1
0252
K. A. Parker, Q. Ding / Tetrahedron 56 (2000) 10249±10254
5
4
-methyl 1,3-cyclohexanedione 16 (66 mg, 0.52 mmol) in
mL ethyl alcohol, sodium hydride (2 mg, 0.10 mmol) was
sodium hydroxide (200 mg) in 1 mL water was added and
the resulting mixture was stirred at re¯ux for 6 h. The reac-
tion was quenched with 5% hydrochloric acid and the
mixture was extracted with dichloromethane (3£10 mL).
The combined organic extract was dried (Na SO ) and
added and the mixture was stirred at 08C for 1 h. Ethyl
alcohol was removed and the residue was dissolved in dry
acetone. To the stirred solution, potassium carbonate
2
4
(
1.00 g) and methyl iodide (0.25 mL) were added and the
concentrated to give an orange solid. Chromatography with
50% EtOAc/hexanes gave 28 mg (41%) of Hatomarubigin A.
mixture was stirred at re¯ux for 2.5 h. The mixture was
cooled to room temperature and the solid was removed by
®
solid. Flash chromatography with 50% EtOAc/hexanes
ltration. The ®ltrate was concentrated to yield a yellow
Tri¯uoromethanesulfonate 23. To the stirred solution of
Hatomarubigin A (5) (17 mg, 0.05 mmol) in dichloro-
methane (3 mL), tri¯ic anhydride (17 mg, 0.06 mmol) and
pyridine (0.03 mL) were added successively at 08C. The
mixture was warmed to room temperature and stirred for
100 min before being quenched by the addition of water
(10 mL). The resulting mixture was extracted with dichloro-
methane (3£5 mL) and the combined organic solution was
washed with 5% hydrochloric acid (2£10 mL) and water
(2£10 mL), then dried (Na SO ) and concentrated to yield
gave 67 mg (76%) of a light yellow solid: mp 167±1698C.
IR (CDCl ) 3394, 2962, 2930, 1702, 1675, 1584, 1457,
3
2
400, 1369, 1245, 1186, 1041 cm ; H NMR (CDCl ) d
1 1
1
1
3
3
.22 (d, 3H, J6.4 Hz), 2.30±2.70 (m, 4H), 2.74 (s, 3H),
.15 (dd, 1H, J14, 6 Hz), 4.09 (s, 3H), 6.87 (d, 1H,
J7.4 Hz), 7.40 (t, 1H, J8.0 Hz), 7.78 (d, 1H,
1
3
J8.4 Hz), 9.58 (s, H); C NMR (CDCl ) d 20.9, 30.4,
3
3
1
2
1.9, 32.3, 46.2, 56.3, 105.0, 112.4, 113.5, 116.5, 117.0,
17.6, 122.7, 127.7, 144.1, 148.1, 156.8, 169.7, 192.7,
03.0; MS (m/e) 73 (100), 147 (64.7), 207 (28.7), 221
2
4
22 mg (91%) of a yellow solid. 1R (CDCl ) 2964, 2931,
3
2843, 1706, 1683, 1595, 1473, 1435, 1314, 1262, 1218,
1141, 1028 cm ; H NMR (CDCl ) d 1.21 (d, 3H,
2
1
1
(
19.8), 281 (15.0), 339 (25.2); HRMS calcd for C H O
2
0
18
5
3
3
38.3635, found 338.3629.
J6.3 Hz), 2.40±2.80 (m, 3H), 2.97±3.06 (m, 2H), 4.01
1
s, 3H), 7.28±7.37 (m, 2H), 7.62±7.75 (m, 2H); C NMR
3
(
(CDCl ) d 21.3, 30.7, 38.0, 47.2, 56.6, 117.1, 117.7, 118.9,
O-Methyl ether 21. The above procedure with extended
re¯ux times provided a yellow solid (86%). IR (CDCl )
3
120.3, 121.7, 126.6, 127.1, 135.5, 136.4, 138.5, 148.0,
150.2, 159.7, 179.3, 183.8, 197.4; HRMS calcd for
C H F SO 468.4087, found 468.4068.
3
2
705, 1678, 1630, 1576, 1519, 1460 cm . H NMR
1
1
1
(
2
(
CDCl ) d 1.23 (d, 3H, J6.3 Hz), 2.30±2.88 (m, 4H),
3
21 15
3
7
.74 (s, 3H), 3.10 (dd, 1H, J14, 6 Hz), 3.83 (s, 3H), 4.05
s, 3H), 6.97 (dd, 1H, J0.6, 8.2 Hz), 7.51 (t, 1H,
Rubiginone B (3). Tri¯ate 23 (15 mg, 0.03 mmol), palla-
2
1
3
J8.0 Hz), 7.83 (d, 1H, J8.2 Hz); C NMR (CDCl ) d
dium (II) acetate (2.3 mg, 0.002 mmol), triphenylphosphine
(2.1 mg, 0.008 mmol), triethylamine (11 mg, 0.11 mmol)
and formic acid (80%, 2.7 mL) were combined and the
mixture was stirred at 508C for 3 h and then diluted with
dichloromethane (15 mL). The combined organic solution
washed with 5% hydrochloric acid (2£10 mL) and with
water (20 mL). Then it was dried (Na SO ) and concen-
3
2
1
1
1.0, 30.5, 31.9, 32.9, 46.2, 56.0, 64.4, 106.2, 112.7, 115.2,
17.0, 117.1, 123.5, 127.8, 128.0, 147.2, 149.5, 156.6,
69.9, 192.9, 203.0; HRMS calcd for C H O 352.3906,
2
1
20
5
found 352.3900.
Hatomarubigin A (2) from naphthofuran 13. To the
stirred solution of naphthofuran 13 (20 mg, 0.06 mmol) in
3
ide solution (prepared by dissolving 0.60 g of sodium
hydroxide in a mixture of 1 mL of water and 5 mL ethyl
alcohol). The mixture was purged with N , stirred at re¯ux
for 5.5 h, and then cooled. The reaction was quenched with
10% hydrochloric acid and the resulting mixture was
2
4
trated. The residual yellow solid was chromatographed
with 50% EtOAc/hexanes to give 10 mg (98%) of a yellow
solid, mp 2358C-dec. IR (CDCl ) 1700, 1672, 1594 cm ;
mL of ethyl alcohol was added 2.5 mL of sodium hydrox-
2
1
3
1
H NMR (CDCl ) d 1.19 (d, 3H, J6.4 Hz), 2.40±2.60 (m,
3
2H), 2.61±2.75 (m, 2H), 2.90±3.10 (m, 1H), 4.04 (s, 3H),
7.28 (d, 1H, J8.0 Hz), 7.49 (d, 1H, J8.0 Hz), 7.68 (t, 1H,
J8.0 Hz), 7.76 (d, 1H, J8.0 Hz), 8.25 (d, 1H, J8.0 Hz);
2
1
3
extracted with ether (3£7 mL). The combined extract was
C NMR (CDCl ) d 21.4, 30.8, 38.3, 50.2, 56.5, 108.2,
3
dried (Na SO ) and concentrated. Flash chromatography
2
117.2, 119.7, 120.7, 129.6, 133.0, 135.0, 135.1, 135.3,
137.7, 149.1, 159.8, 181.6, 184.5, 198.8; MS (m/e) 63
(15.6), 82 (15.2), 151 (24.6), 163 (53.9), 176 (16.8), 189
(14.6), 221 (16.4), 249 (42.1), 261 (30.9), 278 (100), 293
(32), 305 (17.3), 320 (98.4); HRMS calcd for C H O
4
4
(
5% ether in CH C1 ) of the solid orange residue gave
2 2
10 mg (51%) of a pale orange solid, mp 237±2388C. IR
2
1 1
(
KBr) 3349, 1696, 1676, 1639 cm ; H NMR (CDCl ) d
3
1
.16 (d, 3H, J6.3 Hz), 2.30±2.70 (m, 3H), 2.80±3.0
2
0
16
(
m, 2H), 4.04 (s, 3H), 6.95 (s, 1H), 7.25±7.33 (m, 1H),
320.1048, found 320.1042.
1
.69±7.76 (m, 2H), 13.05 (s, 1H); C NMR (CDCl ) d
3
7
2
1
1
3
1.3, 30.2, 38.6, 47.5, 56.6, 117.4, 117.7, 119.7, 119.9,
20.9, 128.1, 136.3, 137.4, 137.7, 158.2, 160.3, 163.6,
84.5, 188.4, 197.8; MS (m/e) 63 (7.6), 139 (21.3), 152
X-14881 E (6). Rubiginone B2 (3, 10 mg, 0.031 mmol),
palladium (II) chloride (11 mg, 0.06 mmol), concentrated
hydrochloric acid (2 mL) and t-butyl alcohol (2 mL) were
combined and the mixture was stirred at re¯ux until TLC
showed no starting material (40 min). The mixture was
cooled and the reaction was quenched with 5% hydrochloric
acid (10 mL). The resulting mixture was extracted with
dichloromethane (3£5 mL) and the extract was dried
(Na SO ) and concentrated to yield a dark red solid.
(
(
21.1), 220 (16.3), 248 (11.9), 264 (9.3), 276 (9.3), 294
100), 308 (39.8), 336 (58.7); HRMS calcd for C H O
5
2
0
16
336.0998, found 336.1000.
Hatomarubigin A (2) from naphthoquinone 15 and dike-
tone 16. To a stirred suspension of naphthofuran 15 (40 mg,
2
4
0.2 mmol) and diketone 16 (30 mg, 0.24 mmol) in 4 mL of
ethyl alcohol, sodium hydride (3 mg. 0.12 mmol) was added
and the mixture was stirred at 08C for 1 h. Then a solution of
Chromatography with 33% EtOAc/hexanes yielded 9.8 mg
(98%) of a dark orange solid. IR (CDCl ) 1662, 1620,
1586 cm ; H NMR (CDCl ) d 2.49 (s, 3H), 4.08 (s, 3H),
3
3
2
1 1