First Total Synthesis of (-)-1(10),5-Germacradien-4-ol

Abstract

This paper presents a total synthesis of (-)-1(10),5-germacradien-4-ol, a constituent of the needles of Scots pine and of the defence secretion from the larvae of the pine sawfly. The synthesis uses a strategy based on an intramolecular alkylation to form an unsaturated monocyclic 10-membered ring.

Key words

germacrane terpenoids - intramolecular alkylation - stereoselective synthesis

References

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• 4a Two numbering systems of 1 occur in the literature. We have used the germacrane numbering system described in: Connolly JD. Hill RA. Dictionary of Terpenoids   Chapman & Hall; London: 1991. 
• 4b

  Another system of numbering 1 is used e.g. in refs. 3,6,8,9,10,21,23.

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2

PHERODIP, Pine sawfly pheromones for sustainable management of European forests; European Community contacts, no. FAIR1-CT95-0339. Final report.

15

Isolated yield of homogeneous substances. All new compounds showed satisfactory spectroscopic data based on data from ¹H and ¹³C NMR, IR and MS.

17

Attempted removal of the benzyl group with H₂/Pd-C in MeOH was inefficient, whereas migration of the silyl group was observed in THF.

22

Data of 2: IR (neat, KBr): 2960, 2930, 2870, 1690, 1650, 1625, 1385, 1370, 1155, 1105, 990 cm^-1; ¹H NMR* (250.13 MHz, CDCl₃): δ 6.08 (dd, J = 16, 10 Hz, 1 H), 6.06 (d, J = 16 Hz, 1 H), 5.00-5.08 (m, 1 H), 2.65 (m, 1 H), 2.05-2.50 (m, 6 H), 1.91 (m, 1 H), 1.50-1.76 (m, 2 H), 1.49 (s, br, 3 H), 0.90 (d, J = 6.8 Hz, 3 H), 0.84 (d, J = 6.8 Hz, 3 H); significant shifts of minor stable conformer, or 5Z-isomer: δ 6.64 (dd,
J = 16, 10 Hz, 1 H), 5.98 (d, br, J = 16 Hz, 1 H), 5.30 (m,
1 H), 1.30 (s, br, 3 H), 0.95 (d, J = 6.7 Hz, 3 H), 0.88 (d, J = 6.6 Hz, 3 H); ¹³C NMR (62.9 MHz, CDCl₃): δ 202.4, 149.7, 136.8, 135.4, 129.0, 52.8, 40.9, 40.4, 32.3, 28.0, 25.4, 20.8, 19.5, 15.6; minor stable conformer, or 5Z-isomer: δ 201.7, 159.9, 141.1, 128.4, 126.6, 49.9, 38.9, 35.6, 34.4, 30.9, 25.4, 20.8, 20.7, 18.9; MS (EI, ion trap) m/z (rel. int.): 206 (M⁺, 40), 189(15), 163(35), 136(100), 121(35), 107(40), 93(80), 79(70), 67(45); MS (CI, ion trap, CH₃CN as ionisation gas) m/z (rel. int.): 207 (M + H⁺, 75), 189(100).
*Due to the fact that this is a mixture of two stable conformers, or 5E/5Z isomers, the ¹H NMR characterisation is still pending.