Synlett 2019; 30(16): 1899-1903
DOI: 10.1055/s-0039-1690131
letter
© Georg Thieme Verlag Stuttgart · New York

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

Matthew J. Palframan
a  School of Chemistry, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK   Email: gp@nottingham.ac.uk
,
Krishna K. Bandi
b  Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YG, UK
,
James G. C. Hamilton
b  Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YG, UK
,
Gerald Pattenden
a  School of Chemistry, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK   Email: gp@nottingham.ac.uk
› Author Affiliations
Further Information

Publication History

Received: 04 June 2019

Accepted after revision: 15 July 2019

Publication Date:
13 August 2019 (online)

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.

Supporting Information

 
  • References and Notes

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    • Two homosesquiterpene structures have previously been characterised as pheromones in other populations of sandfly from different regions of Brazil. See:
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  • 11 For a recent perspective on the role of verticillenes in the biosynthesis of the taxanes and the phomactins, see: Palframan MJ, Pattenden G. Nat. Prod. Rep. 2019; 36: 108
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  • 17 Further studies are underway to elucidate whether a one-step transfer of the proton at C7 to C11 occurs or if two discrete steps are involved.
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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.