Journal of the Korean Chemical Society (대한화학회지)

Korean Chemical Society (대한화학회)
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Chemical Reactivity and Biological Activities for Tricyclic Enediyne Compound Possessing Fluorine

플루오르를 가진 삼중고리 Enediyne 화합물에 대한 화학적 반응성과 생물학적 활성

  • Published : 2004.08.20
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Abstract

Keywords

EXPERIMENTAL SECTION

Genenral Techniques. NMR spectra were recorded on a Bruker DPX-300 or 500 instrument. All reactions were monitored by thin-layer chromatography carried out on 0.25 mm E. Merck silica gel plates (60F-254) under UV light. All new compounds were identified by spectroscopic methods.

Synthesis of compound 4. To a suspension of NaH (38.9 mg of 60% dispersion in mineral oil, 0.97 mmol) in dry THF (2 mL) was added 2-(phenylthio) ethanol (0.13 mL, 0.97 mmol) followed by stirring at 25 ℃ for 5 min. The resulting solution was added to a solution of 2 (200 mg, 0.49 mmol) in dry THF (4 mL). After stirring at 25 ℃ for 10 min, the reaction mixture was diluted with ethyl ether (20 mL), poured into H2O (50 mL), and extracted with ethyl ether (2×20 mL). The combined organic layers were dried (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography (silica gel, 25% ethyl ether in hexane) to give the product 4 in quantitative yield. Rf= 0.45 (silica gel, 25% ethyl ether in hexane); 1H NMR (300 MHz, DMSO-d6): δ 7.68 (dd, J = 8.8, 6.2 Hz, 1H, aromatic), 7.38-7.23 (m, 3H, aromatic), 7.21-7.09 (m, 2H, aromatic), 7.17 (td, J = 8.6, 2.7 Hz, 1H, aromatic), 6.74-6.69 (m, 1H, aromatic), 5.98 (dd, J = 9.9, 1.4Hz, 1H, olefinic), 5.86 (dd, J = 9.9, 1.4 Hz, 1H, olefinic), 5.35 (br s, 1H, CHN), 4.31-4.25 (m, 1H, CH2O), 4.28-4.15 (m, 1H, CH2O), 3.97 (br s, 1H, CH2CH), 3.33-3.23 (m, 2H, SCH2), 2.26-2.19 (m, 1H, CH2), 2.07-1.98 (m, 1H, CH2), 1.79-1.63 (m, 3H, CH2), 1.54-1.45 (m, 1H, CH2); 13C NMR (75 MHz, DMSOd6): δ 161.2 (1JCF=244 Hz), 153.2, 135.0, 129.3, 129.2, 128.5, 126.1, 125.8, 122.3, 119.5, 118.7, 112.5(2JCF=21 Hz), 111.8 (2JCF=21 Hz), 102.3, 93.7, 91.0, 88.7, 69.6, 67.9, 64.6, 60.1, 48.7, 28.6, 22.8, 22.2, 15.2.

Synthesis of compound 5. To a solution of 4(186 mg, 0.40 mmol) in dichloromethane (2.6 mL) and saturated aqueous sodium bicarbonate (2.6 mL) was added mCPBA (70%, 243 mg, 0.99 mmol) followed by stirring at 0 ℃ for 10 min. The reaction mixture was poured into saturated aqueous sodium bicarbonate (15 mL) and extracted with dichloromethane (2×15 mL). The combined organic layers were dryed (Na2SO4) and evaporated in vacuo. The residue was purified by column chromatography (silica gel, 75% ethyl ether in petroleum ether) to provide 5 (119 mg, 60%). Rf= 0.38 (silica gel, 75% ethyl ether in hexane); 1H NMR (500 MHz, DMSO-d6): δ 7.90 (d, J=7.6 Hz, 2H, aromatic), 7.75-7.69 (m, 2H, aromatic), 7.63 (t, J=7.6 Hz, 2H, aromatic), 7.17 (dd, J=10.6, 2.7 Hz, 1H, aromatic), 7.06 (td, J=8.5, 2.7 Hz, 1H, aromatic), 6.01 (dd, J=9.9, 1.7 Hz, 1H, olefinic), 5.90 (dd, J=9.9, 1.7 Hz, 1H, olefinic), 5.20 (br s, 1H, CHN), 4.43 (m, 1H, CH2O), 4.34 (m, 1H, CH2O), 4.00 (br s, 1H, CH2CH), 3.82-3.78 (m, 2H, SO2CH2), 2.25-2.20 (m, 1H, CH2), 2.10-2.05 (m, 1H, CH2), 1.82-1.78 (m, 1H, CH2), 1.75-1.69 (m, 2H, CH2), 1.55-1.51 (m, 1H, CH2); 13C NMR (75 MHz, DMSO-d6): δ 161.2 (1JCF = 244Hz), 152.6, 139.0, 134.1, 129.5, 129.2, 128.3, 127.5, 125.8, 124.5, 122.3, 112.6 (2JCF= 25 Hz), 111.8 (2JCF=25 Hz), 102.3, 93.5, 91.0, 88.7, 69.5, 60.6, 59.9, 53.8, 48.7, 28.6, 22.6, 22.1, 15.2.

Synthesis of free amine 7. To a solution of enediyne 5 (20 mg, 0.04 mmol) in benzene (1.5 mL) was added DBU (12 mL, 0.08 mmol) at 20 ℃. The reaction progress was monitored at a proper interval by TLC. When the reaction was completed the solution was concentrated in vacuo. The residue was purified by column chromatography (silica gel, 75% ethyl ether in hexane containing 1% triethylamine) to give the amine 7 (7.8 mg, 69%). Rf = 0.75 (silica gel, 75% ethyl ether in hexane); 1H NMR (300MHz, DMSO-d6): δ 7.49 (dd, J=8.6, 6.4 Hz, 1H, aromatic), 6.61 (d, J=2.9 Hz, 1H, NH), 6.44 (td, J=8.6, 2.6 Hz, 1H, aromatic), 6.35 (dd, J=11.0, 2.6 Hz, 1H, aromatic), 5.97 (s, 2H, olefinic), 4.29(br s, 1H, NCH), 3.90 (br s, 1H, CH2CH), 2.14 (dd, J=16.1, 7.1, 1H, CH2), 2.01-1.88 (m, 1H, CH2), 1.78-1.55 (m, 3H, CH2), 1.51-1.40 (m, 1H, CH2); 13C NMR (75.5 MHz, DMSO-d6): δ 162.5 (1JCF = 240 Hz), 145.2, 139.5, 131.5, 124.2, 123.2, 103.7(2JCF=22 Hz), 103.1, 101.2 (2JCF=25 Hz), 98.1, 90.3, 86.7, 69.5, 60.0, 47.4, 28.4, 23.6, 23.4, 15.3.

Synthesis of free amine 8. Compound 8 was prepared from enediyne 6 in 54% yield in a same manner as described for 7. Rf = 0.75 (silica gel, 75% ethyl ether in hexane); 1H NMR (300MHz, DMSOd6): δ 7.43 (br d, J=7.7 Hz, 1H, aromatic), 6.99 (td, J=8.5, 1.3 Hz, 1H, aromatic), 6.61 (td, J=8.5, 1.1Hz, 1H, aromatic), 6.53 (br d, J=8.0 Hz, 1H, aromatic), 6.22 (d, J=2.8 Hz, 1H, NH), 5.89 (s, 2H, olefinic), 4.19 (br s, 1H, NCH), 3.86 (br s, 1H, CH2CH), 2.14 (dd, J=15.4, 6.9, 1H, CH2), 2.00-1.89 (m, 1H, H2), 1.80-1.61 (m, 3H, H2); 1.47-1.40 (m, 1H, H2); 13C NMR (75.5 MHz, DMSO-d6): δ 143.2, 128.3, 126.8, 124.0, 123.1, 121.1, 117.1, 114.9, 103.2, 98.6, 90.2, 86.6, 69.8, 60.3, 47.6, 28.2, 23.7, 23.4, 15.3.

Cycloaromatization of the intermediate 7. To a solution of amine 7 (7.8 mg, 0.027 mmol) in wet benzene (1.5 mL) and 1,4-cyclohexadiene (0.5 mL) was added a catalytic amount of silica gel at 20 ℃. After 40 min, the reaction was completed and the solution was concentrated in vacuo. The residue was purified by column chromatography (silica gel, 67% ethyl ether in hexane) to give the diol 9 (4.0mg, 48%). Rf = 0.35 (silica, 67% ethyl ether in hexane); 1H NMR (500MHz, CDCl3): δ 7.92 (d, J=7.5Hz, 1H, aromatic), 7.60-7.54 (m, 2H, aromatic), 7.19-7.14 (m, 1H, aromatic), 6.92 (d, J=7.3 Hz, 1H, aromatic), 6.61 (td, J=8.5, 2.4 Hz, 1H, aromatic), 6.51 (td, J=8.5, 2.4 Hz, 1H, aromatic), 4.32 (br s, 1H, NCH), 4.28-4.15 (br, 1H, NH), 4.16 (s, 1H, OH), 3.55 (br s, 1H, CH2CH), 2.75 (s, 1H, OH), 2.49 (td, J=13.6, 6.3 Hz, 1H, CH2), 2.32 (dt, J=13.6, 3.6 Hz, 1H, CH2), 2.25 (td, J=14.1, 6.3 Hz, 1H, CH2), 1.84 (dd, J=13.8, 5.2 Hz, 1H, CH2), 1.70 (dd, J=13.8, 5.2 Hz, 1H, CH2), 1.47-1.44 (m, 1H, CH2; 13C NMR (75.5 MHz, DMSO-d6): δ 163.3 (1JCF=244 Hz), 139.1, 134.3, 130.0, 129.4, 128.9, 127.6, 127.5, 127.4, 126.2, 108.1 (2JCF=22 Hz), 102.2 (2JCF=25 Hz), 73.1, 63.2, 52.8, 32.6, 30.4, 27.8, 19.0.

References

  1. Konishi, M.; Ohkuma, H.; Matsumoto, K.; Tsuno, T.; Kamei, H.; Miyaki, T.; Oki, T.; Kawaguchi, H.; VanDuyne, G. D.; Clardy, J. J. Antibot. 1989, 42, 1449. https://doi.org/10.7164/antibiotics.42.1449
  2. Konishi, M.; Ohkuma, H.; Tsuno, T.; Oki, T.; VanDuyne, G. D.; Clardy, J. J. Am. Chem. Soc. 1990, 112, 3715. https://doi.org/10.1021/ja00165a097
  3. Langley, D. R.; Doyle, T. W.; Beverridge, D. L. J. Am. Chem. Soc. 1991, 113, 3495. https://doi.org/10.1021/ja00009a040
  4. Sugiura, Y.; Shiraki, T.; Konishi, M.; Oki, T. Proc. Natl. Acad. Sci. U.S.A. 1990, 87, 3831. https://doi.org/10.1073/pnas.87.10.3831
  5. Nicolaou, K. C.; Smith, A. L.; Wendeborn, S. V.; Hwang, C.-K. J. Am. Chem. Soc. 1991, 113, 3106. https://doi.org/10.1021/ja00008a045
  6. Bergman, R. G. Acc. Chem. Res. 1973, 6, 25. https://doi.org/10.1021/ar50061a004
  7. Jones, R. R.; Bergman, R. G. J. Am. Chem. Soc. 1972, 94, 660. https://doi.org/10.1021/ja00757a071
  8. Kim, J. H.; Ryoo, K. S.; Choi. J.-H.; Hong, Y. P. Bull. Korean Chem. Soc. 2000, 21, 37.
  9. Nicolaou, K. C.; Dai, W.-M.; Hong, Y. P.; Tsay, S.-C.; Baldridge, K. K.; Siegel, J. S. J. Am. Chem. Soc. 1993, 115, 7944. https://doi.org/10.1021/ja00071a003
  10. Hong, Y. P.; Woo, L. Bull. Korean Chem. Soc. 1997, 18, 229.
  11. Hong, Y. P.; Woo, L. J. Korean Chem. Soc., 1998, 42, 467.

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