1 H, ArH), 9.05 (d, J = 4.8 Hz, 1 H, ArH), 9.17 (s, 1 H, ArH). ¹³C NMR: δ = 27.0 (3 CH₃), 27.9 (CH₃), 38.6 (C), 74.4 (CH), 83.4 (C), 109.9 (CH), 117.7 (CH), 122.0 (CH), 124.8 (CH), 125.6 (C), 126.8 (CH), 128.6 (CH), 128.7 (CH), 130.8 (CH), 131.4 (C), 132.5 (C), 133.8 (CH), 135.6 (C), 140.7 (C), 145.6 (CH), 146.6 (C), 151.1 (CH), 165.1 (C), 175.7 (C). Anal. Calcd for C₂₆H₂₄BrN₅O₃ (534.42): C, 58.44; H 4.53; N, 13.10. Found: C, 58.79; H, 4.84; N, 13.37. Compound Z-3: white solid, mp 169-170 °C. ¹H NMR: δ = 1.25 (s, 9 H, 3 CH₃), 3.55 (s, 3 H, NCH₃), 7.25-7.47 (m, 3 H, ArH), 7.64-7.76 (m, 3 H, ArH), 8.64 (d, J = 4.9 Hz, 1 H, ArH). ¹³C NMR: δ = 26.8 (3 CH₃), 29.4 (CH₃), 39.3 (C), 116.8 (CH), 124.5 (C), 127.4 (C), 127.9 (CH), 130.0 (C), 131.8 (C), 132.0 (CH), 133.7 (CH), 134.3 (C), 134.4 (CH), 135.8 (C), 143.9 (CH), 149.3 (CH), 165.4 (C), 176.4 (C). Anal. Calcd for C₂₀H₁₉BrN₂O₃ (415.29): C, 57.84; H, 4.61; N, 6.75. Found: C, 57.61; H, 4.54; N, 6.47.