注册 English

Synthesis and cytotoxicity evaluation of a novel justicidin G analogue and its phosphate ester

Sheng-Peng Wang ,  Yuan-Feng Tong ,  Dong-Mei Wang ,  Nan Wang ,  Zheng Yan ,  Ping Huang ,  Song Wu

downloadPDF
Citation:  Sheng-Peng Wang, Yuan-Feng Tong, Dong-Mei Wang, Nan Wang, Zheng Yan, Ping Huang, Song Wu. Synthesis and cytotoxicity evaluation of a novel justicidin G analogue and its phosphate ester[J]. Chinese Chemical Letters, 2014, 25(7): 1044-1046. doi: 10.1016/j.cclet.2014.05.042 shu

Synthesis and cytotoxicity evaluation of a novel justicidin G analogue and its phosphate ester

    • 通讯作者: Yuan-Feng Tong,
    Song Wu,
  • 基金项目:

    Technological Special Project for ‘Significant New Drugs Innovation' (No. 2012ZX09301002-001) (No. 2012ZX09301002-001)

    the Union Youth Science & Research Fund (No. 3332013074) for financial support. (No. 3332013074)

摘要: The novel justicidin G analogue 13 and its phosphate ester 15 were synthesized as potential anticancer agents in several steps starting from commercially available methyl gallate and veratraldehyde. The cytotoxicity of the intermediates was tested against HCT-8, BEL-7402, KETR3, HELA, BGC-823, KB and MCF-7 cell lines by the MTT test, and compound 15 exhibited significant cytotoxicity in HELA and KB cell lines.

English

  • 

    1. [1] C.C. Chen, W.C. Hsin, Y.L. Huang, Six new diarylbutane lignans from Justicia procumbens, J. Nat. Prod. 61 (1998) 227-229.[1] C.C. Chen, W.C. Hsin, Y.L. Huang, Six new diarylbutane lignans from Justicia procumbens, J. Nat. Prod. 61 (1998) 227-229.

    2. [2] M.H. Yang, J. Wu, F. Cheng, Y. Zhou, Complete assignments of 1H and 13C NMR data for seven arylnaphthalide lignans from Justicia procumbens, Magn. Reson. Chem. 44 (2006) 727-730.[2] M.H. Yang, J. Wu, F. Cheng, Y. Zhou, Complete assignments of 1H and 13C NMR data for seven arylnaphthalide lignans from Justicia procumbens, Magn. Reson. Chem. 44 (2006) 727-730.

    3. [3] X.L. He, P. Zhang, X.Z. Dong, et al., JR6, a new compound isolated from Justicia procumbens, induces apoptosis in human bladder cancer EJ cells through caspasedependent pathway, J. Ethnopharmacol. 144 (2012) 284-292.[3] X.L. He, P. Zhang, X.Z. Dong, et al., JR6, a new compound isolated from Justicia procumbens, induces apoptosis in human bladder cancer EJ cells through caspasedependent pathway, J. Ethnopharmacol. 144 (2012) 284-292.

    4. [4] F. Qiu, S.J. Zhou, S.J. Fu, et al., LC-ESI-MS/MS analysis and pharmacokinetics of 6'-hydroxy justicidin A, a potential antitumor active component isolated from Justicia procumbens, in rats, J. Pharm. Biomed. 70 (2012) 539-543.[4] F. Qiu, S.J. Zhou, S.J. Fu, et al., LC-ESI-MS/MS analysis and pharmacokinetics of 6'-hydroxy justicidin A, a potential antitumor active component isolated from Justicia procumbens, in rats, J. Pharm. Biomed. 70 (2012) 539-543.

    5. [5] P. Zhang, W.Q. Zhou, X.Z. Dong, M.H. Yang, M.G. Bi, Effect of 6'-hydroxy justicidin A on cell proliferation and redox system in tumor cells, Chin. J. Pharmacol. Toxicol. 24 (2010) 207-213.[5] P. Zhang, W.Q. Zhou, X.Z. Dong, M.H. Yang, M.G. Bi, Effect of 6'-hydroxy justicidin A on cell proliferation and redox system in tumor cells, Chin. J. Pharmacol. Toxicol. 24 (2010) 207-213.

    6. [6] P.Zhang, X.Z.Dong, Y.T.Zhou,M.H.Yang,M.G. Bi,Mechanismof JR6 to inducehuman bladder cancer EJ cells apoptosis, Chin. Pharmacol. Bull. 25 (2009) 173-174.[6] P.Zhang, X.Z.Dong, Y.T.Zhou,M.H.Yang,M.G. Bi,Mechanismof JR6 to inducehuman bladder cancer EJ cells apoptosis, Chin. Pharmacol. Bull. 25 (2009) 173-174.

    7. [7] J.Y. Deng, M.H. Yang, M.G. Bi, In vitro anti-tumor mechanism of JR6 on human colon cancer cell HT-29, Chin. Pharmacol. Bull. 25 (2009) 190-191.[7] J.Y. Deng, M.H. Yang, M.G. Bi, In vitro anti-tumor mechanism of JR6 on human colon cancer cell HT-29, Chin. Pharmacol. Bull. 25 (2009) 190-191.

    8. [8] (a) P. Allevi, M. Anastasia, P. Ciuffreda, E. Bigatti, Stereoselective glucosidation of podophyllum lignans. A new simple synthesis of etoposide, J. Org. Chem. 58 (1993) 4175-4178; (b) M.G. Saulnier, D.R. Langley, J.F. Kadow, Synthesis of etoposide phosphate, BMY-40481: a water-soluble clinically active prodrug of etoposide, Bioorg. Med. Chem. Lett. 4 (1994) 2567-2572.[8] (a) P. Allevi, M. Anastasia, P. Ciuffreda, E. Bigatti, Stereoselective glucosidation of podophyllum lignans. A new simple synthesis of etoposide, J. Org. Chem. 58 (1993) 4175-4178; (b) M.G. Saulnier, D.R. Langley, J.F. Kadow, Synthesis of etoposide phosphate, BMY-40481: a water-soluble clinically active prodrug of etoposide, Bioorg. Med. Chem. Lett. 4 (1994) 2567-2572.

    9. [9] L. Xiong, M.G. Bi, S. Wu, Y.F. Tong, Total synthesis of 6'-hydroxy justicidin A, J. Asian Nat. Prod. Res. 14 (2012) 322-326.[9] L. Xiong, M.G. Bi, S. Wu, Y.F. Tong, Total synthesis of 6'-hydroxy justicidin A, J. Asian Nat. Prod. Res. 14 (2012) 322-326.

    10. [10] (a) S.P. Wang, Y.F. Tong, L. Li, S. Wu, Y. Qi, The synthesis of justicidinoside B and its atropisomer, J. Asian Nat. Prod. Res. 15 (2013) 644-649; (b) J.L. Charlton, C.J. Oleschuk, G.L. Chee, Hindered rotation in arylnaphthalene lignans, J. Org. Chem. 61 (1996) 3452-3457.[10] (a) S.P. Wang, Y.F. Tong, L. Li, S. Wu, Y. Qi, The synthesis of justicidinoside B and its atropisomer, J. Asian Nat. Prod. Res. 15 (2013) 644-649; (b) J.L. Charlton, C.J. Oleschuk, G.L. Chee, Hindered rotation in arylnaphthalene lignans, J. Org. Chem. 61 (1996) 3452-3457.

    11. [11] M.C. Carreno, J.L. Garcia Ruano, G. Sanz, M.A. Toledo, A. Urbano, N-bromosuccinimide in acetonitrile: a mild and regiospecific nuclear brominating reagent for methoxybenzenes and naphthalenes, J. Org. Chem. 60 (1995) 5328-5331.[11] M.C. Carreno, J.L. Garcia Ruano, G. Sanz, M.A. Toledo, A. Urbano, N-bromosuccinimide in acetonitrile: a mild and regiospecific nuclear brominating reagent for methoxybenzenes and naphthalenes, J. Org. Chem. 60 (1995) 5328-5331.

    12. [12] W.G. Zhang, J.G. Lin, X.S. Yao, et al., Total synthesis of two new dihydrostilbenes from Bulbophyllum odoratissimum, J. Asian Nat. Prod. Res. 9 (2007) 23-28.[12] W.G. Zhang, J.G. Lin, X.S. Yao, et al., Total synthesis of two new dihydrostilbenes from Bulbophyllum odoratissimum, J. Asian Nat. Prod. Res. 9 (2007) 23-28.

    13. [13] Data of compounds 3 and 8. Compound 3: White solid, mp 95-96℃. 1H NMR (300 MHz, DMSO-d6): δ 3.74 (s, 3H, -OCH3), 3.77 (s, 3H, -OCH3), 3.98-3.89 (m, 2H, C-CH2-C), 4.14-4.03 (m, 2H, C-CH2-C), 5.82 (s, 1H, Ar-CH-O), 7.03 (s, 1H, Ar-H), 7.12 (s, 1H, Ar-H). 13C NMR (100 MHz, DMSO-d6):δ190.8, 155.2, 149.3, 126.4, 120.0, 116.6, 111.1, 65.5, 63.5, 57.1, 56.3. HRESIMS Calcd. for C11H14BrO4 [M+H]+: 289.0070, found: 289.0064. Compound 8: White solid, mp 66-68℃. 1H NMR (400 MHz, DMSO-d6):δ5.23 (s, 2H, Ar-CH2-O), 6.14 (s, 2H, O-CH2-O), 7.09 (s, 1H, Ar-H), 7.61-7.19 (m, 6H, Ar-H×6), 9.75 (s, 1H, -CHO). 13CNMR(100 MHz, DMSOd6):δ191.5, 149.9, 143.2, 141.6, 137.0, 132.1, 129.2, 128.8, 128.6, 113.6, 103.4, 103.1, 71.3. HRESIMS Calcd. for C15H13O4 [M+H]+: 257.0808, found: 257.0799.[13] Data of compounds 3 and 8. Compound 3: White solid, mp 95-96℃. 1H NMR (300 MHz, DMSO-d6): δ 3.74 (s, 3H, -OCH3), 3.77 (s, 3H, -OCH3), 3.98-3.89 (m, 2H, C-CH2-C), 4.14-4.03 (m, 2H, C-CH2-C), 5.82 (s, 1H, Ar-CH-O), 7.03 (s, 1H, Ar-H), 7.12 (s, 1H, Ar-H). 13C NMR (100 MHz, DMSO-d6):δ190.8, 155.2, 149.3, 126.4, 120.0, 116.6, 111.1, 65.5, 63.5, 57.1, 56.3. HRESIMS Calcd. for C11H14BrO4 [M+H]+: 289.0070, found: 289.0064. Compound 8: White solid, mp 66-68℃. 1H NMR (400 MHz, DMSO-d6):δ5.23 (s, 2H, Ar-CH2-O), 6.14 (s, 2H, O-CH2-O), 7.09 (s, 1H, Ar-H), 7.61-7.19 (m, 6H, Ar-H×6), 9.75 (s, 1H, -CHO). 13CNMR(100 MHz, DMSOd6):δ191.5, 149.9, 143.2, 141.6, 137.0, 132.1, 129.2, 128.8, 128.6, 113.6, 103.4, 103.1, 71.3. HRESIMS Calcd. for C15H13O4 [M+H]+: 257.0808, found: 257.0799.

    14. [14] Data of compounds 9-14. Compound 9: White solid, mp 115-116℃. 1H NMR (400 MHz, DMSO-d6):δ3.66 (s, 3H, -OCH3), 3.72 (s, 3H, -OCH3), 3.97-3.84 (m, 2H, C-CH2-C), 4.11-3.98 (m, 2H, C-CH2-C), 5.10 (s, 2H, Ar-CH2-O), 5.75 (s, 1H, Ar-CH-O), 5.90 (s, 1H, Ar-CH-Ar), 5.92 (s, 2H, O-CH2-O), 6.47 (s, 1H, Ar-H), 6.70 (s, 1H, Ar-H), 6.92 (s, 1H, Ar-H), 6.97 (s, 1H, Ar-H), 7.48-7.21 (m, 5H, Ar-H×5). 13C NMR (125 MHz, DMSO-d6):δ149.7, 148.8, 147.9, 142.1, 140.5, 137.4, 137.1, 134.2, 128.8, 128.4, 128.2, 126.7, 111.0, 109.9, 108.3, 101.5, 101.2, 100.5, 71.0, 69.3, 65.1, 56.1, 56.0. HRESIMS Calcd. for C26H26NaO8 [M+Na]+: 489.1520, found: 489.1512. Compound 10: White solid,mp 162-164℃. 1H NMR (400 MHz, DMSOd6):δ0.94 (t, 3H, J=7.1 Hz, -CH3), 1.25 (t, 3H, J=7.1 Hz, -CH3), 3.60 (s, 3H-OCH3), 3.93 (s, 3H, -OCH3), 3.95 (q, 2H, J=7.1 Hz, C-CH2-C), 4.33 (q, 3H, J=7.1 Hz, C-CH2-C), 5.14 (s, 2H, Ar-CH2-O), 6.06 (s, 1H, O-CH-O), 6.09 (s, 1H, O-CH-O), 6.45 (s, 1H, Ar-H), 6.56 (s, 1H, Ar-H), 6.71 (s, 1H, Ar-H), 7.48-7.27 (m, 5H, Ar-H×5), 7.63 (s, 1H, Ar-H), 11.92 (s, 1H, Ar-OH). 13C NMR (125 MHz, DMSO-d6):δ169.0, 168.6, 157.3, 152.2, 151.5, 149.1, 148.1, 141.6, 136.7, 134.5, 131.4, 130.7, 129.4, 128.4, 127.9, 127.6, 111.7, 105.6, 104.7, 103.2, 102.6, 101.4, 76.9, 70.4, 55.5, 55.2, 52.3, 51.6, 13.6, 13.5. HRESIMS Calcd. for C32H31O10 [M+H]+: 575.1912, found: 575.1902. Compound 11: White solid, mp 206-207℃. 1H NMR (300 MHz, DMSO-d6):δ3.58 (s, 3H, -OCH3), 3.92 (s, 3H, -OCH3), 5.13 (s, 2H, Ar-CH2-O), 5.36 (s, 2H, Ar-CH2-O), 6.09 (s, 2H, O-CH2-O), 6.53 (s, 1H, Ar-H), 6.62 (s, 1H, Ar-H), 6.90 (s, 1H, Ar-H), 7.46-7.24 (m, 5H, Ar-H×5), 7.62 (s, 1H, Ar-H), 10.50 (s, 1H, Ar-OH). 13C NMR (150 MHz, DMSO-d6):δ169.5, 150.5, 149.7, 148.1, 144.9, 141.7, 136.8, 134.7, 129.4, 129.4, 129.3, 128.4, 127.9, 127.7, 123.2, 121.7, 118.7, 111.4, 105.5, 105.0, 101.3, 100.7, 70.4, 66.6, 55.5, 55.1. HRESIMS Calcd. for C28H23O8[14] Data of compounds 9-14. Compound 9: White solid, mp 115-116℃. 1H NMR (400 MHz, DMSO-d6):δ3.66 (s, 3H, -OCH3), 3.72 (s, 3H, -OCH3), 3.97-3.84 (m, 2H, C-CH2-C), 4.11-3.98 (m, 2H, C-CH2-C), 5.10 (s, 2H, Ar-CH2-O), 5.75 (s, 1H, Ar-CH-O), 5.90 (s, 1H, Ar-CH-Ar), 5.92 (s, 2H, O-CH2-O), 6.47 (s, 1H, Ar-H), 6.70 (s, 1H, Ar-H), 6.92 (s, 1H, Ar-H), 6.97 (s, 1H, Ar-H), 7.48-7.21 (m, 5H, Ar-H×5). 13C NMR (125 MHz, DMSO-d6):δ149.7, 148.8, 147.9, 142.1, 140.5, 137.4, 137.1, 134.2, 128.8, 128.4, 128.2, 126.7, 111.0, 109.9, 108.3, 101.5, 101.2, 100.5, 71.0, 69.3, 65.1, 56.1, 56.0. HRESIMS Calcd. for C26H26NaO8 [M+Na]+: 489.1520, found: 489.1512. Compound 10: White solid,mp 162-164℃. 1H NMR (400 MHz, DMSOd6):δ0.94 (t, 3H, J=7.1 Hz, -CH3), 1.25 (t, 3H, J=7.1 Hz, -CH3), 3.60 (s, 3H-OCH3), 3.93 (s, 3H, -OCH3), 3.95 (q, 2H, J=7.1 Hz, C-CH2-C), 4.33 (q, 3H, J=7.1 Hz, C-CH2-C), 5.14 (s, 2H, Ar-CH2-O), 6.06 (s, 1H, O-CH-O), 6.09 (s, 1H, O-CH-O), 6.45 (s, 1H, Ar-H), 6.56 (s, 1H, Ar-H), 6.71 (s, 1H, Ar-H), 7.48-7.27 (m, 5H, Ar-H×5), 7.63 (s, 1H, Ar-H), 11.92 (s, 1H, Ar-OH). 13C NMR (125 MHz, DMSO-d6):δ169.0, 168.6, 157.3, 152.2, 151.5, 149.1, 148.1, 141.6, 136.7, 134.5, 131.4, 130.7, 129.4, 128.4, 127.9, 127.6, 111.7, 105.6, 104.7, 103.2, 102.6, 101.4, 76.9, 70.4, 55.5, 55.2, 52.3, 51.6, 13.6, 13.5. HRESIMS Calcd. for C32H31O10 [M+H]+: 575.1912, found: 575.1902. Compound 11: White solid, mp 206-207℃. 1H NMR (300 MHz, DMSO-d6):δ3.58 (s, 3H, -OCH3), 3.92 (s, 3H, -OCH3), 5.13 (s, 2H, Ar-CH2-O), 5.36 (s, 2H, Ar-CH2-O), 6.09 (s, 2H, O-CH2-O), 6.53 (s, 1H, Ar-H), 6.62 (s, 1H, Ar-H), 6.90 (s, 1H, Ar-H), 7.46-7.24 (m, 5H, Ar-H×5), 7.62 (s, 1H, Ar-H), 10.50 (s, 1H, Ar-OH). 13C NMR (150 MHz, DMSO-d6):δ169.5, 150.5, 149.7, 148.1, 144.9, 141.7, 136.8, 134.7, 129.4, 129.4, 129.3, 128.4, 127.9, 127.7, 123.2, 121.7, 118.7, 111.4, 105.5, 105.0, 101.3, 100.7, 70.4, 66.6, 55.5, 55.1. HRESIMS Calcd. for C28H23O8

    15. [M+H]+: 487.1387, found: 487.1391. Compound 12: White solid, mp 223-224℃. 1H NMR (300 MHz, DMSO-d6):δ3.58 (s, 3H, -OCH3), 3.93 (s, 3H, -OCH3), 4.12 (s, 3H, -OCH3), 5.13 (s, 2H, Ar-CH2-O), 5.70 (s, 2H, Ar-CH2-O), 6.10 (s, 2H, O-CH2-O), 6.54 (s, 1H, Ar-H), 6.62 (s, 1H, Ar-H), 6.89 (s, 1H, Ar-H), 7.45-7.25 (m, 5H, Ar-H×5), 7.50 (s, 1H, Ar-H). 13C NMR (125 MHz, acetone-d6):δ168.9, 151.3, 150.1, 148.3, 147.3, 141.8, 136.9, 134.9, 132.6, 129.5, 129.1, 128.4, 128.0, 127.7, 124.9, 123.9, 119.1, 111.4, 105.7, 104.8, 101.4, 100.6, 70.6, 66.8, 59.2, 55.8, 55.3. HRESIMS Calcd. for C29H25O8 [M+H]+: 501.1544, found: 501.1535. Compound 13: White solid, mp 142-143℃. 1H NMR (300 MHz, DMSO-d6):δ3.66 (s, 3H, -OCH3), 3.93 (s, 3H, -OCH3), 4.12 (s, 3H, -OCH3), 5.69 (s, 2H, Ar-CH2-O), 6.03 (s, 2H, O-CH2-O), 6.32 (s, 1H, Ar-H), 6.35 (s, 1H, Ar-H), 6.97 (s, 1H, Ar-H), 7.50 (s, 1H, Ar-H), 9.73 (s, 1H, Ar-OH). 13C NMR (100 MHz, DMSO-d6):δ169.6, 151.9, 150.6, 148.9, 147.8, 141.2, 134.2, 133.5, 130.1, 129.4, 125.5, 124.4, 119.6, 113.9, 106.3, 103.2, 101.5, 101.2, 67.4, 59.7, 56.3, 55.9. HRESIMS Calcd. for C22H19O8 [M+H]+: 411.1074, found: 411.1072. Compound 14: Yellowish solid, mp 157-158℃. 1H NMR (400 MHz, DMSO-d6):δ3.60 (s, 3H-OCH3), 3.95 (s, 3H-OCH3), 4.14 (s, 3H-OCH3), 5.14-5.16 (m, 4H, Ar-CH2-O×2), 5.73 (s, 2H, Ar-CH2-O), 6.12 (s, 1H, O-CH-O), 6.13 (s, 1H, O-CH-O), 6.68 (s, 1H, Ar-H), 6.81 (s, 1H, Ar-H), 6.92 (s, 1H, Ar-H), 7.39-7.10 (m, 10H, Ar-H 1'), 7.52 (s, 1H, Ar-H). 13C NMR (125 MHz, DMSO-d6)δ169.4, 151.8, 150.3, 150.2, 148.1, 140.1, 139.5, 139.5, 133.3, 133.3, 130.4, 129.7, 129.7, 126.8, 126.8, 119.9, 119.9, 113.2, 110.9, 106.3, 101.7, 101.4, 98.2, 67.0, 60.2, 56.1, 55.8. 31P NMR (200 MHz, DMSO-d6):δ6.28. HRESIMS Calcd. for C36H31NaO11P [M+Na]+: 693.1496, found: 693.1492.[M+H]+: 487.1387, found: 487.1391. Compound 12: White solid, mp 223-224℃. 1H NMR (300 MHz, DMSO-d6):δ3.58 (s, 3H, -OCH3), 3.93 (s, 3H, -OCH3), 4.12 (s, 3H, -OCH3), 5.13 (s, 2H, Ar-CH2-O), 5.70 (s, 2H, Ar-CH2-O), 6.10 (s, 2H, O-CH2-O), 6.54 (s, 1H, Ar-H), 6.62 (s, 1H, Ar-H), 6.89 (s, 1H, Ar-H), 7.45-7.25 (m, 5H, Ar-H×5), 7.50 (s, 1H, Ar-H). 13C NMR (125 MHz, acetone-d6):δ168.9, 151.3, 150.1, 148.3, 147.3, 141.8, 136.9, 134.9, 132.6, 129.5, 129.1, 128.4, 128.0, 127.7, 124.9, 123.9, 119.1, 111.4, 105.7, 104.8, 101.4, 100.6, 70.6, 66.8, 59.2, 55.8, 55.3. HRESIMS Calcd. for C29H25O8 [M+H]+: 501.1544, found: 501.1535. Compound 13: White solid, mp 142-143℃. 1H NMR (300 MHz, DMSO-d6):δ3.66 (s, 3H, -OCH3), 3.93 (s, 3H, -OCH3), 4.12 (s, 3H, -OCH3), 5.69 (s, 2H, Ar-CH2-O), 6.03 (s, 2H, O-CH2-O), 6.32 (s, 1H, Ar-H), 6.35 (s, 1H, Ar-H), 6.97 (s, 1H, Ar-H), 7.50 (s, 1H, Ar-H), 9.73 (s, 1H, Ar-OH). 13C NMR (100 MHz, DMSO-d6):δ169.6, 151.9, 150.6, 148.9, 147.8, 141.2, 134.2, 133.5, 130.1, 129.4, 125.5, 124.4, 119.6, 113.9, 106.3, 103.2, 101.5, 101.2, 67.4, 59.7, 56.3, 55.9. HRESIMS Calcd. for C22H19O8 [M+H]+: 411.1074, found: 411.1072. Compound 14: Yellowish solid, mp 157-158℃. 1H NMR (400 MHz, DMSO-d6):δ3.60 (s, 3H-OCH3), 3.95 (s, 3H-OCH3), 4.14 (s, 3H-OCH3), 5.14-5.16 (m, 4H, Ar-CH2-O×2), 5.73 (s, 2H, Ar-CH2-O), 6.12 (s, 1H, O-CH-O), 6.13 (s, 1H, O-CH-O), 6.68 (s, 1H, Ar-H), 6.81 (s, 1H, Ar-H), 6.92 (s, 1H, Ar-H), 7.39-7.10 (m, 10H, Ar-H 1'), 7.52 (s, 1H, Ar-H). 13C NMR (125 MHz, DMSO-d6)δ169.4, 151.8, 150.3, 150.2, 148.1, 140.1, 139.5, 139.5, 133.3, 133.3, 130.4, 129.7, 129.7, 126.8, 126.8, 119.9, 119.9, 113.2, 110.9, 106.3, 101.7, 101.4, 98.2, 67.0, 60.2, 56.1, 55.8. 31P NMR (200 MHz, DMSO-d6):δ6.28. HRESIMS Calcd. for C36H31NaO11P [M+Na]+: 693.1496, found: 693.1492.

    16. [15] Compound 15: White solid, mp 212-213℃. The HRESIMS of 15 established a molecular formula of C22H19O11P [m/z 513.0642 (M+Na)+, Calcd. for C22H19NaO11P: 513.0640], indicating 14 degrees of unsaturation. 1H NMR spectrum showed three methoxy groups [δH 3.70 (s, 3H, H-13), 3.94 (s, 3H, H-14), 4.13 (s, 3H, H-15)] and four aromatic protons [δH 7.51 (s, 1H, H-5), 7.05 (s, 1H, H-8), 6.70 (s, 1H, H-20), 6.83 (s, 1H, H-60)]. 13C NMR and DEPT spectra exhibited 22 carbons, including three methyls, two methylenes, sixteen quaternary carbons and one carbonyl. 31P NMR spectrum revealed the existence of one phosphate ester. The HMBC correlations of H-5/C-4, C-7, C-9 and H-8/C-1, C-6, C-10 revealed the present of naphthyl (ring A and ring B). The correlations from H-12 to C-2, C-3, C-4 and C-11 suggested the present of ring C. The correlations of H-13/C-7, H-14/ C-6 and H-15/C-4 gave the substituted positions of three methoxy groups. The linkage of ring B and D was elucidated by the HMBC correlations from H-20 and H-60 to C-1 and C-10. The correlations from H-70 to C-40 and C-50 revealed the presence of ring E. The planar structure of 15 was thus established. 1H NMR (400 MHz, DMSO-d6):δ7.51 (s, 1H, H-5), 7.05 (s, 1H, H-8), 5.71 (s, 2H, H-12), 3.70 (s, 3H, H-13), 3.94 (s, 3H, H-14), 4.13 (s, 3H, H-15), 6.70 (s, 1H, H-20), 6.83 (s, 1H, H-60), 6.13 (d, 2H, J=4.1 Hz, H-70). 13C NMR (125 MHz, DMSO-d6):δ132.3 (C-1), 116.9 (C-2), 119.4 (C-3), 147.8 (C-4), 101.3 (C-5), 151.7 (C-6), 150.5 (C-7), 106.0 (C-8), 128.6 (C-9), 129.7 (C-1'), 169.4 (C-11), 67.3 (C-12), 55.7 (C-13), 56.1 (C-14), 59.6 (C-15), 125.3 (C-1'), 107.6 (C-2'), 148.9 (C-3'), 137.2 (C-4'), 148.9 (C-5'), 116.9 (C-6'), 102.1 (C-7'). 31P NMR (200 MHz, DMSO-d6):δ5.83.[15] Compound 15: White solid, mp 212-213℃. The HRESIMS of 15 established a molecular formula of C22H19O11P [m/z 513.0642 (M+Na)+, Calcd. for C22H19NaO11P: 513.0640], indicating 14 degrees of unsaturation. 1H NMR spectrum showed three methoxy groups [δH 3.70 (s, 3H, H-13), 3.94 (s, 3H, H-14), 4.13 (s, 3H, H-15)] and four aromatic protons [δH 7.51 (s, 1H, H-5), 7.05 (s, 1H, H-8), 6.70 (s, 1H, H-20), 6.83 (s, 1H, H-60)]. 13C NMR and DEPT spectra exhibited 22 carbons, including three methyls, two methylenes, sixteen quaternary carbons and one carbonyl. 31P NMR spectrum revealed the existence of one phosphate ester. The HMBC correlations of H-5/C-4, C-7, C-9 and H-8/C-1, C-6, C-10 revealed the present of naphthyl (ring A and ring B). The correlations from H-12 to C-2, C-3, C-4 and C-11 suggested the present of ring C. The correlations of H-13/C-7, H-14/ C-6 and H-15/C-4 gave the substituted positions of three methoxy groups. The linkage of ring B and D was elucidated by the HMBC correlations from H-20 and H-60 to C-1 and C-10. The correlations from H-70 to C-40 and C-50 revealed the presence of ring E. The planar structure of 15 was thus established. 1H NMR (400 MHz, DMSO-d6):δ7.51 (s, 1H, H-5), 7.05 (s, 1H, H-8), 5.71 (s, 2H, H-12), 3.70 (s, 3H, H-13), 3.94 (s, 3H, H-14), 4.13 (s, 3H, H-15), 6.70 (s, 1H, H-20), 6.83 (s, 1H, H-60), 6.13 (d, 2H, J=4.1 Hz, H-70). 13C NMR (125 MHz, DMSO-d6):δ132.3 (C-1), 116.9 (C-2), 119.4 (C-3), 147.8 (C-4), 101.3 (C-5), 151.7 (C-6), 150.5 (C-7), 106.0 (C-8), 128.6 (C-9), 129.7 (C-1'), 169.4 (C-11), 67.3 (C-12), 55.7 (C-13), 56.1 (C-14), 59.6 (C-15), 125.3 (C-1'), 107.6 (C-2'), 148.9 (C-3'), 137.2 (C-4'), 148.9 (C-5'), 116.9 (C-6'), 102.1 (C-7'). 31P NMR (200 MHz, DMSO-d6):δ5.83.

    17. [16] National Pharmacopoeia Committee, Pharmacopoeia of People’s Republic of China. Part 2, vol. XIV, Chemical Industry Press, Beijing, 2010.[16] National Pharmacopoeia Committee, Pharmacopoeia of People’s Republic of China. Part 2, vol. XIV, Chemical Industry Press, Beijing, 2010.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  1427
  • HTML全文浏览量:  41
文章相关
  • 收稿日期:  2014-03-31
  • 网络出版日期:  2014-05-21
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net