Enantiospecific Total Synthesis of TAN1251C and TAN1251D

Abstract

An enantiospecific total synthesis of TAN1251C and TAN1251D has been achieved. An aromatic oxidation reaction of a secondary amine, which is prepared from two molecules of l-tyrosine derivatives, with hypervalent iodine reagent gave a spiro­cyclic product as a key intermediate for the synthesis of TAN1251C and D.

Key words

TAN1251 alkaloid - total synthesis - aromatic oxidations - hypervalent iodine - spiro cyclization

References

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9

Spectroscopic data of compound 14: white solid; mp 129-130 °C; [α]_D -163.6 (c 1.40, CHCl₃). ¹H NMR (CDCl₃): δ = 2.01 (1 H, dd, J = 3.8, 13.5 Hz), 2.28 (1 H, dd, J = 2.8, 13.5 Hz), 2.71 (1 H, dd, J = 8.9, 14.7 Hz), 2.99 (3 H, s), 3.18 (1 H, d, J = 12.2 Hz), 3.41-3.50 (2 H, m), 3.85-3.90 (2 H, m), 5.01 (2 H, s), 6.19 (1 H, dd, J = 1.8, 10.1 Hz), 6.31 (1 H, dd, J = 1.8, 10.1 Hz), 6.75 (1 H, dd, J = 3.1, 10.1 Hz), 6.85 (2 H, d, J = 8.6 Hz), 6.90 (1 H, dd, J = 3.1, 10.1 Hz), 7.06 (2 H, d, J = 8.6 Hz), 7.31-7.43 (5 H, m). ¹³C NMR (CDCl₃): δ = 33.5, 35.9, 44.9, 59.3, 61.6, 63.2, 69.7, 70.4, 114.4, 124.4, 126.7, 127.2, 127.7, 128.3, 129.9, 132.4, 136.9, 149.0, 150.8, 157.0, 169.7, 185.1. IR (KBr): 2970, 1668, 1650, 1510, 1452, 1396, 1310, 1235, 1178, 1095, 1005, 864 cm^-1. HRMS: m/z calcd for C₂₆H₂₆N₂O₃: 414.1943; found: 414.1940. Anal. Calcd for C₂₆H₂₆N₂O₃: C, 75.34; H, 6.32; N, 6.76. Found: C, 75.37; H, 6.48; N, 6.71.

10

In the aromatic oxidation, PIFA instead of PhI(OAc)₂ gave the dienone 14 in only 15% yield.

12

Spectroscopic data of compound 15: white solid; mp 134-135 °C; [α]_D -52.6 (c 1.23, CHCl₃). ¹H NMR (CDCl₃): δ = 1.91 (1 H, dd, J = 4.3, 12.9 Hz), 1.98-2.01 (3 H, m), 2.21 (1 H, dd, J = 2.3, 12.9 Hz), 2.26-2.55 (5 H, m), 2.81 (1 H, dd, J = 5.4, 14.2 Hz), 2.92 (3 H, s), 3.19 (1 H, d, J = 10.7 Hz), 3.39-3.50 (2 H, m), 3.77 (1 H, br m), 3.99 (1 H, t, J = 6.3 Hz), 5.03 (2 H, s), 6.89 (2 H, d, J = 8.7 Hz), 7.32 (2 H, d, J = 8.7 Hz), 7.29-7.44 (5H, m). ¹³C NMR (CDCl₃): δ = 29.5, 33.1, 35.9, 37.4, 38.3, 39.0, 39.7, 42.0, 59.5, 61.8, 66.0, 69.8, 70.4, 114.4, 127.3, 127.7, 128.3, 129.9, 133.5, 137.0, 156.9, 170.5, 209.5. IR (KBr): 2955, 2868, 1715, 1650, 1510, 1456, 1392, 1310, 1235, 1176, 1024, 826 cm^-1. HRMS: m/z calcd for C₂₆H₃₀N₂O₃: 418.2256; found: 418.2245. Anal. Calcd for C₂₆H₃₀N₂O₃: C, 74.61; H, 7.22; N, 6.69. Found: C, 74.64; H, 7.24; N, 6.64.

13

Spectroscopic data of TAN1251D: colorless oil; [α]_D +24.7 (c 0.20, MeOH). ¹H NMR (CDCl₃): δ = 1.67 (1 H, dd, J = 5.8, 13.7 Hz), 1.73 (3 H, s), 1.79 (3 H, s), 1.86 (1 H, d, J = 13.7 Hz), 1.98-2.03 (2 H, m), 2.14 (3 H, s), 2.18-2.27 (2 H, m), 2.33-2.59 (5 H, m), 2.63-2.68 (2 H, m), 2.98-3.05 (2 H, m), 3.18-3.35 (3 H, m), 4.47 (2 H, d, J = 6.6 Hz), 5.46-5.51 (1 H, m), 6.82 (2 H, d, J = 8.6 Hz), 7.07 (2 H, d, J = 8.6 Hz). ¹³C NMR (CDCl₃): δ = 18.2, 25.8, 33.0, 33.2, 37.9, 39.2, 39.5, 41.3, 42.4, 52.2, 61.2, 61.8, 64.7, 65.0, 65.7, 114.6, 119.7, 129.7, 131.8, 138.0, 157.4, 210.8. IR (thin film): 2925, 2853, 1719, 1611, 1520, 1458, 1377, 1297, 1238, 1010, 772 cm^-1. HRMS: m/z calcd for C₂₄H₃₄N₂O₂: 382.2620; found: 382.2648.

14

Spectroscopic data of TAN1251C: colorless oil; [α]_D +23.0 (c 0.76, MeOH). ¹H NMR (CDCl₃): δ = 1.74 (3 H, s), 1.79 (3 H, s), 1.81-1.84 (1 H, m), 1.88 (1 H, dd, J = 5.1, 13.0 Hz), 1.98 (1 H, ddd, J = 4.6, 10.2, 13.0 Hz), 2.51 (3 H, s), 2.16-2.64 (7 H, m), 2.79 (1 H, dd, J = 1.3, 11.5 Hz), 3.20 (1 H, dd, J = 3.0, 11.5 Hz), 3.21 (2 H, s), 3.39-3.44 (1 H, m), 4.48 (2 H, d, J = 6.8 Hz), 5.24 (1 H, s), 5.47-5.52 (1 H, m), 6.83 (2 H, d, J = 8.6 Hz), 7.08 (2 H, d, J = 8.6 Hz). ¹³C NMR (CDCl₃): δ = 18.2, 25.8, 34.6, 37.3, 37.8, 39.5, 40.3, 41.4, 42.9, 52.2, 59.0, 64.7, 71.4, 114.4, 119.9, 127.8, 128.2, 129.8, 131.9, 138.0, 157.1, 211.6. IR (thin film): 3415, 2928, 2865, 1716, 1678, 1642, 1610, 1508, 1445, 1376, 1298, 1234, 1174, 1112, 1057 cm^-1. HRMS: m/z calcd for C₂₄H₃₂N₂O₂: 380.2464; found: 380.2453.