Download PDF
Synlett 2006(10): 1543-1546  
DOI: 10.1055/s-2006-944190
LETTER
© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Pterosines B and C via a Photochemical Key Step

Pablo Wessig*, Janek Teubner
Institut für Chemie, Humboldt-Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany
e-Mail: Pablo.wessig@chemie.hu-berlin.de;
Further Information

Publication History

Received 12 April 2006
Publication Date:
12 June 2006 (online)

    Permissions and Reprints All articles of this category

Abstract

A total synthesis of pterosines B and C is reported. Starting with a fourfold substituted benzene derivative, the introduction of the remaining substituents is mainly based on Sonogashira couplings followed by different transformations of the ethyne moiety. The key step is a photochemical ring-closure of an α-mesyloxy ­ketone forming the 1-indanone skeleton.

Key words

total synthesis - photochemistry - arenes - ketones

    References and Notes

  • 1a Kuroyanagi M. Fukuoka M. Yoshihira K. Natori S. Chem. Pharm. Bull.  1974,  22:  723 
    CrossrefGoogle Scholar
  • 1b Yoshihira K. Fukuoka M. Kuroyanagi M. Natori S. Umeda M. Morohoshi T. Enomoto M. Saito M. Chem. Pharm. Bull.  1978,  26:  2346 
    CrossrefGoogle Scholar
  • 1c McMorris TC. Kelner MJ. Wang W. Estes LA. Montoya MA. Taetle R. J. Org. Chem.  1992,  57:  6876 
    CrossrefGoogle Scholar
  • 1d Takahashi M. Fuchino H. Sekita S. Satake M. Phytother. Res.  2004,  18:  573 
    CrossrefGoogle Scholar
  • 2 Kobayashi A. Koshimizu K. Agric. Biol. Chem.  1980,  44:  393 
    Google Scholar
  • 3 Kobayashi A. Egawa H. Koshimizu K. Mitsui T. Biol. Chem.  1975,  39:  1851 
    Google Scholar
  • 4a McMorris TC. Liu M. White R. Lloydia  1977,  40:  221 
    CrossrefGoogle Scholar
  • 4b Ng K.-ME. McMorris TC. Can. J. Chem.  1984,  62:  1945 
    CrossrefGoogle Scholar
  • 4c Sheridan H. Lemon S. Frankish N. McArdle P. Higgins T. James JP. Bhandari P. Eur. J. Med. Chem.  1990,  25:  603 
    CrossrefGoogle Scholar
  • 4d Finkielsztein LM. Alesso EN. Lantaño B. Aguirre JM. Moltrasio Iglesias GY. J. Chem. Res., Synop.  1999,  6:  406 
    CrossrefGoogle Scholar
  • 4e Finkielsztein LM. Alesso EN. Lantaño B. Aguirre JM. Moltrasio Iglesias GY. J. Chem. Res., Synop.  1999,  6:  1561 
    CrossrefGoogle Scholar
  • 4f Neeson SJ. Stevenson PJ. Tetrahedron  1989,  45:  6239 
    CrossrefGoogle Scholar
  • 4g Grigg R. Scott R. Stevenson P. J. Chem. Soc., Perkin Trans. 1  1988,  1357 
    CrossrefGoogle Scholar
  • 4h Grigg R. Scott R. Stevenson P. J. Chem. Soc., Perkin Trans. 1  1988,  1365 
    CrossrefGoogle Scholar
  • 4i Padwa A. Curtis EA. Sandanayaka VP. J. Org. Chem.  1996,  61:  73 
    CrossrefGoogle Scholar
  • 5 Wessig P. Glombitza C. Müller G. Teubner J. J. Org. Chem.  2004,  69:  7582 
    CrossrefGoogle Scholar
  • 6a Wessig P. Mühling O. Angew. Chem. Int. Ed.  2001,  40 
    CrossrefGoogle Scholar
  • 6b Wessig P. Mühling O. Helv. Chim. Acta  2003,  86:  865 
    CrossrefGoogle Scholar
  • 6c Wessig P. Mühling O. Angew. Chem. Int. Ed.  2005,  6778 
    CrossrefGoogle Scholar
  • 7 Wessig P. Schwarz J. Lindemann U. Holthausen MC. Synthesis  2001,  1258 
    Article in Thieme ConnectGoogle Scholar
  • 8 Ayer WA. McCaskill RH. Can. J. Chem.  1981,  59:  2159 
    CrossrefGoogle Scholar
  • 9a Rieke RD. Hundall PM. J. Am. Chem. Soc.  1972,  94:  7178 
    CrossrefGoogle Scholar
  • 9b Rieke RD. Bales SE. J. Am. Chem. Soc.  1974,  96:  1775 
    CrossrefGoogle Scholar
  • 10 Moffett RB. Seay PH. J. Med. Pharm. Chem.  1960,  2:  201 
    CrossrefGoogle Scholar
  • 11a Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  16:  4467 
    Google Scholar
  • 11b Negishi E.-I. Anastasia L. Chem. Rev.  2003,  103:  1979 
    Google Scholar
  • 11c Sonogashira K. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon Press; Oxford: 1991.  p.521-549  
    Google Scholar
  • 12a Backlund SJ. Zweifel G. J. Am. Chem. Soc.  1977,  99:  3184 
    CrossrefGoogle Scholar
  • 12b

    4-(Carboxymethyl)-3,5-dimethylbenzoic Acid (10).
    Compound 9 (1.00 g, 3.78 mmol) in 10 mL dry THF was cooled to 0 °C and 6.8 mL (6.8 mmol, 1.8 equiv) 1 M BH3-THF solution was dropped in slowly. After stirring at 0 °C for 2 h a mixture of 10 mL (0.02 mol, 5 equiv) 2 M NaOH and 5 mL (0.06 mol, 15 equiv) aq H2O2 solution (30%) was added. After additional stirring for 2 h further 20 mL of 1 M NaOH and 50 mL of Et2O were added. The phases were separated and the aqueous phase was extracted several times with Et2O. Then the aqueous phase was acidified to pH 1 with HCl and the product was extracted with several portions of Et2O. The combined organic phases were dried and evaporated, giving 350 mg (1.68 mmol, 44%) of 10 as a white solid; mp 285 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 2.29 (s, 6 H, 3,5-Me), 3.65 (s, 2 H, CH2), 7.59 (s, 2 H, CHarom). 13C NMR (75 MHz, DMSO-d 6): δ = 19.8 (3,5-Me), 35.2 (CH2), 128.5 (CHarom), 128.8, 137.3, 137.9 (Cq), 167.4, 171.8 (COOH). IR (KBr): 2959 (br s), 2923 (s), 2858 (s), 1718 (s), 1667 (s), 1425 (s), 1413 (s), 1303 (s), 1244 (s), 1230 (s), 1182 (m). HRMS (ESI): m/z calcd for C11H13O4 [MH+]: 209.0808. Found: 209.0809.
    Crossref
  • 13 Muraki T. Togo H. Yokoyama M. J. Org. Chem.  1999,  64:  2883 
    CrossrefPubMedGoogle Scholar
  • 14 Mizushima E. Sato K. Hayashi T. Tanaka M. Angew. Chem. Int. Ed.  2002,  114:  4563 
    Google Scholar
  • 15a Koser GF. Relenyi AG. Kalos AN. Rebrovic L. Wettach RH. J. Org. Chem.  1982,  47:  2487 
    CrossrefGoogle Scholar
  • 15b Lodaya JS. Koser GF. J. Org. Chem.  1988,  53:  210 
    CrossrefGoogle Scholar
  • 16a Bergmark WR. J. Chem. Soc., Chem. Commun.  1978,  61 
    Google Scholar
  • 16b Bergmark WR. Barnes C. Clark J. Paparian S. Marynowski S. J. Org. Chem.  1985,  50:  5612 
    Google Scholar
  • 16c Favorskii AJ. Russ. Phys. Chem. Soc.  1905,  37:  643 
    Google Scholar
  • 16d Kende AS. Org. React.  1960,  11:  261 
    Google Scholar
  • 18a Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley-Interscience; New York: 1999.  p.171 
    CrossrefGoogle Scholar
  • 18b Kosmol H. Hill F. Kerb U. Kieslich K. Tetrahedron Lett.  1970,  11:  641 
    CrossrefGoogle Scholar
  • 18c Poijärvi P. Orivanen M. Lönnberg H. Lett. Org. Chem.  2004,  1:  183 
    CrossrefGoogle Scholar
17

Irradiation of 17a and 17b.
For solvents, conditions and yields see Table [1] . The irradiation was performed in a 500 mL reactor vessel, equipped with a 150 W high-pressure mercury arc lamp (TQ 150, Heraeus) and monitored by TLC. The solvent was removed in vacuo and the residue was purified by flash chromatography.
Analytical Data for 2-(4,6-Dimethyl-3-oxo-2,3-dihydro-1 H -inden-5-yl)ethyl Acetate ( 18a).
Mp 39-41 °C. 1H NMR (300 MHz, CDCl3): δ = 2.03 (s, 3 H, CH3-acetate), 2.42 (s, 3 H, Me-Carom), 2.60-2.64 (m, 2 H, 2-CH2), 2.67 (s, 3 H, Me-Carom), 2.94-2.98 (m, 2 H, 3-CH2), 3.03 (t, J 3 = 7.7 Hz, 2 H, CH2CH2O), 4.12 (t, J 3 = 7.7 Hz, 2 H, CH2CH2O), 7.10 (s, 1 H, CHarom). 13C NMR (75 MHz, CDCl3): δ = 13.6, 21.0 (CH3-Carom), 21.1 (CH3-acetate), 24.6 (3-CH2), 27.8 (CH2CH2O), 37.1 (2-CH2), 62.7 (CH2CH2O), 125.9 (CHarom), 132.9, 133.8, 137.8, 140.1, 154.6 (Cq), 171.0 (COOR), 207.8 (RCOR).
Analytical Data for 2-{1-[(Pivaloyl)oxy]-4,6-dimethyl-3-oxo-2,3-dihydro-1 H -inden-5-yl}ethyl Pivalate ( 18b).
1H NMR (300 MHz, CDCl3): δ = 1.14, 1.17 (s, 9 H, Piv), 2.46 (s, 3H, Me-Carom), 2.51 (dd, J 3 = 3.0 Hz, J 2 = 18.8 Hz, 1 H, CH2CH), 2.68 (s, 3 H, Me-Carom), 3.03 (t, J 3 = 7.7 Hz, 2 H, CH2CH2O), 3.08 (dd, J 3 = 7.1 Hz, J 2 = 18.8 Hz, 1 H, CH2CH), 4.10 (t, J 3 = 7.7 Hz, 2 H, CH2CH2O), 6.15 (dd, J 3 = 3.0 Hz, J 3 = 7.1 Hz, 1 H, CHOPiv), 7.19 (s, 1 H, CHarom). 13C NMR (75 MHz, CDCl3): δ = 13.8, 21.3 (CH3-Carom), 27.0, 27.1 (CH3, Piv), 28.0 (CH2CH2O), 38.6, 38.6 (Cq, Piv), 44.6 (2-CH2), 62.3 (CH2CH2O), 68.5 (3-CH), 73.2 (CH2O), 125.4 (CHarom), 132.8, 136.7, 137.5, 145.1, 151.0 (Cq), 178.5, 178.6 (COOR), 202.9 (RCOR). IR (film): 2973 (s), 1717 (vs), 1599 (s), 1478 (s), 1458 (s), 1396 (s), 1281 (s), 1148 (s), 1033 (s), 1010 (s), 984 (m). HRMS (ESI): m/z calcd for C23H33O5 [MH+]: 389.2323; found: 389.2324.

19

Experimental Procedure for 3-Hydroxy-6-(2-hydroxyethyl)-5,7-dimethyl-1-indanone ( 22).
To a solution of 65 mg (0.17 mmol) 18b in 10 mL DMSO was added a mixture of 100 mL 0.01 M aq HEPES buffer solution (pH 7.5, I = 0.1 M NaCl) and 90 mg (2160 units) porcine liver esterase (EC 3.1.1.1, Sigma). The mixture was stirred 2 d at r.t. in which the reaction course was monitored by HPLC analysis (see below). After complete saponification of both ester groups the mixture was treated with 50 mL CH2Cl2, filtrated and the phases were separated. The organic phase was dried with MgSO4, evaporated and purified by FCC (CH2Cl2-MeOH, 10:1, R f = 0.39) affording 20.0 mg (90.8 mol, 54%) 22 as a white solid.
HPLC conditions: column: Eurospher 100 C-18 (Knauer), 5 µm, 250 × 4 mm; mobile phase: gradient MeOH-H2O (70:30 → 90:10) linear in 20 min, then 90:10 flow: 1 mL/min. peaks: t R(22) = 2.6 min, t R(18b) = 31.9 min.
Mp 143-145 °C. 1H NMR (300 MHz, DMSO-d 6): δ = 2.34 (dd, J 3 = 3.0 Hz, J 2 = 18.5 Hz, 1 H, CH2CH), 2.40, 2.56 (s, 3 H, Me-Carom), 2.84 (t, J 3 = 7.5 Hz, 2 H, CH2CH2OH), 2.90 (dd, J 3 = 7.0 Hz, J 2 = 18.5 Hz, 1 H, CH2CH), 3.41-3.46 (m, 2 H, CH2CH2OH), 4.78 (t, J 3 = 5.5 Hz, 1 H, CH2OH), 5.02-5.06 (m, 1 H, 3-CH), 5.57 (d, J 3 = 6.0 Hz, 1 H, OH), 7.31 (s, 1 H, CHarom). 13C NMR (75 MHz, DMSO-d 6): δ = 13.3, 21.0 (CH3-Carom), 32.1 (CH2CH2OH), 47.7 (2-CH2), 59.8 (CH2CH2OH), 65.6 (3-CH), 125.0 (CHarom), 131.5, 135.6, 137.1, 144.2, 155.6 (Cq), 204.3 (RCOR). IR (KBr): 3391 (br s), 2923 (m), 1687 (vs), 1596 (s), 1408 (m), 1326 (m), 1308 (s), 1260 (m), 1065 (s), 1025 (s), 804 (m). HRMS (ESI): m/z calcd for C13H17O3 [MH+]: 221.1172; found: 221.1173.