Dehydroherbarin and 6-Deoxybostrycoidin
J . Org. Chem., Vol. 65, No. 3, 2000 643
Syn th esis of 3-Aceton yl-8-h yd r oxy-6-m eth oxy-2-m eth -
yl-1,4-n a p h th oqu in on e (15) a n d 1-Acetyl-6-h yd r oxy-8-
m eth oxy-2-m eth yl-5,10-a n th r a qu in on e (16). Under a ni-
trogen atmosphere, a solution of triethylamine (0.25 g, 2.5
mmol) in acetonitrile (5 mL) was added dropwise to a stirred
solution of 8-hydroxy-6-methoxy-2-methyl-1,4-naphthoquinone
(13) (0.55 g, 2.5 mmol) and acetonylpyridinium chloride (14)10
(0.45 g, 2.6 mmol) in acetonitrile (30 mL). Stirring was
continued for 16 h, and then most of the solvent was evapo-
rated in vacuo. The residue was dissolved in 2 N hydrochloric
acid and extracted with ethyl acetate. The combined extracts
were washed with water and brine, dried (MgSO4), and
evaporated in vacuo to give a mixture of 3-acetonyl-8-hydroxy-
6-methoxy-2-methyl-1,4-naphthoquinone (15) and 1-acetyl-6-
methyl-1,4-naphthoquinone (21) (4.38 g, 63%) as a yellow
powder. For the spectral data of compound 21, vide supra.
3-Acet on yl-6,8-d im et h oxy-2-m et h yl-1,4-n a p h t h oq u i-
n on e (22). To a solution of 6,8-dimethoxy-2-methyl-1,4-
naphthoquinone (21) (0.35 g, 1.5 mmol) and acetonylpyridin-
ium chloride (14)10 (0.26 g, 1.5 mmol) in acetonitrile (20 mL)
was added dropwise a solution of triethylamine (0.15 g, 1.5
mmol) in acetonitrile (5 mL), and the resulting solution was
stirred for 16 h at room temperature under
a nitrogen
atmosphere and protected from light with aluminum foil. Most
of the solvent was evaporated in vacuo, and the residue was
mixed with 2 N hydrochloric acid and extracted with ethyl
acetate. The combined organic phases were washed with a
saturated solution of sodium hydrogen carbonate, dried (Mg-
SO4), and evaporated in vacuo. Recrystallization from ethyl
acetate afforded 3-acetonyl-6,8-dimethoxy-2-methyl-1,4-naph-
thoquinone (22) (0.34 g, 79%) as a yellow powder, mp 181.7-
hydroxy-8-methoxy-2-methyl-5,10-anthraquinone (16) in
a
ratio of 3:1 which could not be separated by flash chromatog-
raphy using ethyl acetate-petroleum ether (1:1) as eluent.
Selective recrystallization from ethyl acetate afforded 1-acetyl-
6-hydroxy-8-methoxy-2-methyl-5,10-anthraquinone (16) (110
mg, 15%) as a yellow powder, mp 217.5-218 °C. 1H NMR
(CDCl3): δ 2.40 (3H, s, CH3), 2.58 (3H, s, CH3CdO), 3.92 (3H,
s, MeO), 6.72 (1H, d, J ) 2.3 Hz, H-7), 7.30 (1H, d, J ) 2.3
Hz, H-9), 7.65 (1H, d, J ) 7.9 Hz, H-3), 8.24 (1H, d, J ) 7.9
Hz, H-4). 13C NMR (CDCl3): δ 19.12 (CH3), 31.02 (CH3CdO),
56.06 (MeO), 107.13 (C-9), 107.99 (C-7), 110.37 (dCquat), 127.20
(C-4), 130.01 (dCquat), 131.88 (dCquat), 134.55 (dCquat), 136.57
(C-3), 140.32 (dCquat), 143.56 (dCquat), 165.33 (dC-O), 166.45
(dC-O), 182.85 (CdO), 186.02 (CdO), 205.19 (CdO). IR
(KBr): νmax 3465 (OH), 1694 (CdO), 1669 (CdO), 1622 (CdO)
cm-1. MS m/z (%): 310 (M+, 62), 296 (41), 294 (100). Anal.
Calcd for C18H14O5: C, 69.67; H, 4.55. Found: C, 68.65; H,
4.85. Evaporation of the mother liquor and recrystallization
from ethanol gave pure 3-acetonyl-8-hydroxy-6-methoxy-2-
methyl-1,4-naphthoquinone (15) (200 mg, 29%) as a yellow
1
182.9 °C. H NMR (CDCl3): δ 2.09 (3H, s, CH3), 2.30 (3H, s,
CH3CdO), 3.74 (2H, s, CH2), 3.92 (3H, s, MeO), 3.96 (3H, s,
MeO), 6.71 (1H, d, J ) 2.3 Hz, H-7), 7.21 (1H, d, J ) 2.3 Hz,
H-5). 13C NMR (CDCl3): δ 13.53 (CH3), 30.13 (CH3CdO), 41.62
(CH2), 55.88 (MeO), 56.42 (MeO), 103.09 (C-5), 104.10 (C-7),
114.68 (dCquat), 135.69 (dCquat), 137.72 (dCquat), 147.94 (dCquat),
161.74 (dC-O), 164.42 (dC-O), 182.76 (CdO), 184.35 (Cd
O), 203.66 (CdO). IR (KBr): νmax 1707 (CdO), 1646 (CdO),
1596 (CdC) cm-1. MS m/z (%): 288 (M+, 18), 246 (30), 209
(41), 45 (100). Anal. Calcd for C16H16O5: C, 66.66; H, 5.59.
Found: C, 66.24; H, 5.54.
3-Acet on yl-2-b r om om et h yl-6,8-d im et h oxy-1,4-n a p h -
th oqu in on e (23). A mixture of 3-acetonyl-6,8-dimethoxy-2-
methyl-1,4-naphthoquinone (22) (0.86 g, 3 mmol), N-bromo-
succinimide (0.56 g, 3.15 mmol), and benzoyl peroxide (0.07
g, 0.3 mmol) in carbon tetrachloride (80 mL) was heated under
reflux for 6 h, cooled to room temperature, and evaporated in
vacuo. Recrystallization from ethyl acetate gave 3-acetonyl-
2-bromomethyl-6,8-dimethoxy-1,4-naphthoquinone (23) (0.88
g, 80%) as a yellow powder, mp 140 °C (dec). 1H NMR
(CDCl3): δ 2.36 (3H, s, CH3), 3.83 (2H, s, CH2CdO), 3.94 (3H,
s, MeO), 3.98 (3H, s, MeO), 4.38 (2H, s, CH2Br), 6.74 (1H, d,
J ) 2.3 Hz, H-7), 7.23 (1H, d, J ) 2.3 Hz, H-5). 13C NMR
(CDCl3): δ 22.46 (CH2Br), 30.48 (CH3), 41.44 (CH2CdO), 55.99
(MeO), 56.51 (MeO), 103.47 (C-5), 104.47 (C-7), 114.21 (dCquat),
135.61 (dCquat), 139.85 (dCquat), 145.42 (dCquat), 162.21 (dC-
O), 164.87 (dC-O), 179.67 (CdO), 184.56 (CdO), 202.78
(CdO). IR (KBr): νmax 1706 (CdO), 1651 (CdO), 1595 (CdC)
cm-1. MS m/z (%): 366/8 (M+, 1), 287 (3), 245 (14), 75 (100).
Anal. Calcd for C16H15BrO5: C, 52.34; H, 4.12. Found: C, 52.80;
H, 3.98.
Deh yd r oh er ba r in (7). A solution of triethylamine (0.10
g, 1 mmol) in toluene (5 mL) was added dropwise to a stirred
solution of 3-acetonyl-2-bromomethyl-6,8-dimethoxy-1,4-naph-
thoquinone (23) (0.36 g, 1 mmol) in toluene (30 mL), and the
mixture was heated under reflux for 3 h. The solvent was
evaporated in vacuo, and the residue was chromatographed
on silica gel with ethyl acetate-petroleum ether (1:1) as eluent
to give dehydroherbarin (7) (240 mg, 84%) as a red powder.
Recrystallization from ethanol afforded dehydroherbarin as
fine red needles, mp 187.2-187.5 °C (lit.7 mp 186-188 °C).
The spectral data (1H NMR, IR, and MS) of the synthetic
dehydroherbarin (7) were identical with those of the natural
product reported in the literature.7 Additionally, its 13C NMR
spectral data are given here. 1H NMR (CDCl3): δ 1.99 (3H, d,
J ) 1 Hz, CH3), 3.93 (3H, s, MeO), 3.94 (3H, s, MeO), 5.11
(2H, s, CH2), 5.82 (1H, m, H-4), 6.69 (1H, d, J ) 2.3 Hz, H-8),
7.22 (1H, d, J ) 2.3 Hz, H-6). 13C NMR (CDCl3): δ 20.09 (CH3),
55.88 (MeO), 56.37 (MeO), 63.32 (CH2), 93.78 (C-4), 103.48
(C-6), 104.26 (C-8), 114.57 (dCquat), 124.76 (dCquat), 135.33
(dCquat), 135.58 (dCquat), 161.49 (dC-O), 163.20 (dC-O),
164.11 (dC-O), 180.86 (CdO), 182.23 (CdO). IR (KBr): νmax
1652 (CdO), 1622 (CdO), 1586 (CdC), 1552 (CdC) cm-1. MS
m/z (%): 286 (M+, 96), 271 (100), 243 (18). Anal. Calcd for
1
powder, mp 124.5-124.8 °C. H NMR (CDCl3): δ 2.10 (3H, s,
CH3), 2.31 (3H, s, CH3CdO), 3.77 (2H, s, CH2), 3.89 (3H, s,
MeO), 6.62 (1H, d, J ) 2.6 Hz, H-7), 7.14 (1H, d, J ) 2.6 Hz,
H-5), 12.33 (1H, s, OH). 13C NMR (CDCl3): δ 12.72 (CH3), 30.26
(CH3CdO), 41.69 (CH2), 55.97 (MeO), 106.05 (C-7), 107.74 (C-
5), 109.65 (dCquat), 133.30 (dCquat), 140.91 (dCquat), 146.263
(dCquat), 164.24 (dC-O), 165.86 (dC-O), 183.36 (CdO),
188.03 (CdO), 203.20 (CdO). IR (KBr): νmax 1709 (CdO), 1658
(CdO), 1633 (CdO), 1609 (CdC) cm-1. MS m/z (%): 274 (M+,
30), 232 (100), 204 (11), 43 (77). Anal. Calcd for C15H14O5: C,
65.69; H, 5.14. Found: C, 65.59; H, 4.96.
Syn t h esis of 6,8-Dim et h oxy-2-m et h yl-1,4-n a p h t h o-
qu in on e (21) fr om 8-Hyd r oxy-6-m eth oxy-2-m eth yl-1,4-
n a p h th oqu in on e (13). A mixture of 8-hydroxy-6-methoxy-
2-methyl-1,4-naphthoquinone (13) (0.65 g, 3 mmol), silver(I)
oxide (3.48 g, 15 mmol), and iodomethane (2.59 g, 18 mmol)
in chloroform (30 mL) was protected from light with aluminum
foil and stirred for 10 days under a nitrogen atmosphere. The
reaction mixture was filtered over Celite and evaporated in
vacuo. Recrystallization of the residue from methanol gave 6,8-
dimethoxy-2-methyl-1,4-naphthoquinone (21) (0.66 g, 95%) as
a yellow powder, mp 153.8-155.6 °C. 1H NMR (CDCl3): δ 2.15
(3H, d, J ) 1.3 Hz, CH3), 3.94 (3H, s, MeO), 3.97 (3H, s, MeO),
6.72-6.74 (2H, m, H-3 and H-7), 7.22 (1H, d, J ) 2.3 Hz, H-5).
13C NMR (CDCl3): δ 16.86 (CH3), 55.87 (MeO), 56.30 (MeO),
102.69 (C-5), 103.89 (C-7), 114.48 (dCquat), 132.94 (C-3), 136.21
(Cquat), 150.35 (dCquat), 161.83 (dC-O), 164.45 (dC-O), 183.39
(CdO), 184.87 (CdO). IR (KBr): νmax 1652 (CdO), 1625 (CdO),
1593 (CdC) cm-1. MS m/z (%): 232 (M+, 100), 217 (10), 203
(41). Anal. Calcd for C13H12O4: C, 67.23; H, 5.21. Found: C,
66.98; H, 5.42.
Syn t h esis of 6,8-Dim et h oxy-2-m et h yl-1,4-n a p h t h o-
qu in on e (21) fr om 2-Br om o-6-m eth yl-1,4-ben zoqu in on e
(11). To a solution of 2-bromo-6-methyl-1,4-benzoquinone (11)
(6.03 g, 0.03 mol) in dimethyl sulfoxide (30 mL) was added at
0 °C dimethyl ketene acetal (13.2 g, 0.15 mol), and the solution
was stirred for 4 days under a nitrogen atmosphere. The
reaction mixture was poured into water and extracted three
times with ether, and the combined organic phases were
washed with brine, dried (MgSO4), and evaporated in vacuo.
Recrystallization from ethanol afforded the 6,8-dimethoxy-2-
C
16H14O5: C, 67.13; H, 4.93. Found: C, 67.08; H, 5.23.
Rea ction of 3-Aceton yl-2-br om om eth yl-6,8-d im eth oxy-
1,4-n a p h t h oq u in on e (23) w it h Am m on ia . To a solution