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Chemical Reactivity and Biological Activities for Tricyclic Enediyne Compound Possessing Fluorine
Chemical Reactivity and Biological Activities for Tricyclic Enediyne Compound Possessing Fluorine
Journal of the Korean Chemical Society. 2004. Aug, 48(4): 447-450
Copyright © 2004, The Korean Chemical Society
  • Received : March 15, 2004
  • Published : August 20, 2004
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용표 홍
건상 유
종하 최

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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 H 2 O (50 mL), and extracted with ethyl ether (2×20 mL). The combined organic layers were dried (Na 2 SO 4 ) 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. R f = 0.45 (silica gel, 25% ethyl ether in hexane); 1 H NMR (300 MHz, DMSO-d 6 ): 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, CH N), 4.31-4.25 (m, 1H, CH 2 O), 4.28-4.15 (m, 1H, CH 2 O), 3.97 (br s, 1H, CH 2 CH ), 3.33-3.23 (m, 2H, S CH 2 ), 2.26-2.19 (m, 1H, CH 2 ), 2.07-1.98 (m, 1H, CH 2 ), 1.79-1.63 (m, 3H, CH 2 ), 1.54-1.45 (m, 1H, CH 2 ); 13 C NMR (75 MHz, DMSOd 6 ): δ 161.2 ( 1 J CF =244 Hz), 153.2, 135.0, 129.3, 129.2, 128.5, 126.1, 125.8, 122.3, 119.5, 118.7, 112.5( 2 J CF =21 Hz), 111.8 ( 2 J CF =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 m CPBA (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 (Na 2 SO 4 ) 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%). R f = 0.38 (silica gel, 75% ethyl ether in hexane); 1 H NMR (500 MHz, DMSO-d 6 ): 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, CH N), 4.43 (m, 1H, CH 2 O), 4.34 (m, 1H, C H 2 O), 4.00 (br s, 1H, CH 2 CH ), 3.82-3.78 (m, 2H, SO 2 C H 2 ), 2.25-2.20 (m, 1H, CH 2 ), 2.10-2.05 (m, 1H, CH 2 ), 1.82-1.78 (m, 1H, CH 2 ), 1.75-1.69 (m, 2H, CH 2 ), 1.55-1.51 (m, 1H, CH 2 ); 13 C NMR (75 MHz, DMSO-d 6 ): δ 161.2 ( 1 J CF = 244Hz), 152.6, 139.0, 134.1, 129.5, 129.2, 128.3, 127.5, 125.8, 124.5, 122.3, 112.6 ( 2 J CF = 25 Hz), 111.8 ( 2 J CF =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%). R f = 0.75 (silica gel, 75% ethyl ether in hexane); 1 H NMR (300MHz, DMSO-d 6 ): δ 7.49 (dd, J =8.6, 6.4 Hz, 1H, aromatic), 6.61 (d, J =2.9 Hz, 1H, N H ), 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, NC H ), 3.90 (br s, 1H, CH 2 CH ), 2.14 (dd, J =16.1, 7.1, 1H, C H 2 ), 2.01-1.88 (m, 1H, C H 2 ), 1.78-1.55 (m, 3H, C H 2 ), 1.51-1.40 (m, 1H, C H 2 ); 13 C NMR (75.5 MHz, DMSO-d 6 ): δ 162.5 ( 1 J CF = 240 Hz), 145.2, 139.5, 131.5, 124.2, 123.2, 103.7( 2 J CF =22 Hz), 103.1, 101.2 ( 2 J CF =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 . R f = 0.75 (silica gel, 75% ethyl ether in hexane); 1 H NMR (300MHz, DMSOd 6 ): 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, N H ), 5.89 (s, 2H, olefinic), 4.19 (br s, 1H, NC H ), 3.86 (br s, 1H, CH 2 C H ), 2.14 (dd, J =15.4, 6.9, 1H, C H 2 ), 2.00-1.89 (m, 1H, H 2 ), 1.80-1.61 (m, 3H, H 2 ); 1.47-1.40 (m, 1H, H 2 ); 13 C NMR (75.5 MHz, DMSO-d 6 ): 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%). R f = 0.35 (silica, 67% ethyl ether in hexane); 1 H 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, NC H ), 4.28-4.15 (br, 1H, N H ), 4.16 (s, 1H, O H ), 3.55 (br s, 1H, CH 2 C H ), 2.75 (s, 1H, O H ), 2.49 (td, J =13.6, 6.3 Hz, 1H, CH 2 ), 2.32 (dt, J =13.6, 3.6 Hz, 1H, CH 2 ), 2.25 (td, J =14.1, 6.3 Hz, 1H, CH 2 ), 1.84 (dd, J =13.8, 5.2 Hz, 1H, CH 2 ), 1.70 (dd, J =13.8, 5.2 Hz, 1H, CH 2 ), 1.47-1.44 (m, 1H, CH 2 ; 13 C NMR (75.5 MHz, DMSO-d 6 ): δ 163.3 ( 1 J CF =244 Hz), 139.1, 134.3, 130.0, 129.4, 128.9, 127.6, 127.5, 127.4, 126.2, 108.1 ( 2 J CF =22 Hz), 102.2 ( 2 J CF =25 Hz), 73.1, 63.2, 52.8, 32.6, 30.4, 27.8, 19.0.
Acknowledgements
Acknowledgment. This work was supported by the special research fund of Andong National University. The authors would like to thank Dr. Jeen-Woo Park, department of biochemistry, Kyungpook National University and Dr. Chong Ock Lee, medicinal science division, Korea Research Institute of Chemical Technology for biological tests.
References
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