Transition Metals in Organic Synthesis, Part 96. [¹] First Total Synthesis of Streptoverticillin: Unambiguous Confirmation of the Absolute Configuration

Abstract

Using an iron-mediated construction of the carbazole framework, the first synthesis of streptoverticillin is described and the absolute configuration of the natural product is confirmed. The synthesis exploits a novel oxygen-mediated aromatization of tricarbonyliron-coordinated dihydrocarbazoles. Moreover, non-natural (R)-streptoverticillin is prepared for comparison.

alkaloids - carbonyl complexes - cyclization - iron - total synthesis

References and Notes

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14

Spectroscopic data for synthetic streptoverticillin (1): Light-yellow solid; mp 156-157 ˚C; [α]_D ^²0 +24.0 (c = 0.1, MeOH) (Lit.⁶ [α]_D ^²0 +18.4, c = 0.179, MeOH); UV (MeOH): λ = 220, 242, 251, 262, 283, 293, 328, 340 nm; IR (ATR): 3475, 3293, 3055, 2955, 2926, 2850, 2823, 1608, 1500, 1451, 1398, 1348, 1318, 1304, 1271, 1225, 1194, 1166, 1148, 1086, 1060, 1001, 965, 934, 888, 872, 839, 787, 743, 702, 642 cm^-¹; ^¹H NMR (500 MHz, methanol-d ₄): δ = 1.27 (d, J = 6.2 Hz, 3 H), 2.45 (s, 3 H), 3.04 (dd, J = 14.1, 6.6 Hz, 1 H), 3.13 (dd, J = 14.1, 6.9 Hz, 1 H), 3.90 (s, 3 H), 4.10 (s, 3 H), 4.15 (sext, J = 6.4 Hz, 1 H), 7.14 (t, J = 7.8 Hz, 1 H), 7.35 (t, J = 8.1 Hz, 1 H), 7.47 (d, J = 8.1 Hz, 1 H), 8.16 (d, J = 7.8 Hz, 1 H), 10.30 (br s, 1 H); ^¹³C NMR and DEPT (75 MHz, methanol-d ₄): δ = 13.32 (CH₃), 23.42 (CH₃), 39.19 (CH₂), 61.07 (CH₃), 61.57 (CH₃), 69.17 (CH), 111.79 (CH), 115.90 (C), 117.36 (C), 119.93 (CH), 123.39 (CH), 123.76 (C), 126.16 (CH), 130.30 (C), 139.14 (C), 141.84 (C), 145.50 (C), 147.80 (C); MS (EI): m/z (%) = 299 (71) [M⁺], 284 (25), 254 (100), 240 (7), 224 (8), 210 (10); HRMS: m/z calcd for C₁₈H₂₁NO₃: 299.1521; found: 299.1518.

15 Flack HD. Acta Crystallogr., Sect. A: Found. Crystallogr.  1983,  39:  876 

16

Crystal data for 6-bromostreptoverticillin (16): C₁₈H₂₀BrNO₃; crystal size: 0.49 × 0.11 × 0.11 mm^³; M = 378.26 g mol^-¹; monoclinic; space group: P2₁; λ = 0.71073 Å; a = 12.8825 (10), b = 4.8516 (4), c = 13.7636 (11) Å, β = 108.909 (4)˚; V = 813.81 (11) Å^³; Z = 2; ρ _c = 1.544 g cm^-³; µ = 2.540 mm^-¹; T = 198 (2) K; θ range = 1.56-30.00˚; reflections collected: 16453, independent: 4653 (R _int = 0.0532). The structure was solved by direct methods and refined by full-matrix least squares on F ^²; R ₁ = 0.0290, wR ₂ = 0.0586 [I > 2σ(I)]; maximal residual electron density: 0.395 e Å^-³; absolute structure (Flack parameter): χ = -0.006 (6). CCDC-835819.