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Synlett 2002(8): 1273-1276
DOI: 10.1055/s-2002-32970
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Olof Smitt, Hans-Erik Högberg*
Chemistry, Department of Natural and Environmental Sciences, Mid Sweden University, 851 70 Sundsvall, Sweden
e-Mail: Hans-Erik.Hogberg@mh.se;
Further Information

Publication History

Received 17 June 2002
Publication Date:
25 July 2002 (online)

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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

  • 1 Wagner M. Raffa KF. Sawfly Life History Adaptations to Woody Plants   Academic Press; San Diego: 1993. 
    Google Scholar
  • 3 Bergström G. Wassgren A.-B. Birgersson G. Acta Chem. Scand.  1994,  48:  187 
    Google Scholar
  • 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. 
    Google Scholar
  • 4b

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

  • 5 Bohlmann F. Knoll K.-H. Zdero C. Mahanta PD. Grenz M. Suwita A. Ehlers D. Le Van N. Abraham W.-R. Natu AA. Phytochemistry  1977,  16:  965 
    CrossrefGoogle Scholar
  • 6 Nordin O. Hedenström E. Högberg H.-E. Acta Chem. Scand.  1999,  53:  124 
    Google Scholar
  • 7 A review of syntheses of germacranes: Minnaard AJ. Wijnberg JBPA. de Groot A. Tetrahedron  1999,  55:  2115 
    CrossrefGoogle Scholar
  • 8 Ralduglin VA. Salenko VL. Gamov NS. Titova TF. Khan VA. Pentegova VA. Chem. Nat. Compd. (Engl. Transl.)  1980,  16:  154 
    CrossrefGoogle Scholar
  • 9 Nordin O. Stereoselective Synthesis of Semiochemicals Related to Pine Sawflies., Ph.D. Thesis   Royal Institute of Technology; Stockholm: 1999. 
    Google Scholar
  • 10 nor-Me synthesis: Nevalainen M. Koskinen AMP. J. Org. Chem.  2002,  67:  1554 
    CrossrefGoogle Scholar
  • 11a Takahashi T. Nagashima T. Tsuji J. Tetrahedron Lett.  1981,  22:  1359 
    Google Scholar
  • 11b Takahashi T. Yamashita Y. Doi T. Tsuji J. J. Org. Chem.  1989,  54:  4273 
    Google Scholar
  • 12 KocieŇski PJ. Pritchard M. Wadman SN. Whitby RJ. Yeates CL. J. Chem. Soc., Perkin Trans. 1  1992,  3419 
    CrossrefGoogle Scholar
  • 13a Högberg H.-E. In Houben-Weyl   4th ed., Vol. E21a:  Helmchen G. Hoffman RW. Multzer J. Schaumann E. Thieme; Stuttgart: 1995.  p.791 
    Google Scholar
  • 13b Herrmann R. In Houben-Weyl   4th ed., Vol. E21f:  Helmchen G. Hoffman RW. Multzer J. Schaumann E. Thieme; Stuttgart: 1996. 
    Google Scholar
  • 14a Myers AG. Yang BH. Chen H. McKinstry L. Kopecky DJ. Gleason JL. J. Am. Chem. Soc.  1997,  119:  6496 
    CrossrefGoogle Scholar
  • 14b Myers AG. Yang BH. In Organic Syntheses   Vol. 77:  Hart DJ. Wiley; New York: 1999.  p.22 
    CrossrefGoogle Scholar
  • 14c Myers AG. Yang BH. Chen H. In Organic Syntheses   Vol. 77:  Hart DJ. Wiley; New York: 1999.  p.29 
    CrossrefGoogle Scholar
  • 16 Dale JA. Dull DL. Mosher HS. J. Org. Chem.  1969,  34:  2543 
    CrossrefGoogle Scholar
  • 18 Ley SV. Norman J. Griffith WP. Marsden SP. Synthesis  1994,  639 
    Article in Thieme ConnectGoogle Scholar
  • 19 Rychnovsky SD. Hoye RC. J. Am. Chem. Soc.  1994,  116:  1753 
    CrossrefGoogle Scholar
  • 20a Evans DA. Truesdale LK. Carroll GL. J. Chem. Soc., Chem. Commun.  1973,  55 
    CrossrefGoogle Scholar
  • 20b Lidy W. Sundermeyer W. Chem. Ber.  1973,  106:  587 
    CrossrefGoogle Scholar
  • 21 RCM synthesis of a nor-Me relative, a 11:1 E/Z mixture of (±)-9-tert-butyldimethylsilyloxy-8-isopropylcyclodec-4-enone: Nevalainen M. Koskinen AMP. Angew. Chem. Int. Ed.  2001,  40:  4060 
    CrossrefGoogle Scholar
  • 23 MS of 1 was in good agreement with: Joulain D. Laurent R. J. Essent. Oil Res. 1  1989,  299 
    Google Scholar
  • 24 Guanti G. Banfi L. Narisano E. Riva R. Tetrahedron Lett.  1992,  33:  2221 
    CrossrefGoogle Scholar
  • 25 Blanchette MA. Choy W. Davis JT. Essenfeld AP. Masamune S. Roush WR. Sakai T. Tetrahedron Lett.  1984,  25:  2183 
    CrossrefGoogle Scholar
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.