Acid-Catalysed Rearrangement of the Sandfly Pheromone Sobralene to Verticillenes, Consolidating its Relationship inter alia to the Taxanes and Phomactins

Abstract

The sex-aggregation pheromone sobralene produced by the sandfly Lutzomyia longipalpis is isomerised to verticillenes in the presence of mild acid, thereby providing credence to the proposal that sobralene is a likely shunt metabolite of the taxadiene synthase cascade.

Key words

pheromone - sandfly - verticillenes - metabolite - taxadiene

• References and Notes

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• 19 Trifluoroacetic acid (1.0 μL, 0.0130 mmol) was added to a solution of 12-epi-verticillol (19, 1.20 mg, 0.00413 mmol) in C₆D₆ (0.75 mL), and the resulting solution was heated at 60 °C for 3 h. A further portion of trifluoroacetic acid (2.0 μL, 0.0260 mmol) was added, and the solution was heated for a further 2 h. The solution was cooled to room temperature and evaporated to dryness. The residue was purified by silica gel chromatography, eluting with pentane to afford endo-verticillene (0.90 mg, 80%) as a pale-yellow oil. ¹H NMR (500 MHz, C₆D₆): δ = 5.48 (1 H, br s, H13), 5.45 (1 H, d, J = 12.4 Hz, H3), 4.89 (1 H, d, J = 10.5 Hz, H7), 3.08 (1 H, br s, H11), 2.65 (1 H, ddd, J = 15.9, 11.9, 4.4 Hz, H2a), 2.49 (1 H, br m, H14a), 2.39 (1 H, m, H6a), 2.24 (1 H, dd, J = 12.6, 6.1 Hz, H9a), 2.10 (2 H, m, H9b and H5a), 1.97–1.90 (2 H, m, H5b and H6b), 1.90–1.81 (2 H, m, H2b and H14b), 1.83 (3 H, s, H18), 1.52 (3 H, s, H20), 1.45 (3 H, s, H19), 1.42 (1 H, m, H1), 1.33–1.29 (2 H, m, H10), 0.88 (3 H, s, H16), 0.81 (3 H, s, H17). ¹³C NMR (126 MHz, C₆D₆): δ = 136.9 (C12), 132.8 (C8), 132.7 (C4), 130.4 (C7), 125.1 (C3), 122.2 (C13), 42.9 (C1), 41.3 (C5), 40.0 (C9), 38.4 (C11), 36.0 C15), 34.5 (C2), 31.2 (C14), 27.4 (C17), 27.1 (C6), 24.0 (C16), 23.4 (C18), 21.9 (C10), 15.8 (C19), 15.3 (C20). GC-MS: m/z (C₂₀H₃₂ ⁺, M⁺) requires 272.2499. HRMS-EI: m/z found 272.2511.
• 20 pTSA·H₂O (1.5 mg, 0.00517 mmol) was added to a solution of 12-epi-verticillol (19, 1.5 mg, 0.00517 mmol) in C₆D₆ (0.75 mL), and the resulting solution was heated at 80 °C for 20 min. The solution was cooled to room temperature, then passed through a short plug of silica, eluting with Et₂O (1 mL), and evaporated. The residue was purified by silica gel chromatography, eluting with pentane to give the iso-phomactatriene (1.0 mg, 71%) as a pale yellow oil. ¹H NMR (500 MHz, C₆D₆): δ = 5.02 (1 H, m, H9), 4.77 (1 H, d, J = 10.3 Hz, H5), 2.60 (1 H, dt, J = 2.4, 13.2 Hz, H2a), 2.28 (1 H, m, H6a), 2.15–2.05 (3 H, m, H3a, H7a, H14a), 2.03 (2 H, d, J = 8.1 Hz, H10), 2.00–1.98 (3 H, m, H3b, H6b, H7b), 1.68–1.58 (3 H, m, H2b, H12, H14b), 1.57 (3 H, s, C4CH₃), 1.53 (3 H, s, C4CH₃), 1.42 (3 H, s, C15CH₃), 1.38 (2 H, m, H13), 0.92 (3 H, d, J = 6.9 Hz, C12CH₃), 0.90 (3 H, s, C11CH₃). ¹³C NMR (125 MHz, C₆D₆): δ = 133.3 (C15), 132.9 (C8), 132.1 (C4), 131.2 (C1), 127.8 (C5), 123.5 (C9), 43.2 (C11), 39.0 (C7), 37.9 (C3), 34.6 (C12), 34.4 (C10), 32.9 (C2), 31.3(C14), 28.0 (C13), 25.7 (C6), 20.0 (C11CH₃), 17.3 (C12CH₃), 16.9 (C8CH₃), 16.4 (C4CH3), 14.5 (C15CH₃). GC-MS: m/z (C₂₀H₃₂ ⁺, M⁺) requires 272.2499. HRMS-EI: m/z found 272.2508.