注册 English

Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine

Jian Yang ,  Ju-Rong Li ,  Jing-Xiang Yang ,  Long-Long Li ,  Wen-Jie Ouyang ,  Shu-Wen Wu ,  Fang Zhang

downloadPDF
Citation:  Jian Yang, Ju-Rong Li, Jing-Xiang Yang, Long-Long Li, Wen-Jie Ouyang, Shu-Wen Wu, Fang Zhang. Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine[J]. Chinese Chemical Letters, 2014, 25(7): 1052-1056. doi: 10.1016/j.cclet.2014.05.030 shu

Synthesis and anti-HIV-1 activity of the conjugates of gossypol with oligopeptides and D-glucosamine

    • 通讯作者: Jian Yang,
  • 基金项目:

    We gratefully acknowledge the National Natural Science Foundation of China (No. 30770228) for financial support. (No. 30770228)

摘要: A series of novel gossypol derivatives were synthesized and screened for their in vitro anti-HIV-1 activity. The results showed that replacing the aldehyde groups of gossypol with certain oligopeptides and Dglucosamine not only reduced the cytotoxicity of gossypol derivatives but also enhanced their antiviral activity against HIV-1. Interestingly, D-glucosamine derivative of gossypol that lacked the COONa group also exhibited the same potent anti-HIV-1 activity as oligopeptide derivatives with the COONa group. These compounds blocked the entry of HIV-1IIIB into target cell, which was similar to T20. Furthermore, the molecular docking analysis rationalized their anti-HIV-1 activity. The results also implied that certain oligopeptides and D-glucosaminewere important moities to prepare gossypol derivatives as HIV-1 entry inhibitors besides certain amino acids.

English

  • 

    1. [1] R. Adams, T.A. Geissman, J.D. Edwards, Gossypol, a pigment of cottonseed, Chem. Rev. 60 (196') 555-574.[1] R. Adams, T.A. Geissman, J.D. Edwards, Gossypol, a pigment of cottonseed, Chem. Rev. 60 (196') 555-574.

    2. [2] R.E. Royer, L.M. Deck, T.J. Vander Jagt, et al., Synthesis and anti-HIV activity of 1,10-dideoxygossypol and related compounds, J. Med. Chem. 38 (1995) 2427-2432.[2] R.E. Royer, L.M. Deck, T.J. Vander Jagt, et al., Synthesis and anti-HIV activity of 1,10-dideoxygossypol and related compounds, J. Med. Chem. 38 (1995) 2427-2432.

    3. [3] H. Keshmiri-Neghab, B. Goliaei, Therapeutic potential of gossypol: an overview, Pharm. Biol. 52 (2014) 124-128.[3] H. Keshmiri-Neghab, B. Goliaei, Therapeutic potential of gossypol: an overview, Pharm. Biol. 52 (2014) 124-128.

    4. [4] T.S. Lin, R. Schinazi, B.P. Griffith, et al., Selective inhibition of human immunodeficiency virus type 1 replication by the (-) but not the (+) enantiomer of gossypol, Antimicrob. Agents Chemother. 33 (1989) 2149-2151.[4] T.S. Lin, R. Schinazi, B.P. Griffith, et al., Selective inhibition of human immunodeficiency virus type 1 replication by the (-) but not the (+) enantiomer of gossypol, Antimicrob. Agents Chemother. 33 (1989) 2149-2151.

    5. [5] P.A. Keller, C. Brich, S.P. Leach, et al., Novel pharmacophore-based methods reveal gossypol as a reverse transcriptase inhibitor, J. Mol. Graph. Model. 21 (2003) 365-373.[5] P.A. Keller, C. Brich, S.P. Leach, et al., Novel pharmacophore-based methods reveal gossypol as a reverse transcriptase inhibitor, J. Mol. Graph. Model. 21 (2003) 365-373.

    6. [6] T.S. Lin, R.F. Schinazi, J.L. Zhu, et al., Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol, Biochem. Pharmacol. 46 (1993) 251-255.[6] T.S. Lin, R.F. Schinazi, J.L. Zhu, et al., Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol, Biochem. Pharmacol. 46 (1993) 251-255.

    7. [7] J. Yang, F. Zhang, J.R. Li, et al., Synthesis and antiviral activities of novel gossypol derivatives, Bioorg. Med. Chem. Lett. 22 (2012) 1415-1420.[7] J. Yang, F. Zhang, J.R. Li, et al., Synthesis and antiviral activities of novel gossypol derivatives, Bioorg. Med. Chem. Lett. 22 (2012) 1415-1420.

    8. [8] T. An, W.J. Ouyang, W. Pan, et al., Amino acid derivatives of the (-)-enantiomer of gossypol are effective fusion inhibitors of human immunodeficiency virus type 1, Antivir. Res. 94 (2012) 276-287.[8] T. An, W.J. Ouyang, W. Pan, et al., Amino acid derivatives of the (-)-enantiomer of gossypol are effective fusion inhibitors of human immunodeficiency virus type 1, Antivir. Res. 94 (2012) 276-287.

    9. [9] K. Liu, H. Lu, L. Hou, et al., Design, synthesis, and biological evaluation of Ncarboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41, J. Med. Chem. 51 (2008) 7843-7854.[9] K. Liu, H. Lu, L. Hou, et al., Design, synthesis, and biological evaluation of Ncarboxyphenylpyrrole derivatives as potent HIV fusion inhibitors targeting gp41, J. Med. Chem. 51 (2008) 7843-7854.

    10. [10] J. Su, Y. Liu, Z.B. Zheng, et al., Synthesis of aromatic-linked polyamine macrocyclic derivatives as HIV-1 entry inhibitors, Chin. Chem. Lett. 18 (2007) 1166-1168.[10] J. Su, Y. Liu, Z.B. Zheng, et al., Synthesis of aromatic-linked polyamine macrocyclic derivatives as HIV-1 entry inhibitors, Chin. Chem. Lett. 18 (2007) 1166-1168.

    11. [11] J.F. Xu, Z.J. Fang, C.L. Ju, Synthesis of 1, 3, 4, 6-tetra-O-acetyl-β-δ-glucosamine, Chin. J. Synth. Chem. 11 (2003) 379-380, 433.[11] J.F. Xu, Z.J. Fang, C.L. Ju, Synthesis of 1, 3, 4, 6-tetra-O-acetyl-β-δ-glucosamine, Chin. J. Synth. Chem. 11 (2003) 379-380, 433.

    12. [12] Analytical data for compounds: 1: Yellow crystal; 92.9% yield, mp 213-214℃(decomposition); IR (KBr, cm-1): vmax 3483, 3361, 2962, 2928, 1616, 1504, 1369, 1311, 1247, 1092, 1038; 1H NMR (400 MHz, DMSO-δ6): δ 13.1896 (broad, 2H, 2×=CH-NH), 9.7048 (broad, 2H, ×=CH-NH), 8.4878 (s, 2H, 2×6-OH), 7.7589 (s, 2H, 2×Glu-OH), 7.4442 (s, 2H, 2×4-H), 5.3526 (s, 2H, 2×Glu-OH), 5.2442 (s, 2H, 2×Glu-OH), 5.2017 (d, 2H, J=7.8 Hz, 2×Glu-C17HN), 5.0785 (s, 2H, 2×Glu-OH), 3.6644-3.3482 (m, 12H, 2 × 4×Glu-CH, 2×Glu-CH2), 3.1835 (sept, 2H, 2×CH(CH3)2), 1.9323 (s, 6H, 2×Ar-CH3), 1.4344 (d, 12H, J=6.3 Hz, 2×CH(CH3)2); 13C NMR (100 MHz, DMSO-δ6): δ 171.9593, 162.3969, 149.5768, 146.3828, 131.0172, 126.8700, 126.2059, 120.0529, 116.4998, 116.0120, 103.1450, 90.6044, 72.3004, 71.5499, 70.3252, 60.7674, 55.7574, 26.4723, 20.3102, 20.3102, 20.1543; MS (ESI+): m/z 841.8 [M+H]+. 2: Yellow crystal; 92.6% yield, mp 177-178℃; IR (KBr, cm-1):vmax 3485, 2961, 1756, 1610, 1542, 1490, 1418, 1369, 1321, 1216, 1077, 1038; 1H NMR (300 MHz, CDCl3):δ 13.505 (s, 2H, ×=CH-NH), 9.581 (d, 2H, J=9.3 Hz, ×=CH-NH), 7.755 (s, 2H, 2×-OH), 7.599 (s, 2H, 2×4-H), 5.854 (d, 2H, J=7.8 Hz, 2×Glu-C17HN), 5.609 (s, 2H, 2×1-OH), 5.428-3.702(m, 12H, 2×4×Glu-CH, 2×Glu-CH2), 3.592 (sept, 2H, 2×CH(CH3)2), 2.073(s, 24H, 2 × 4×COCH3), 1.958 (s, 6H, 2×Ar-CH3), 1.515 (d, 12H, J=6.3 Hz, 2×CH(CH3)2); 13C NMR(75 MHz, CDCl3):δ 173.64, 170.57, 169.88, 169.63, 168.71, 162.49, 149.16, 146.80, 132.36, 129.49, 128.40, 118.53, 115.98, 114.22, 104.15, 92.07, 72.68, 72.33, 67.71, 63.99, 61.48, 27.43, 20.79, 20.65, 20.59, 20.46, 20.24, 20.19, 19.96; MS (ESI+): m/z 1176.1 [M-H]-. 3: Yellow crystal; 88.2% yield, mp 210℃(decomposition); IR (KBr, cm-1):vmax 3483, 3377, 2963, 2871, 1616, 1520, 1494, 1401, 1308, 1246, 1168, 1021; 1HNMR(400 MHz, DMSOd6):δ13.2702 (s, 2H, 2×=CH-NH), 9.6983 (s, 2H, ×=CH-NH), 8.3898 (s, 2H, 2×-OH), 8.1827 (m, 2H, 2×N19-H), 7.3605 (s, 2H, 2×4-H), 4.4452 (m, 4H, 2×20-H), 3.6750 (m, 2H, 2×C17HN), 3.5397 (sept, 2H, 2×CH(CH3)2), 1.9473 (d, 6H, J=5.5 Hz, 2×17-CH3), 1.8841 (s, 6H, 2×Ar-CH3), 1.4247 (d, 12H, J=6.3 Hz, 2×CH(CH3)2); 13C NMR (100 MHz, DMSO-δ6):δ177.8820, 177.4359, 175.0255, 157.9823, 151.4497, 145.2643, 132.0330, 128.6840, 127.1184, 121.3668, 117.6309, 116.2757, 103.4103, 61.2516, 48.2834, 26.8479, 25.5420, 25.5420, 25.2018, 23.7551; MS (ESI+): m/z 773.8 [[M-2Na+H]-2Na+H]-. 4: Yellow crystal; 85.3% yield, mp 237℃(decomposition); IR (KBr, cm-1):vmax 3483, 3371, 2973, 2932, 2871, 1614, 1520, 1453, 1407, 1365, 1309, 1244, 1168, 1056; 1H NMR (400 MHz, DMSO-δ6):δ13.2743 (s, 2H,5CH-NH), 10.0064 (s, 2H, ×=CH-NH), 8.2501 (s, 2H, 2×=5OH), 8.1609 (d, 2H, J=6.5 Hz, 2×N19-H), 7.3257 (s, 2H, 2×4-H), 4.4312 (m, 2H, 2×20-H), 3.9447 (m, 2H, 2×C17HN), 3.6738 (sept, 2H, 2×CH(CH3)2), 1.9384 (d, 6H, J=5.5 Hz, 2×20-CH3), 1.8869 (s, 6H, 2×Ar-CH3), 1.4259 (d, 12H, J=6.2 Hz, 2×CH(CH3)2), 1.1897 (d, 6H, J=5.5 Hz, 2×17-CH3); 13C NMR (100 MHz, DMSOd6):δ174.9651, 172.5518, 169.2470, 160.3944, 150.9108, 146.1267, 131.1563, 126.7315, 126.5257, 121.0936, 116.4858, 116.0166, 103.7602, 55.9979, 49.4534, 26.4918, 20.3004, 20.3004, 20.0538, 18.6808, 18.5059; MS (ESI+): m/z 801.9[M-2Na+H]-. 5: Yellow crystal; 90.8% yield, mp 255℃(decomposition); IR (KBr, cm-1):vmax 3483, 3356, 2968, 2871, 1609, 1520, 1453, 1405, 1364, 1313, 1242. 1H NMR (400 MHz, DMSO-δ6):δ13.2983 (s, 2H, ×=CH-NH), 9.8831 (s, 2H, ×=CH-NH), 8.5003 (s, 2H, 2×-OH), 8.3374 (d, 2H, J=7.5 Hz, 2×N19-H), 7.3494 (s, 2H, 2×4-H), 4.4792 (m, 2H, 2×20-H), 3.9668 (m, 2H, 2×C17HN), 3.6590 (sept, 2H, CH(CH3)2), 2.6711 (s, 2H, 2×23a-H), 2.6079 (s, 2H, 2×23b-H), 1.9081 (s, 6H, 2×Ar-CH3), 1.4091 (d, 12H, J=6.3 Hz, 2×CH(CH3)2), 3)2), 1.1654 (d, 6H, J=6.8 Hz, 2 × 20-CH3); MS (ESI+): m/z 886.8 [M-4Na]-. 6: Yellow crystal; 86.6% yield, mp 200℃(decomposition); IR (KBr, cm-1):vmax 3488, 3378, 2960, 1665, 1613, 1519, 1496, 1452, 1396, 1309, 1244, 1173, 1027; 1H NMR (400 MHz, DMSO-d6):δ 13.1768 (s, 2H, ×=CH-NH), 9.8977 (s, 2H, ×=CH-NH), 8.4118 (s, 2H, 2×-OH), 8.1870 (d, 2H, J=7.6 Hz, 2×N19-H), 7.4019 (s, 2H, 2×4-H), 7.0479 (m, 4H, 2×25-H, 2×27-H), 6.9959 (m, 4H, 2×24-H, 2×28-H), 6.9116 (m, 2H, 2×26-H), 4.3655 (m, 2H, 2×20-H), 4.1789 (m, 2H, 2×C17HN), 3.6901 (sept, 2H, 2×CH(CH3)2), 3.0095 (s, 2H, 2×22a-H), 2.7714 (s, 2H, 2×22b-H), 1.9433 (s, 6H, 2×Ar-CH3), 1.4417 (d, 12H, J=6.2 Hz, 2×CH(CH3)2), 1.3624(d, 6H, J=6.5 Hz, 2×17-CH3); 13C NMR (100 MHz, DMSO-d6):δ175.2311, 173.4149, 169.3054, 160.3966, 150.1252, 146.1848, 138.4853, 129.3677, 129.3677, 129.2596, 129.2596, 127.7315, 131.1251, 126.6372, 125.6573, 122.1602, 118.6773, 116.5517, 103.6638, 57.3238, 55.1120, 37.2806, 26.4901, 20.2914, 20.2914, 19.6090, 19.5816; MS (ESI+):m/z 954.0 [M-2Na+H]-. 7: Brown crystal; 88.7% yield, mp 201℃(decomposition); IR (KBr, cm-1):vmax 3483, 3317, 2964, 1617, 1538, 1399, 1312, 1245, 1168, 1028; 1H NMR (400 MHz, DMSO-δ6):δ12.9935 (s, 2H, ×=CH-NH), 9.9501 (s, 2H, ×=CH-NH), 8.8190 (m, 2H, 2×N19-H), 8.4218 (s, 2H, 2×-OH), 7.6883 (m, 2H, 2×N22-H), 7.3458 (s, 2H, 2×4-H), 4.3017 (m, 4H, 2×20-H), 3.7871 (m, 4H, 2×23-H), 3.7077 (m, 4H, 2×C17H2N), 3.6791 (sept, 2H, 2×CH(CH3)2), 1.9421 (s, 6H, 2×Ar-CH3), 1.4308 (d, 12H, J=7.0 Hz, 2×CH(CH3)2); MS (ESI+): m/z 859.8 [[M-2Na+H]-2Na+H] . 8: Brown crystal; 87.4% yield, mp 233℃(decomposition); IR (KBr, cm-1):vmax 3483, 3364, 2977, 1613, 1521, 1453, 1406, 1364, 1309, 1244, 1168, 1104, 1057, 1025; 1HNMR (400 MHz, DMSO-d6):δ13.2814 (s, 2H, ×=CH-NH), 9.9811 (s, 2H, ×=CH-NH), 8.7155 (d, 2H, J=7.6 Hz, 2×N19H), 8.4064 (s, 2H, 2×-OH), 7.7190 (d, 2H, J=6.8 Hz, 2×N22H), 7.3609 (s, 2H, 2×4-H), 4.3606 (m, 2H, 2×20-H), 4.2436 (m, 2H, 2×23-H), 3.8355 (m, 2H, 2×C17HN), 3.6803 (sept, 2H, 2×CH(CH3)2), 1.9385 (s, 6H, 2×Ar-CH3), 1.4989 (d, 6H, J=6.3 Hz, 2×20-CH3), 1.4301 (d, 12H, J=6.3 Hz, 2×CH(CH3)2), 1.2282 (d, 6H, J=6.2 Hz, 2×23-CH3), 1.1751 (d, 6H, J=6.3 Hz, 2×17-CH3); 13CNMR (100 MHz, DMSO-d6):δ174.9121, 170.6384, 172.2762, 170.1312, 160.4444, 149.2146, 146.0314, 131.1066, 126.8046, 126.4187, 121.9770, 117.0177, 116.0765, 103.8738, 55.9931, 49.0865, 48.5153, 26.4920, 20.2776, 20.2776, 20.0402, 18.6090, 18.5126, 17.9255; MS (ESI+): m/z 944.0 [[M-2Na+H]-2Na+H]-.[12] Analytical data for compounds: 1: Yellow crystal; 92.9% yield, mp 213-214℃(decomposition); IR (KBr, cm-1): vmax 3483, 3361, 2962, 2928, 1616, 1504, 1369, 1311, 1247, 1092, 1038; 1H NMR (400 MHz, DMSO-δ6): δ 13.1896 (broad, 2H, 2×=CH-NH), 9.7048 (broad, 2H, ×=CH-NH), 8.4878 (s, 2H, 2×6-OH), 7.7589 (s, 2H, 2×Glu-OH), 7.4442 (s, 2H, 2×4-H), 5.3526 (s, 2H, 2×Glu-OH), 5.2442 (s, 2H, 2×Glu-OH), 5.2017 (d, 2H, J=7.8 Hz, 2×Glu-C17HN), 5.0785 (s, 2H, 2×Glu-OH), 3.6644-3.3482 (m, 12H, 2 × 4×Glu-CH, 2×Glu-CH2), 3.1835 (sept, 2H, 2×CH(CH3)2), 1.9323 (s, 6H, 2×Ar-CH3), 1.4344 (d, 12H, J=6.3 Hz, 2×CH(CH3)2); 13C NMR (100 MHz, DMSO-δ6): δ 171.9593, 162.3969, 149.5768, 146.3828, 131.0172, 126.8700, 126.2059, 120.0529, 116.4998, 116.0120, 103.1450, 90.6044, 72.3004, 71.5499, 70.3252, 60.7674, 55.7574, 26.4723, 20.3102, 20.3102, 20.1543; MS (ESI+): m/z 841.8 [M+H]+. 2: Yellow crystal; 92.6% yield, mp 177-178℃; IR (KBr, cm-1):vmax 3485, 2961, 1756, 1610, 1542, 1490, 1418, 1369, 1321, 1216, 1077, 1038; 1H NMR (300 MHz, CDCl3):δ 13.505 (s, 2H, ×=CH-NH), 9.581 (d, 2H, J=9.3 Hz, ×=CH-NH), 7.755 (s, 2H, 2×-OH), 7.599 (s, 2H, 2×4-H), 5.854 (d, 2H, J=7.8 Hz, 2×Glu-C17HN), 5.609 (s, 2H, 2×1-OH), 5.428-3.702(m, 12H, 2×4×Glu-CH, 2×Glu-CH2), 3.592 (sept, 2H, 2×CH(CH3)2), 2.073(s, 24H, 2 × 4×COCH3), 1.958 (s, 6H, 2×Ar-CH3), 1.515 (d, 12H, J=6.3 Hz, 2×CH(CH3)2); 13C NMR(75 MHz, CDCl3):δ 173.64, 170.57, 169.88, 169.63, 168.71, 162.49, 149.16, 146.80, 132.36, 129.49, 128.40, 118.53, 115.98, 114.22, 104.15, 92.07, 72.68, 72.33, 67.71, 63.99, 61.48, 27.43, 20.79, 20.65, 20.59, 20.46, 20.24, 20.19, 19.96; MS (ESI+): m/z 1176.1 [M-H]-. 3: Yellow crystal; 88.2% yield, mp 210℃(decomposition); IR (KBr, cm-1):vmax 3483, 3377, 2963, 2871, 1616, 1520, 1494, 1401, 1308, 1246, 1168, 1021; 1HNMR(400 MHz, DMSOd6):δ13.2702 (s, 2H, 2×=CH-NH), 9.6983 (s, 2H, ×=CH-NH), 8.3898 (s, 2H, 2×-OH), 8.1827 (m, 2H, 2×N19-H), 7.3605 (s, 2H, 2×4-H), 4.4452 (m, 4H, 2×20-H), 3.6750 (m, 2H, 2×C17HN), 3.5397 (sept, 2H, 2×CH(CH3)2), 1.9473 (d, 6H, J=5.5 Hz, 2×17-CH3), 1.8841 (s, 6H, 2×Ar-CH3), 1.4247 (d, 12H, J=6.3 Hz, 2×CH(CH3)2); 13C NMR (100 MHz, DMSO-δ6):δ177.8820, 177.4359, 175.0255, 157.9823, 151.4497, 145.2643, 132.0330, 128.6840, 127.1184, 121.3668, 117.6309, 116.2757, 103.4103, 61.2516, 48.2834, 26.8479, 25.5420, 25.5420, 25.2018, 23.7551; MS (ESI+): m/z 773.8 [[M-2Na+H]-2Na+H]-. 4: Yellow crystal; 85.3% yield, mp 237℃(decomposition); IR (KBr, cm-1):vmax 3483, 3371, 2973, 2932, 2871, 1614, 1520, 1453, 1407, 1365, 1309, 1244, 1168, 1056; 1H NMR (400 MHz, DMSO-δ6):δ13.2743 (s, 2H,5CH-NH), 10.0064 (s, 2H, ×=CH-NH), 8.2501 (s, 2H, 2×=5OH), 8.1609 (d, 2H, J=6.5 Hz, 2×N19-H), 7.3257 (s, 2H, 2×4-H), 4.4312 (m, 2H, 2×20-H), 3.9447 (m, 2H, 2×C17HN), 3.6738 (sept, 2H, 2×CH(CH3)2), 1.9384 (d, 6H, J=5.5 Hz, 2×20-CH3), 1.8869 (s, 6H, 2×Ar-CH3), 1.4259 (d, 12H, J=6.2 Hz, 2×CH(CH3)2), 1.1897 (d, 6H, J=5.5 Hz, 2×17-CH3); 13C NMR (100 MHz, DMSOd6):δ174.9651, 172.5518, 169.2470, 160.3944, 150.9108, 146.1267, 131.1563, 126.7315, 126.5257, 121.0936, 116.4858, 116.0166, 103.7602, 55.9979, 49.4534, 26.4918, 20.3004, 20.3004, 20.0538, 18.6808, 18.5059; MS (ESI+): m/z 801.9[M-2Na+H]-. 5: Yellow crystal; 90.8% yield, mp 255℃(decomposition); IR (KBr, cm-1):vmax 3483, 3356, 2968, 2871, 1609, 1520, 1453, 1405, 1364, 1313, 1242. 1H NMR (400 MHz, DMSO-δ6):δ13.2983 (s, 2H, ×=CH-NH), 9.8831 (s, 2H, ×=CH-NH), 8.5003 (s, 2H, 2×-OH), 8.3374 (d, 2H, J=7.5 Hz, 2×N19-H), 7.3494 (s, 2H, 2×4-H), 4.4792 (m, 2H, 2×20-H), 3.9668 (m, 2H, 2×C17HN), 3.6590 (sept, 2H, CH(CH3)2), 2.6711 (s, 2H, 2×23a-H), 2.6079 (s, 2H, 2×23b-H), 1.9081 (s, 6H, 2×Ar-CH3), 1.4091 (d, 12H, J=6.3 Hz, 2×CH(CH3)2), 3)2), 1.1654 (d, 6H, J=6.8 Hz, 2 × 20-CH3); MS (ESI+): m/z 886.8 [M-4Na]-. 6: Yellow crystal; 86.6% yield, mp 200℃(decomposition); IR (KBr, cm-1):vmax 3488, 3378, 2960, 1665, 1613, 1519, 1496, 1452, 1396, 1309, 1244, 1173, 1027; 1H NMR (400 MHz, DMSO-d6):δ 13.1768 (s, 2H, ×=CH-NH), 9.8977 (s, 2H, ×=CH-NH), 8.4118 (s, 2H, 2×-OH), 8.1870 (d, 2H, J=7.6 Hz, 2×N19-H), 7.4019 (s, 2H, 2×4-H), 7.0479 (m, 4H, 2×25-H, 2×27-H), 6.9959 (m, 4H, 2×24-H, 2×28-H), 6.9116 (m, 2H, 2×26-H), 4.3655 (m, 2H, 2×20-H), 4.1789 (m, 2H, 2×C17HN), 3.6901 (sept, 2H, 2×CH(CH3)2), 3.0095 (s, 2H, 2×22a-H), 2.7714 (s, 2H, 2×22b-H), 1.9433 (s, 6H, 2×Ar-CH3), 1.4417 (d, 12H, J=6.2 Hz, 2×CH(CH3)2), 1.3624(d, 6H, J=6.5 Hz, 2×17-CH3); 13C NMR (100 MHz, DMSO-d6):δ175.2311, 173.4149, 169.3054, 160.3966, 150.1252, 146.1848, 138.4853, 129.3677, 129.3677, 129.2596, 129.2596, 127.7315, 131.1251, 126.6372, 125.6573, 122.1602, 118.6773, 116.5517, 103.6638, 57.3238, 55.1120, 37.2806, 26.4901, 20.2914, 20.2914, 19.6090, 19.5816; MS (ESI+):m/z 954.0 [M-2Na+H]-. 7: Brown crystal; 88.7% yield, mp 201℃(decomposition); IR (KBr, cm-1):vmax 3483, 3317, 2964, 1617, 1538, 1399, 1312, 1245, 1168, 1028; 1H NMR (400 MHz, DMSO-δ6):δ12.9935 (s, 2H, ×=CH-NH), 9.9501 (s, 2H, ×=CH-NH), 8.8190 (m, 2H, 2×N19-H), 8.4218 (s, 2H, 2×-OH), 7.6883 (m, 2H, 2×N22-H), 7.3458 (s, 2H, 2×4-H), 4.3017 (m, 4H, 2×20-H), 3.7871 (m, 4H, 2×23-H), 3.7077 (m, 4H, 2×C17H2N), 3.6791 (sept, 2H, 2×CH(CH3)2), 1.9421 (s, 6H, 2×Ar-CH3), 1.4308 (d, 12H, J=7.0 Hz, 2×CH(CH3)2); MS (ESI+): m/z 859.8 [[M-2Na+H]-2Na+H] . 8: Brown crystal; 87.4% yield, mp 233℃(decomposition); IR (KBr, cm-1):vmax 3483, 3364, 2977, 1613, 1521, 1453, 1406, 1364, 1309, 1244, 1168, 1104, 1057, 1025; 1HNMR (400 MHz, DMSO-d6):δ13.2814 (s, 2H, ×=CH-NH), 9.9811 (s, 2H, ×=CH-NH), 8.7155 (d, 2H, J=7.6 Hz, 2×N19H), 8.4064 (s, 2H, 2×-OH), 7.7190 (d, 2H, J=6.8 Hz, 2×N22H), 7.3609 (s, 2H, 2×4-H), 4.3606 (m, 2H, 2×20-H), 4.2436 (m, 2H, 2×23-H), 3.8355 (m, 2H, 2×C17HN), 3.6803 (sept, 2H, 2×CH(CH3)2), 1.9385 (s, 6H, 2×Ar-CH3), 1.4989 (d, 6H, J=6.3 Hz, 2×20-CH3), 1.4301 (d, 12H, J=6.3 Hz, 2×CH(CH3)2), 1.2282 (d, 6H, J=6.2 Hz, 2×23-CH3), 1.1751 (d, 6H, J=6.3 Hz, 2×17-CH3); 13CNMR (100 MHz, DMSO-d6):δ174.9121, 170.6384, 172.2762, 170.1312, 160.4444, 149.2146, 146.0314, 131.1066, 126.8046, 126.4187, 121.9770, 117.0177, 116.0765, 103.8738, 55.9931, 49.0865, 48.5153, 26.4920, 20.2776, 20.2776, 20.0402, 18.6090, 18.5126, 17.9255; MS (ESI+): m/z 944.0 [[M-2Na+H]-2Na+H]-.

    13. [13] J. Yang, Z.H. Jing, J.J. Jie, P. Guo, Fluorescence spectroscopy study on the interaction between gossypol and bovine serum albumin, J. Mol. Struct. 920 (2009) 227-230.[13] J. Yang, Z.H. Jing, J.J. Jie, P. Guo, Fluorescence spectroscopy study on the interaction between gossypol and bovine serum albumin, J. Mol. Struct. 920 (2009) 227-230.

    14. [14] B.D. Welch, A.P. VanDemark, A. Heroux, C.P. Hill, M.S. Kay, Potent D-peptide inhibitors of HIV-1 entry, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 16828-16833.[14] B.D. Welch, A.P. VanDemark, A. Heroux, C.P. Hill, M.S. Kay, Potent D-peptide inhibitors of HIV-1 entry, Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 16828-16833.

    15. [15] G.Y. Zhou, S.D. Chu, Discovery of small molecule fusion inhibitors targeting HIV-1 gp41, Curr. Pharm. Des. 19 (2013) 1818-1826.[15] G.Y. Zhou, S.D. Chu, Discovery of small molecule fusion inhibitors targeting HIV-1 gp41, Curr. Pharm. Des. 19 (2013) 1818-1826.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  1412
  • HTML全文浏览量:  22
文章相关
  • 收稿日期:  2014-02-20
  • 网络出版日期:  2014-05-13
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