Download PDF
Synlett 2012; 23(9): 1358-1360
DOI: 10.1055/s-0031-1290956
letter
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of (±)-Moluccanic Acid Methyl Ester

Dmitry B. Ushakov
a   Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
,
Aruna Raja
b   Abteilung Chemische Biologie, Helmholtz-Zentrum für Infektionsforschung, Inhoffenstr. 7, 38124 Braunschweig, Germany, Fax: +49(7071)295137   Email: martin.e.maier@uni-tuebingen.de
,
Raimo Franke
b   Abteilung Chemische Biologie, Helmholtz-Zentrum für Infektionsforschung, Inhoffenstr. 7, 38124 Braunschweig, Germany, Fax: +49(7071)295137   Email: martin.e.maier@uni-tuebingen.de
,
Florenz Sasse
b   Abteilung Chemische Biologie, Helmholtz-Zentrum für Infektionsforschung, Inhoffenstr. 7, 38124 Braunschweig, Germany, Fax: +49(7071)295137   Email: martin.e.maier@uni-tuebingen.de
,
Martin E. Maier*
a   Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany
› Author Affiliations
Further Information

Publication History

Received: 17 February 2012

Accepted after revision: 12 March 2012

Publication Date:
10 May 2012 (online)

    Permissions and Reprints All articles of this category


Abstract

An effective total synthesis of the trinorditerpenoid moluccanic acid methyl ester has been achieved. The synthesis features a Robinson annulation, followed by aromatization to construct the aromatic ring and Baeyer–Villiger oxidation of the A ring to finish the target molecule.

Key words

aromatization - moluccanic acid - diterpenoids - Baeyer–Villiger oxidation - Robinson annulation

Supporting Information

    for this article is available online at http://www.thieme-connect.com/ejournals/toc/synlett.
  • Supporting Information
 

  • References and Notes

  • 1 Liu H, Di Y, Yang J, Teng F, Lu Y, Ni W, Chen C, Hao X. Tetrahedron Lett. 2008; 49: 5150
    Crossref
  • 2 Ramachandran S, Newman MS. Org. Synth. 1961; 41: 38 ; Org. Synth., Coll. Vol. 5, 1973, 486

      • For preparations of the Wieland–Miescher ketone with high ee value, see:
    • 3a Bradshaw B, Etxebarria-Jardí G, Bonjoch J, Viózquez SF, Guillena G, Nájera C. Org. Synth. 2011; 88: 330
    • 3b Zhou P, Zhang L, Luo S, Cheng J.-P. J. Org. Chem. 2012; 77: 2526
      Crossref
  • 4 Pemp A, Seifert K. Tetrahedron Lett. 1997; 38: 2081
    Crossref

      • See also:
    • 5a Assefa H, Nimrod A, Walker L, Sindelar R. Bioorg. Med. Chem. Lett. 2001; 11: 1619
      Crossref
    • 5b Fernández-Mateos A, Teijón PH, Clemente RR, González RR, González FS. Synlett 2007; 2718
      Article in Thieme Connect
    • 5c Snitman DL, Tsai M.-Y, Watt DS, Edwards CL, Stotter PL. J. Org. Chem. 1979; 44: 2838
      Crossref
    • 5d Jung ME, Duclos BA. Tetrahedron 2006; 62: 9321
      Crossref
  • 6 For a similar route to tricyclic enone 6, see: Yajima A, Mori K. Eur. J. Org. Chem. 2000; 4079

      • For some representative methods, see:
    • 7a Burns NZ, Krylova IN, Hannoush RN, Baran PS. J. Am. Chem. Soc. 2009; 131: 9172
      Crossref
    • 7b Chen K, Liu C, Deng L, Xu G. Steroids 2010; 75: 513
      Crossref
    • 7c Izawa Y, Pun D, Stahl SS. Science 2011; 333: 209
  • 8 Bhatt S, Nayak SK. Tetrahedron Lett. 2006; 47: 8395
    Crossref
  • 9 Rao PN, Cessac JW, Kim HK. Steroids 1994; 59: 621
    Crossref
  • 10 For a solution to this problem in a related structure, see: Kim MB, Shaw JT. Org. Lett. 2010; 12: 3324
    Crossref
  • 11 For a recent example of a Baeyer–Villiger oxidation on a tricyclic ketone, see: Yokoe H, Mitsuhashi C, Matsuoka Y, Yoshimura T, Yoshida M, Shishido K. J. Am. Chem. Soc. 2011; 133: 8854
    Crossref

      • For some reviews, see:
    • 12a Renz M, Meunier B. Eur. J. Org. Chem. 1999; 737
    • 12b ten Brink GJ, Arends IW. C. E, Sheldon RA. Chem. Rev. 2004; 104: 4105
      Crossref
  • 13 Maitraie D, Hung C.-F, Tu H.-Y, Liou Y.-T, Wei B.-L, Yang S.-C, Wang J.-P, Lin C.-N. Bioorg. Med. Chem. 2009; 17: 2785
    Crossref
  • 14 Methyl 3-[(1S,2R)-7-Hydroxy-2-(2-hydroxypropan-2-yl)-1-methyl-1,2,3,4-tetrahydronaphthalen-1-yl]-propanoate (15) and Methyl 3-[(1S,2S)-7-Hydroxy-1-methyl-2-(prop-1-en-2-yl)-1,2,3,4-tetrahydro-naphthalen-1-yl]propanoate (2) PTSA monohydrate (2.03 g, 10.7 mmol) was added in one portion to a stirred solution of lactone 14 (520 mg, 1.34 mmol) in MeOH (10 mL) at r.t. The resulting solution was stirred overnight, treated with sat. NaHCO3 solution (30 mL) and extracted with EtOAc (3 × 30 mL). The combined organic layers were washed with sat. NaCl solution (30 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (PE–EtOAc = 9:1 to 4:1) to give the two esters 15 (320 mg, 60%) and 2 (160 mg, 30%) as colorless oils. Ester 2: Rf = 0.33 (PE–EtOAc = 4:1). 1H NMR (400 MHz, CDCl3): δ = 1.19 (s, 3 H, 1-CH3), 1.77 (s, 3 H, CH 3C=CH2), 1.56 (s, 3 H, 5-CH3), 1.80–2.15 (m, 5 H, 2′-H, 2 × 3′-H, 2 × 3-H), 2.21–2.29 (m, 1 H, 2′-H), 2.38 (dd, J = 11.4, 3.0 Hz, 1 H, 2-H), 2.68–2.75 (m, 2 H, 2 × 4-H), 3.61 (s, 3 H, OCH3), 4.69 (br s, 1 H, =CH2), 4.94 (br s, 1 H, =CH2), 6.61 (dd, J = 8.1, 2.5 Hz, 1 H, 6-H), 6.75 (d, J = 2.5 Hz, 1 H, 5-H), 6.89 (d, J = 8.1 Hz, 1 H, 8-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 22.8 (CH3C=CH2), 24.7 (C-3), 27.8 (1-CH3), 29.5 (C-2′, C-4), 34.6 (C-3′), 41.1 (C-1), 47.0 (C-2), 51.7 (OCH3), 112.9 (C-8), 113.3 (C-6), 114.3 (C=CH2), 129.1 (C-4a), 130.1 (C-5), 144.5 (C-8a), 146.6 (C=CH2), 154.0 (C-7), 175.0 (ester). ESI-HRMS: m/z calcd for C18H24O3Na [M + Na]+: 311.161766; found: 311.161980. Ester 15: Rf = 0.10 (PE–EtOAc = 4:1). 1H NMR (400 MHz, CDCl3): δ = 1.29 [s, 3H, C(CH3)2], 1.35 (s, 3 H, 1-CH3), 1.47 [s, 3 H, C(CH3)2], 1.50–1.76 (m, 3 H, 2 × 3-H, 2-H), 1.92–2.10 (m, 3 H, 2 × 3′-H, 2′-H), 2.17 (s, 1 H, OH), 2.56–2.69 (m, 2 H, 2′-H, 4-H), 2.82–2.88 (m, 1 H, 4-H), 3.60 (s, 3 H, OCH3), 6.58 (dd, J = 8.3, 2.5 Hz, 1 H, 6-H), 6.79 (d, J = 2.3 Hz, 1 H, 8-H), 6.85 (d, J = 8.3 Hz, 1 H, 5-H) ppm. 13C NMR (100 MHz, CDCl3): δ = 24.5 (C-3), 26.8 [C(CH3)2], 27.2 (1-CH3), 29.6 (C-4), 30.7 [C(CH3)2], 33.2 (C-2′), 36.6 (C-3′), 43.4 (C-1), 48.7 (C-2), 51.8 (OCH3), 75.5 [C(CH3)2], 112.9 (C-6), 113.2 (C-8), 129.6 (C-4a), 129.8 (C-5), 146.4 (C-8a), 154.4 (C-7), 176.3 (C-1′) ppm. ESI-HRMS: m/z calcd for C18H26O4Na [M + Na]+: 329.172330; found: 329.172482
  • 15 MTT = 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide
    • 16a Staton CA, Stribbling SM, Tazzyman S, Hughes R, Brown NJ, Lewis CE. Int. J. Exp. Pathol. 2004; 85: 233
      Crossref
    • 16b Vintonyak VV, Calà M, Lay F, Kunze B, Sasse F, Maier ME. Chem.–Eur. J. 2008; 14: 3709
  • 17 Abassi YA, Xi B, Zhang W, Ye P, Kirstein SL, Gaylord MR, Feinstein SC, Wang X, Xu X. Chem. Biol. 2009; 16: 712
    Crossref