Investigation of the Biomimetic Synthesis of Emindole SB Using a Fluorinated Polyene Cyclisation Precursor

Abstract

The synthesis and Lewis acid initiated cationic cyclization of a fluorine-containing triene-epoxide has been explored in an attempt to construct the pentacyclic core of emindole SB in a manner that mimics its putative biosynthetic pathway.

Key words

indole - alkaloid - biomimetic synthesis - fluorine

References

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14

Careful analysis of the ¹⁹F NMR, ¹H NMR and ¹³C NMR spectra revealed that pentacyclic alcohol 2b was produced from the Lewis acid-mediated cyclisation of the vinyl epoxide 1b. The ³ J _HF of 34 Hz and 15 Hz between fluorine and the protons of the methylene group immediately adjacent to the carbon bearing fluorine are diagnostic.

15

Spectroscopic data for alcohol 2b: IR (CHCl₃): ν_max = 2931, 1602, 1452, 1123, 908 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 7.56 (1 H, d, J = 8.2 Hz), 7.41 (1 H, d, J = 7.2 Hz), 7.27-7.02 (2 H, m, CH), 5.67 (1 H, dd, J = 10.7, 17.5 Hz), 5.27 (1 H, d, J = 10.7 Hz), 5.16 (1 H, d, J = 17.5 Hz), 3.39 (1 H, dd, J = 11.5, 4.6 Hz), 3.01 (1 H, dd, ² J _HH = 15.2, ³ J _HF = 34.0 Hz), 2.82 (1 H, dd, ² J _HH = 15.2, ³ J _HF = 15.0 Hz), 2.30-2.21 (1 H, m), 2.15-2.05 (1 H, m), 2.00-1.50 (8 H, m), 1.28 (3 H, d, ⁴ J _HF = 2.0 Hz), 1.13 (3 H, s), 1.04 (3 H, s), 0.96 (9 H, s), 0.76 (3 H, s), 0.62 (3 H, s). ¹³C NMR (125 MHz, CDCl₃): δ = 156.2 (C), 148.4 (CH), 145.5 (C), 128.0 (C), 120.0 (CH), 119.8 (CH), 118.5 (C), 117.9 (CH), 115.7 (CH), 115.2 (CH₂), 75.9 (CH), 52.2 (C, d, ² J _CF = 22 Hz), 46.3 (C), 43.5 (CH, d, ³ J _CF = 6 Hz), 41.0 (C, d, ² J _CF = 19 Hz), 31.3 (CH₂, d, ³ J _CF = 6 Hz), 27.6 (CH₂, d, ² J _CF = 26 Hz), 27.3 (3 × CH₃), 26.4 (CH₃), 24.9 (CH₂), 24.6 (CH₃), 20.6 (C), 19.7 (CH₂), 19.3 (CH₂), 18.2 (CH₃, d, ³ J _CF = 5 Hz), 10.5 (CH₃), 0.9 (CH₃), 0.6 (CH₃). ¹⁹F NMR (282 MHz, CDCl₃): δ = -148 (dd, ³ J _FH = 34, 15 Hz).