Citation: Wen-Jing Liu, De-Sheng Mei, Wen-Hu Duan. Synthesis of 1,7-dimethoxy-2-hydroxyxanthone, a natural product with potential activity on erectile dysfunction[J]. Chinese Chemical Letters, ;2013, 24(6): 515-517. shu

Synthesis of 1,7-dimethoxy-2-hydroxyxanthone, a natural product with potential activity on erectile dysfunction

1.
a School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China;
2.
b Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

Corresponding author: De-Sheng Mei, Wen-Hu Duan,
Received Date: 6 January 2013
Available Online: 7 March 2013

The natural product, 1,7-dimethoxy-2-hydroxyxanthone (1), isolated from Securidaca inappendiculate Hassk, has a potential in the treatment of erectile dysfunction due to its significant relaxation activity on rabbit Corpus cavernosum. However, the isolation of compound 1 is problematic because of its high similarity in structure to its analogs. In this paper, the first synthesis of 1 was reported featuring two key reactions: a copper-catalyzed coupling reaction and an intramolecular cyclization.
- 1,7-Dimethoxy-2-hydroxyxanthone,
- Erectile dysfunction,
- Synthesis,
- Copper-catalyzed coupling reaction
1. [1]
  [1] X.D. Yang, L.Z. Xu, S.L. Yang, Xanthones from the stems of Securidaca inappendiculata, Phytochemistry 127 (2001) 1245-1249.
2. [2]
  [2] T. Bo, X.D. Yang, K.A. Li, Optimized separation of pharmacologically active xanthones from Securidaca inappendiculata by capillary electrophoresis, Chromatographia 55 (2001) 217-223.
3. [3]
  [3] C. Galeffi, E. Federici, J.D. Msonthi, Research on African medicinal plants part XVⅢ new xanthones from Ectiadiopsis oblongifolia and Securidaca longepedunculata, Fitoterapia 61 (1990) 79-81.
4. [4]
  [4] (a) C.N. Lin, M.L. Chung, S.J. Liou, Synthesis and anti-inflammatory effects of xanthone derivatives, J. Pharm. Pharmacol. 48 (1996) 532-538 (for isolated compounds from Securidaca inappendiculata Hassk);
5. [5]
  (b) A. Bashir, M. Hamburger, J.D. Msonthi, et al., Isoflavones and xanthones from Polygala virgata, Phytochemistry 31 (1992) 309-311;
6. [6]
  (c) E.R. Silveira, M.J.C. Falcao, A. Menezes Jr., Pentaoxygenated xanthones from Bredemeyera floribunda, Phytochemistry 39 (1995) 1433-1436.
7. [7]
  [5] N.C. Rakuambo, J.J.M. Meyer, A. Hussein, Xanthone isolated from Securidaca longependunculata with activity against erectile dysfunction, Fitoterapia 75 (2004) 497-499.
8. [8]
  [6] T. Makela, J. Matikainen, K. Wahala, Development of novel hapten for radioimmunoassay of the lignan, enterolactone in plasma (Serum) total synthesis of (±)-trans-5-carboxymethoxyenterolactone and several analogues, Tetrahedron 56 (2000) 1873-1882.
9. [9]
  [7] B. Chen, U. Baumeister, C. Tschierske, Carbohydrate-rod-conjugates-ternary rodcoil molecules forming complex liquid crystal structures, J. Am. Chem. Soc. 127 (2005) 16578-16591.
10. [10]
  [8] (a) S.V. Kessar, Y.P. Gupta, P. Balakrishnan, Benzyne cyclization route to benzo[c]phenanthridine alkaloids. Synthesis of chelerythrine, decarine, and nitidine, J. Org. Chem. 53 (1988) 1708-1713 (for the bromation);
11. [11]
  (b) Y.B. Hu, C.M. Li., J.A. Porco Jr., Exploring chemical diversity of epoxyquinoid natural products: synthesis and biological activity of (-)-jesterone and related molecules, Org. Lett. 3 (2001) 1649-1652;
12. [12]
  (c) T. Nakanishi, M. Suzuki, Revision of the structure of fagaridine based on the comparison of UV and NMR data of synthetic compounds, J. Nat. Prod. 61 (1998) 1263-1267;
13. [13]
  (d) U. Wriede, M. Fernandez, H.W. Moore, Synthesis of halodimethoxy-1,2-benzoquinones, J. Org. Chem. 52 (1987) 4485-4489.
14. [14]
  [9] D.L.J. Clive, M. Sannigrahi, S. Hisaindee, Synthesis of (±)-puraquinonic acid: an inducer of cell differentiation, J. Org. Chem. 66 (2001) 954-961.
15. [15]
  [10] D.L.J. Clive, M.L. Yu, M. Sannigrahi, Synthesis of optically pure (+)-puraquinonic acid and assignment of absolute configuration to natural (±)-puraquinonic acid. Use of radical cyclization for asymmetric generation of a quaternary center, J. Org. Chem. 69 (2004) 4116-4125.
16. [16]
  [11] (a) E. Dalcanale, Selective oxidation of aldehydes to carboxylic acids with sodium chlorite-hydrogen peroxide, J. Org. Chem. 51 (1986) 567-569;
17. [17]
  (b) Spectral data of 9-1: Mp 162-163 ℃. ¹H NMR (400 MHz, CDC_l3): δ 7.46-7.36 (m, 5H), 7.26 (d, 1H, J = 8.8 Hz), 6.92 (d, 1H, J = 8.8 Hz), 5.15 (s, 2H), 3.98 (s, 3H); ¹³C NMR (100 MHz, CDC_l3): δ 167.9, 151.1, 146.6, 136.5, 132.5, 128.3, 127.8, 127.7, 127.3, 115.9, 107.8, 70.6, 60.7; HRMS (EI, m/z): Calcd. for C₁₅H₁₃O₄Br (M⁺): 337.9987, found: 337.9977.
18. [18]
  [12] Spectral data of 7-1: ¹H NMR (400 MHz, CDC_l3): δ 7.47-7.33 (m, 5H), 6.98 (d, 2H, J = 9.2 Hz), 6.93 (d, 1H, J = 8.8 Hz), 6.86 (d, 2H, J = 8.8 Hz), 6.53 (d, 1H, J = 9.2 Hz), 5.10 (s, 2H), 4.01 (s, 3H), 3.80 (s, 3H); ¹³C NMR (100 MHz, CDC_l3): δ 155.9, 150.6, 149.6, 148.0, 147.2, 136.7, 128.6, 128.1, 127.4, 120.5, 117.3, 114.7, 113.2, 71.8, 61.9, 55.6; HRMS (EI, m/z): Calcd. for C22H20O6 (M⁺): 380.1262, found: 380.1260.
19. [19]
  [13] Spectral data of 7-dimethoxy-2-hydroxyxanthone (1): Mp 174-176 8C (lit. [3] mp 174-176 8C); ¹H NMR (400 Hz, CDC_l3): δ 7.70 (d, 1H, J = 3.2 Hz), 7.41 (dd, 2H, J₁ = 9.29.2 Hz, J₂ = 9.23.6 Hz), 7.33 (dd, 1H, J₁ = 9.29.0 Hz, J₂ = 9.23.2 Hz), 7.25 (d, 1H, J = 8.8 Hz), 5.98 (s, 1H), 4.07 (s, 3H), 3.93 (s, 3H); ¹³C NMR (125 MHz, CDC_l3): δ 176.2, 155.9, 151.0, 150.3, 145.1, 144.1, 124.9, 122.3, 122.2, 119.0, 115.5, 114.2, 105.5, 62.6, 55.9; HRMS (EI, m/z): Calcd. for C₁₅H₁₂O₅ (M⁺): 272.0686, found: 272.0685.
20. [20]
  [14] (a) J. Wrobel, J. Millen, J. Sredy, Syntheses of tolrestat analogs containing additional substituents in the ring and their evaluation as aldose reductase inhibitors. Identification of potent, orally active 2-fluoro derivatives, J. Med. Chem. 34 (1991) 2504-2520 (for Ullmann reaction);
21. [21]
  (b) J.R. Goodell, A.A. Madhok, D.M. Ferguson, Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity, Bioorg. Med. Chem. 14 (2006) 5467-5480;
22. [22]
  (c) L. Piazzi, A. Cavali, F. Belluti, Extensive, SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6,7-dimethoxy-2H-2-chromenone(AP2238) derivatives, J. Med. Chem. 50 (2007) 4250-4254.
23. [23]
  [15] (a) N.N. Kulkarni, V.S. Kulkarni, B.D. Hosangadi, Synthetic studies on medium and large ring esters, Tetrahedron 44 (1988) 5145-5149 (for intramolecular cyclization);
24. [24]
  (b) R.H.B. Galt, J. Horury, S. Zbigniew, The xanthene-9-spiro-4'-piperidine nucleus as a probe for opiate activity, J. Med. Chem. 32 (1989) 2357-2362;
25. [25]
  (c) J.S. Sawyer, E.A. Schmittling, J.A. Palkowitz, Synthesis of diaryl ethers, diaryl thioethers, and diarylamines mediated by potassium fluoride-alumina and 18-crown-6: expansion of scope and utility(1), J. Org. Chem. 63 (1998) 6338-6343.
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1.
沈阳化工大学材料科学与工程学院沈阳 110142