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.
Konishi M.
,
Ohkuma H.
,
Matsumoto K.
,
Tsuno T.
,
Kamei H.
,
Miyaki T.
,
Oki T.
,
Kawaguchi H.
,
VanDuyne G. D.
,
Clardy J.
1989
J. Antibot.
42
1449 -
DOI : 10.7164/antibiotics.42.1449
Kim J.H.
,
Ryoo K. S.
,
Choi. J.-H.
,
Hong Y. P.
2000
Bull. Korean Chem. Soc.
21
37 -
Nicolaou K. C.
,
Dai W.-M.
,
Hong Y. P.
,
Tsay S.-C.
,
Baldridge K. K.
,
Siegel J. S.
1993
J. Am. Chem. Soc.
115
7944 -
DOI : 10.1021/ja00071a003