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Synlett 2009(9): 1501-1505  
DOI: 10.1055/s-0029-1217174
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a New Class of Spirophenanthrones

Xue-song Wu, Shuang-zheng Lin, Ming-zong Li, Tian-pa You*
Department of Chemistry, University of Science and Technology of China, Hefei 230026, P. R. of China
e-Mail: ytp@ustc.edu.cn;
Further Information

Publication History

Received 2 January 2009
Publication Date:
13 May 2009 (online)

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Abstract

Using 5 mol% of proline as a recoverable catalyst, 9-phenanthrols react with formaldehyde at room temperature, through Mannich bases and 10-methylene-9-phenanthrone intermediates, to form a new class of spirophenanthrones.

Key words

polymethoxyaromatics - Mannich bases - hetero Diels-Alder reaction - 10-methylene-9-phenanthrone - dimerization

    References and Notes

  • 1a Choi Y.-W. Takamatsu S. Khan SI. Srinivas PV. Ferreira D. Zhao J. J. Nat. Prod.  2006,  69:  356 
    Google Scholar
  • 1b Chen M. Kilgore N. Lee K.-H. Chen D.-F. J. Nat. Prod.  2006,  69:  1697 
    Google Scholar
  • 2a Xia Y. Yang Z.-Y. Xia P. Bastow KF. Kuo S.-C. Li K.-H. J. Med. Chem.  1998,  41:  1155 
    Google Scholar
  • 2b Freyer AJ. Abu Zarga MH. Firdous S. Shamma M. J. Nat. Prod.  1987,  50:  684 
    Google Scholar
  • 3a Gupta S. Das L. Datta AB. Poddar A. Janik ME. Bhattacharrya B. Biochemistry  2006,  45:  6467 
    Google Scholar
  • 3b Charlton JL. J. Nat. Prod.  1998,  61:  1447 
    Google Scholar
  • 4a Damu AG. Kuo P.-C. Shi L.-S. Li C.-Y. Kuoh C.-S. Wu P.-L. Wu T.-S. J. Nat. Prod.  2005,  68:  1071 
    Google Scholar
  • 4b Wei L. Shi Q. Bastow KF. Brossi A. Morris-Natschke SL. Nakagawa-Goto K. Wu T.-S. Pan S.-L. Teng C.-M. Lee K.-H. J. Med. Chem.  2007,  50:  3674 
    Google Scholar
  • 4c Stark D. Lykkeberg AK. Christensen J. Budnik BA. Abe F. Jaroszewski JW. J. Nat. Prod.  2002,  65:  1299 
    Google Scholar
  • 5 Bilgic S. Bilgic O. Bueyuekkidan B. Guenduez M. J. Chem. Res.  2007,  2:  76 
    Google Scholar
  • 6 Chauhan MS. Mckinon DM. Can. J. Chem.  1981,  59:  2223 
    CrossrefGoogle Scholar
  • 7a Weinert E. Dondi R. Colloredo-Melz S. Frankenfield KN. Mitchell CH. Freccero M. Rokita SE. J. Am. Chem. Soc.  2006,  128:  11940 
    Google Scholar
  • 7b Gardner PD. Sarrafizadeh HR. Brandon RL. J. Am. Chem. Soc.  1959,  81:  5515 
    Google Scholar
  • 8a Lin S.-Z. Chen Q.-A. You T.-P. Synlett  2007,  2101 
    Google Scholar
  • 8b Lin S.-Z. You T.-P. Tetrahedron  2008,  64:  9906 
    Google Scholar
9

Synthesis of the Dimer of 10-Methylene-9-phenanthrones 1a-g - General Procedure To a stirred suspension of the 9-phenanthrol (1 mmol) in MeOH (10mL, 9d was in THF-MeOH = 4:1), l-proline (6 mg, 0.05 mmol) and 36% aq formaldehyde (0.1 mL, 1.2 mmol) were added. The mixture was stirred at r.t. for 2-4 h. The reaction product was evaporated under vacuum. The residue was purified by flash column chromatography on SiO2, eluting with PE-EtOAc, to produce the dimer of 10-methylene-9-phenanthrones.

10

Selective Spectroscopic Data of the Dimer of 10-Methylene-9-phenanthrones Compound 1a: ¹H NMR (300 MHz, CDCl3): δ = 2.29 (m, 1 H), 2.54-2.60 (m, 2 H), 2.92 (m, 1 H), 3.72 (s, 3 H), 3.74 (s, 3 H), 3.77 (s, 3 H), 3.87 (s, 3 H), 3.89 (s, 3 H), 3.91 (s, 3 H), 3.96 (s, 6 H), 4.00 (s, 3 H), 4.02 (s, 3 H), 4.03 (s, 3 H), 4.06 (s, 3 H), 6.83 (s, 1 H), 7.11 (s, 1 H), 7.26 (s, 1 H), 7.68 (s, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 20.6, 32.8, 55.9, 55.9, 56.1, 56.3, 61.0, 61.1, 61.1, 61.2, 61.2, 61.3, 61.4, 61.5, 83.1, 97.4, 98.0, 103.6, 105.2, 107.7, 113.1, 116.3, 117.7, 121.5, 123.1, 124.9, 132.4, 140.3, 142.3, 142.5, 146.7, 151.7, 151.8, 152.0, 152.2, 152.3, 152.4, 153.2, 153.6, 197.6. HRMS-FAB: m/z [M + H]+ calcd for C42H44O14: 773.2809; found: 773.2810. Anal. Calcd for C42H44O14: C, 65.28; H, 5.74; O, 28.98. Found: C, 65.41; H, 5.72; O, 28.92.
Compound 1b: ¹H NMR (300 MHz, CDCl3): δ = 2.27 (m, 1 H), 2.51 (m, 1 H), 2.82 (m, 1 H), 3.04 (m, 1 H), 3.83 (s, 3 H), 3.93 (s, 3 H), 3.96 (s, 3 H), 3.99 (s, 3 H), 4.00 (s, 3 H), 4.04 (s, 3 H), 4.10 (s, 3 H), 4.11 (s, 3 H), 4.14 (s, 3 H), 7.14 (s, 1 H), 7.24 (s, 1 H), 7.29 (s, 1 H), 7.36 (s, 1 H), 7.42 (s, 1 H), 7.52 (s, 1 H), 7.83 (m, 3 H). ¹³C NMR (75 MHz, CDCl3):
δ = 19.6, 34.1, 55.8, 55.8, 56.0, 56.1, 56.2, 56.2, 56.3, 56.5, 82.3, 102.5, 103.1, 103.3, 103.9, 104.7, 106.9, 107.4, 108.7, 109.2, 119.7, 119.9, 121.5, 122.5, 124.6, 126.1, 131.6, 133.8, 146.6, 147.1, 148.7, 148.9, 149.0, 149.1, 149.2, 149.9, 154.5, 198.1. HRMS-FAB: m/z [M + H]+ calcd for C38H36O10: 653.2387; found: 653.2389. Anal. Calcd for C38H36O10: C, 69.93; H, 5.56; O, 24.51. Found: C, 69.77; H, 5.50; O, 24.60.
Compound 1c: ¹H NMR (300 MHz, CDCl3): δ = 2.27 (m, 1 H), 2.54 (m, 1 H), 2.60 (m, 1 H), 2.91 (m, 1 H), 3.89 (s, 3 H), 3.94 (s, 3 H), 3.99 (s, 3 H), 4.02 (s, 3 H), 6.03 (d, 2 H), 6.14 (d, 2 H), 6.17 (d, 2 H), 6.21 (d, 2 H), 6.80 (s, 1 H), 7.12 (s, 1 H), 7.17 (s, 1 H), 7.70 (s, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 20.9, 33.9, 56.2, 56.3, 56.6, 56.7, 83.3, 97.4, 98.0, 101.2, 101.3, 101.8, 102.4, 102.8, 103.8, 106.1, 108.1, 115.1, 116.2, 117.9, 122.1, 123.4, 125.2, 132.6, 141.3, 142.3, 142.6, 145.0, 151.6, 151.8, 152.0, 152.2, 152.4, 152.5, 153.6, 154.2, 197.0. HRMS-FAB: m/z [M + H]+ calcd for C38H28O14: 709.1557; found: 709.1554. Anal. Calcd for C38H28O14: C, 64.41; H, 3.98; O, 31.61. Found: C, 64.19; H, 3.41; O, 31.55.
Compound 1d: ¹H NMR (300 MHz, DMSO-d 6): δ = 2.24 (m, 1 H), 2.33 (m, 1 H), 2.68 (m, 1 H), 3.42 (m, 1 H), 5.92 (s, 1 H), 6.06 (s, 2 H), 6.08 (s, 1 H), 6.09 (s, 1 H), 6.10 (s, 1 H), 6.19 (s, 1 H), 6.24 (s, 1 H), 7.02 (d, 1 H), 7.12 (d, 1 H), 7.26 (d, 1 H), 7.28 (d, 1 H), 7.55 (d, 1 H), 7.58 (d, 1 H), 8.16 (s, 1 H), 8.19 (s, 1 H). ¹³C NMR (75 MHz, DMSO-d 6): δ = 20.0, 28.9, 80.2, 100.6, 101.1, 101.6, 108.8, 109.4, 111.8, 113.8, 116.4, 117.1, 117.4, 118.1, 120.0, 122.1, 124.1, 126.2, 129.7, 141.9, 144.9, 145.3, 145.7, 146.6, 147.9, 148.2, 193.7. HRMS-FAB: m/z [M + H]+ calcd for C34H20O10: 589.1135; found: 589.1136. Anal. Calcd for C34H20O10: C, 69.39; H, 3.43; O, 27.19. Found: C, 69.54; H, 3.52; O, 27.05.
Compound 1e: ¹H NMR (300 MHz, CDCl3): δ = 2.22 (m, 1 H), 2.46 (s, 3 H), 2.49 (m, 1 H), 2.52 (s, 3 H), 2.58 (s, 3 H), 2.63 (s, 3 H), 2.76 (m, 1 H), 3.01 (m, 1 H), 7.22 (m, 2 H), 7.38 (d, 1 H), 7.45 (d, 1 H), 7.65-7.83 (m, 5 H), 8.38 (m, 3 H). ¹³C NMR (75 MHz, CDCl3): δ = 19.3, 21.4, 22.1, 22.2, 22.3, 34.0, 83.2, 108.5, 122.2, 122.4, 122.8, 123.6, 124.0, 125.0, 126.0, 126.3, 126.8, 127.9, 128.1, 128.3, 129.4, 129.9, 130.1, 133.0, 136.0, 136.8, 137.2, 137.7, 138.2, 145.3, 198.1. HRMS-FAB: m/z [M + H]+ calcd for C34H28O2: 469.2168; found: 469.2165. Anal. Calcd for C34H28O2: C, 87.15; H, 6.02; O, 6.83. Found: C, 87.06; H, 5.98; O, 6.79.
Compound 1f: ¹H NMR (300 MHz, CDCl3): δ = 2.28 (td, 1 H), 2.55 (d, 1 H), 2.80 (td, 1 H), 3.09 (d, 1 H), 7.25-7.89 (m, 13 H), 8.52 (d, 1 H), 8.68 (t, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 19.5, 33.8, 83.2, 108.5, 122.4, 122.5, 123.0, 123.3, 124.0, 124.6, 126.0, 126.7, 128.8, 129.6, 130.1, 130.7, 132.0, 134.8, 136.9, 140.1, 148.0, 198.6. HRMS-FAB: m/z [M + H]+ calcd for C30H20O2: 413.1542; found: 413.1544. Anal. Calcd for C30H20O2: C, 87.36; H, 4.89; O, 7.76. Found: C, 86.92; H, 4.88; O, 7.73.
Compound 1g: ¹H NMR (300 MHz, CDCl3): δ = 2.26 (m, 1 H), 2.50 (m, 1 H), 2.76 (m, 1 H), 3.01 (m, 1 H), 7.17 (m, 2 H), 7.37 (m, 2 H), 7.55 (m, 2 H), 7.74-7.85 (m, 2 H), 7.97 (m, 1 H), 8.15 (m, 2 H), 8.44 (m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 19.4, 33.9, 82.6, 102.2, 107.4, 107.9, 108.3, 108.6, 110.3, 110.6, 110.7, 111.5, 111.8, 115.8, 116.0, 116.2, 116.4, 116.7, 117.1, 117.4, 124.5, 124.6, 125.0, 125.1, 128.2, 128.3, 131.0, 131.1, 196.3. HRMS-FAB: m/z [M + H]+ calcd for C30H16F4O2: 485.1165; found: 485.1169. Anal. Calcd for C30H16F4O2: C, 74.38; H, 3.33; F, 15.69; O, 6.61. Found: C, 74.55; H, 3.39; F, 15.58; O, 6.66.