First Total Synthesis of (±)-Powelline

Abstract

The first total synthesis of (±)-powelline is reported in 10% overall yield over eight steps using an intramolecular oxidative phenolic coupling reaction as the key reaction.

Key words

Amaryllidaceae alkaloids - powelline - ortho-formylation - intramolecular Michael cyclization - phenolic oxidation

References and Notes

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13

Analytical and Spectroscopic Data of Selected Compounds:
Compound 9: white solid; mp 147-149 ˚C. ^¹H NMR (300 MHz, DMSO-d ₆): δ = 9.20 (br s, 1 H), 6.94 (d, J = 8.4 Hz, 2 H), 6.71 (d, J = 7.9 Hz, 1 H), 6.63 (d, J = 8.4 Hz, 2 H), 6.52 (d, J = 7.9 Hz, 1 H), 5.94 (s, 2 H), 3.82 (s, 3 H), 3.56 (s, 2 H), 3.41 (br s, 1 H), 2.54-2.63 (m, 4 H). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 155.44, 147.90, 141.40, 136.26, 130.49, 129.45, 125.94, 122.06, 115.07, 102.30, 100.89, 59.47, 50.51, 47.68, 35.00. HRMS: m/z [M⁺] calcd for C₁₇H₁₉NO₄: 301.1314; found: 301.1302.
Compound 10: colorless oil. ^¹H NMR (300 MHz, CDCl₃):
δ = 6.98-7.02 (m, 2 H), 6.74-6.80 (m, 2 H), 6.51-6.53 (m, 2 H), 5.94 (d, J = 3.0 Hz, 2 H), 5.20 (br s, 1 H), 4.63 (s, 1 H), 4.42 (s, 1 H), 4.01 (d, J = 7.8 Hz, 3 H), 3.41-3.50 (m, 2 H),
2.70-2.84 (m, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 155.04, 154.84, 150.02, 149.85, 142.43, 142.12, 136.59, 136.53, 130.63, 130.35, 130.24, 129.91, 123.83, 122.10, 120.70, 119.93, 116.01, 115.83, 103.24, 102.95, 101.62, 101.52, 60.04, 59.90, 48.63, 44.59, 34.75, 32.38. HRMS: m/z [M⁺] calcd for C₁₉H₁₈F₃NO₅: 397.1137; found: 397.1125.
Compound 11: yellow crystals; mp 142-144 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 6.94 (m, 1 H), 6.81 (m, 1 H),
6.21-6.27 (m, 3 H), 5.90 (s, 2 H), 4.91 (d, J = 5.7 Hz, 2 H), 4.03 (d, J = 8.0 Hz, 3 H), 3.88 (m, 2 H), 2.36 (t, J = 6.3 Hz, 2 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 185.65, 185.43, 157.95 (m), 153.18, 152.95, 149.36, 149.32, 141.94, 141.05, 137.25, 136.06, 130.97, 130.46, 127.49, 127.48, 122.57, 122.16, 118.74, 118.55, 114.92, 114.74, 104.94, 104.39, 102.08, 101.73, 60.21, 49.16, 48.71, 45.65 (d, J = 3.4 Hz), 44.64, 40.47 (d, J = 3.4 Hz), 40.00, 35.47, 33.90. HRMS:
m/z [M⁺] calcd for C₁₉H₁₆F₃NO₅: 395.0981; found: 395.0968. Compound 12: white crystals; mp 175-177 ˚C (lit.^¹6 mp 177-178 ˚C). ^¹H NMR (300 MHz, DMSO-d ₆): δ = 7.86 (d, J = 10.3 Hz, 1 H), 6.93 (s, 1 H), 5.90-5.94 (m, 3 H), 4.03 (d, J = 17.3 Hz, 1 H), 3.88 (s, 3 H), 3.64 (d, J = 17.3 Hz, 1 H), 3.46 (m, 1 H), 3.36 (m, 1 H), 2.81 (m, 1 H), 2.48 (m, 1 H), 2.30 (m, 1 H), 2.13 (m, 2 H). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 197.93, 150.97, 147.91, 140.49, 137.45, 133.57, 127.89, 117.62, 100.71, 97.34, 67.96, 59.00, 57.41, 53.69, 44.48, 44.48, 39.78. HRMS: m/z [M⁺] calcd for C₁₇H₁₇NO₄: 299.1158; found: 299.1151.
Compound 13: white crystals; mp 102-104 ˚C. ^¹H NMR (600 MHz, DMSO-d ₆): δ = 6.67 (s, 1 H), 6.38 (dd, J = 10.2, 2.1 Hz, 1 H), 5.88 (ABq, 2 H), 5.61 (d, J = 10.2 Hz, 1 H), 4.90 (br s, 1 H), 4.16 (m, 1 H), 4.06 (d, J = 17.3 Hz, 1 H), 3.86 (s, 3 H), 3.62 (d, J = 17.3 Hz, 1 H), 3.22 (m, 1 H), 3.02 (dd, J = 13.2, 3.4 Hz, 1 H), 2.77 (m, 1 H), 1.98 (m, 1 H), 1.92 (m, 1 H), 1.82 (m, 1 H), 1.42 (m, 1 H). ^¹³C NMR (75 MHz, DMSO-d ₆): δ = 147.53, 140.30, 139.77, 133.12, 132.69, 127.65, 117.03, 100.42, 97.14, 65.88, 65.82, 58.86, 57.74, 52.70, 44.73, 43.91, 34.37. HRMS: m/z [M⁺] calcd for C₁₇H₁₉NO₄: 301.1314; found: 301.1316. The NOESY experiment was recorded on a Bruker Avance DPX-600 MHz spectrometer at 300.3 K with F2 acquisition parameters D1 = 2.00 s and D8 = 0.89 s using DMSO-d ₆ as solvent.
Compound 2: white crystals; mp 165-167 ˚C (dec.). ^¹H NMR (300 MHz, CDCl₃): δ = 6.56 (s, 1 H), 6.52 (d, J = 10.0 Hz, 1 H), 5.95 (dd, J = 10.0, 5.1 Hz, 1 H), 5.85 (ABq, 2 H), 4.35 (m, 1 H), 4.28 (d, J = 17.3 Hz, 1 H), 3.97 (s, 3 H), 3.85 (d, J = 17.3 Hz, 1 H), 3.43 (m, 2 H), 2.90 (m, 1 H), 2.15 (m, 2 H), 1.94 (m, 1 H), 1.76 (m, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 148.23, 140.93, 138.83, 133.45, 131.68, 127.64, 116.42, 100.62, 96.79, 63.72, 62.62, 59.14, 58.40, 53.56, 44.22, 43.68, 32.39. HRMS: m/z [M⁺] calcd for C₁₇H₁₉NO₄: 301.1314; found: 301.1307.