A Brief Total Synthesis of Eupolauramine

Véronique Rys; Axel Couture; Eric Deniau; Stéphane Lebrun; Pierre Grandclaudon

doi:10.1055/s-2004-830889

LETTER

A Brief Total Synthesis of Eupolauramine

Véronique Rys, Axel Couture*, Eric Deniau, Stéphane Lebrun, Pierre Grandclaudon
Laboratoire de Chimie Organique Physique, UMR 8009 ‘Laboratoire de Chimie Organique et Macromoléculaire’, Université des Sciences et Technologies de Lille, Bâtiment C3(2), 59655 Villeneuve d’Ascq Cédex, France
Fax: +33(3)20336119; e-Mail: axel.couture@univ-lille1.fr;

Abstract

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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.

Key words

alkaloids - carbanions - enols - ring closure - total synthesis

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References

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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.