First Total Synthesis and Assignment of the Absolute Configuration of the Neuronal Cell Protecting Alkaloid Carbazomadurin B

Abstract

Using a palladium-catalyzed approach, the first enantio­selective synthesis of the neuronal cell protecting agent carbazomadurin B is described and its absolute configuration is assigned.

Key words

alkaloids - aminations - cross-coupling - cyclizations - palladium

References and Notes

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1

Transition Metal Complexes in Organic Synthesis, Part 78. For part 77, see ref. 4h.

7

(S)-(-)-2-Methyl-1-butanol (99% purity) from Aldrich.

18

Carbazomadurin B (1b): light-yellow crystals, mp 165 °C (dec.). [α]_D ²⁴ +13.0 (c 0.05, MeOH); [α]_D ¹⁹ +16.8 (c 0.37, MeOH). UV (MeOH): λ = 237, 249 (sh), 289 (sh), 299, 347, 356 nm. UV (MeOH, NaOH): λ = 236, 257, 303, 363 nm. IR (KBr): ν = 3477, 3431, 2959, 2929, 2873, 1618, 1584, 1524, 1426, 1377, 1269, 1168, 1075, 972, 819 cm^-1. ¹H NMR (500 MHz, acetone-d ₆): δ = 0.94 (t, J = 7.3 Hz, 3 H), 0.99 (dd, J = 6.3, 5.4 Hz, 3 H), 1.22-1.28 (m, 1 H), 1.42-1.53 (m, 3 H), 1.57 (d, J = 1.1 Hz, 3 H), 1.67-1.73 (m, 1 H), 2.27 (s, 3 H), 2.30-2.42 (m, 2 H), 3.93 (br s, 1 H), 5.02 (s, 2 H), 6.44 (s, 1 H), 6.73 (d, J = 7.7 Hz, 1 H), 6.92 (d, J = 7.7 Hz, 1 H), 7.60 (s, 1 H), 7.79 (br s, 1 H), 8.40 (br s, 1 H), 8.87 (br s, 1 H). ¹³C NMR and DEPT (125 MHz, acetone-d ₆): δ = 11.36 (CH₃), 13.22 (CH₃), 17.65 (CH₃), 19.11 (CH₃), 29.70 (CH₂), 34.65 (CH), 35.30 (CH₂), 37.14 (CH₂), 63.49 (CH₂), 106.70 (CH), 109.34 (CH), 118.61 (CH), 120.12 (CH), 121.14 (C), 122.08 (C), 122.14 (C), 123.29 (C), 128.13 (C), 130.21 (C), 133.37 (C), 142.47 (C), 142.62 (C), 149.63 (C). MS (EI): m/z (%) = 367 (73) [M⁺], 366 (10), 365 (27), 351 (100), 349 (11). HRMS: m/z calcd for C₂₃H₂₉NO₃ [M⁺]: 367.2147; found: 367.2157. Anal. Calcd for C₂₃H₂₉NO₃: C, 75.17; H, 7.95; N, 3.81. Found: C, 75.12; H, 7.99; N, 3.57.