40
S. Yamaguchi, M. Nedachi, M. Maekawa, Y. Murayama, M. Miyazawa, and Y. Hirai
Vol. 43
MHz): δ 1.62 (s, 3H), 2.67 (s, 3H), 2.75 (s, 2H), 3.66 (s, 3H), 3.85
(s, 3H), 6.32 (s, 1H), 7.52 (s, 1H), 9.46 ppm (s, 1H).
Patterson Conversion of 25 to Mycochromenic Acid 2.
Under an argon atmosphere, a solution of tetramethylethyl-
enediamine (88.5 µL, 0.589 mmol) and 1.0 M sec-butyl lithium
cyclohexane solution (78.9 µL, 0.586 mmol) in dry THF (1.67
mL) was cooled to –90 °C. A solution of 25 (100 mg, 0.266
mmol) in dry tetrahydrofuran (1.13 mL) was added cautiously to
the cooled sec-butyl lithium solution, and the mixture was
stirred for 1 hr at the same temperature. A solution of N,N-
dimethylformamide (46.8 mg, 0.586 mmol) in dry tetrahydrofu-
ran (0.6 mL) was added to the mixture, which was allowed to
warm to –30 °C and stirred for 1 hr at that temperature. After
quenching with ice-water, the mixture was extracted with ethyl
acetate. The organic layer was washed with brine, and then
dried over anhydrous sodium sulfate. After removal of the sol-
vent in vacuo, the residue was purified by chromatography on a
silica gel column to afford the crude 7-carbaldehyde (22 mg).
To a solution of this aldehyde in ethanol (0.1 mL) was added
sodium borohydride (2.00 mg, 5.03 µmol), and the mixture was
stirred at room temperature for 24 hrs. After quenching the
excess amount of sodium borohydride with acetic acid for 1 hr,
the mixture was poured onto saturated aqueous sodium hydro-
gen carbonate solution and extracted with ethyl acetate. The
organic layer was washed with brine, and dried over anhydrous
sodium sulfate. After removal of the solvent in vacuo the
residue was purified on a silica gel column to afford the methyl
ester 34 (14 mg); a colorless oil eluted with hexane-ethyl acetate
Methyl 8-Formyl-5-methoxy-2,6-dimethyl-2H-chromene-2-
propanoate (29a).
This compound was obtained as a pale yellow oil eluted with
hexane-ethyl acetate (8:2); 68% yield; ir (liquid film): ν 1738,
-1 1
1681 cm ; H nmr (CDCl , 400 MHz): δ 1.46 (s, 3H), 1.90-2.20
3
(m, 2H), 2.21 (s, 3H), 2.30-2.50 (m, 2H), 3.65 (s, 3H), 3.78 (s,
3H), 5.63 (d, J = 10 Hz, 1H), 6.67 (d, J = 10 Hz, 1H), 7.50 (s,
+
+
1H), 10.35 ppm (s, 1H); ms (EI): m/z 304 (M ), 289 (M -CH ),
3
+
217 (M -CH CH CN). Hrms. Calcd for C
H O : M 304.131.
2
2
17 20 5
+
Found: M 304.126.
Oxidation of 29a with Sodium Chlorite.
To a solution of aldehyde 29a (136 mg, 0.500 mmol) in
dimethylsulfoxide (7 mL) was added a solution of sodium dihy-
drogen phosphate (30 mg, 0.19 mmol) in water (1,5 mL). Under
ice cooling, sodium chlorite (127 mg, 1.41 mmol) in water (1.5
mL) was added, and the solution was stirred at room temperature
for 17 hrs. The mixture was alkalified with a sodium hydrogen
carbonate solution and washed with dichloromethane. The alka-
line aqueous layer was collected, acidified with 10% hydrochlo-
ric acid, and extracted with dichloromethane. The organic layer
was washed with brine, and dried over anhydrous sodium sulfate.
After removal of the solvent in vacuo the residue was purified by
chromatography on a silica gel column to afford corresponding
acid 5-methoxy-2-(2-methoxycarbonyl)ethyl-2,6-dimethyl-2H-
chromene-8-carboxylic acid (29b); a pale yellow oil eluted with
hexane-ethyl acetate (7:3); 97%; ir (liquid film): ν 2608-3296,
-1
1
(95:5); ir (liquid film): ν 1766, 1739 cm ; H nmr (CDCl , 400
3
MHz): δ 1.50 (s, 3H), 1.90-2.20 (m, 2H), 2.11 (s, 3H), 2.30-2.70
(m, 2H), 3.65 (s, 3H), 3.78 (s, 3H), 5.09 (s, 2H), 5.62 (d, J = 10
+
Hz, 1H), 6.63 ppm (d, J = 10 Hz, 1H); ms (EI): m/z 332 (M ),
-1 1
1737 cm ; H nmr (CDCl , 400 MHz): δ 1.53 (s, 3H), 2.20-2.30
3
+
245 (M -CH CH CO CH ).
2
2
2
3
(m, 2H), 2.24 (s, 3H), 2.30-2.60 (m, 2H), 3.66 (s, 3H), 3.79 (s,
To a solution of methyl ester 34 (14 mg) in methanol (5 mL)
and water (5 mL) was added lithium hydroxide monohydrate
(3.90 mg, 92.7 µmol), and the mixture was stirred at room tem-
perature for 2 hrs. The resulting mixture was diluted with a satu-
rated sodium hydrogen carbonate solution and washed with ethyl
ether. The alkaline aqueous layer was collected, acidified with
10% hydrochloric acid, and extracted with ethyl acetate. The
ethyl acetate layer was dried over anhydrous sodium sulfate.
After removal of the solvent in vacuo the residue afforded pure
mycochromenic acid 2 (12 mg) without further purification.
Mycochromenic Acid 2 was obtained as colorless crystals;
3H), 5.67 (d, J = 10 Hz, 1H), 6.72 (d, J = 10 Hz, 1H), 7.83 ppm
+
+
+
(s, 1H); ms (EI): m/z 320 (M ), 305 (M -CH ), 233 (M -
3
CH CH CO CH ).
2
2
2
3
Anal. Calcd. for C
H O : C, 63.74; H, 6.29. Found: C,
17 20 6
63.51; H, 6.33.
Carboxamidation of 29b to 29d.
To a solution of carboxylic acid 29b (0.300 mmol) in dry ben-
zene (5 mL) was added a solution of thionyl chloride (0.043 mL,
0.60 mmol) in dry benzene (5 mL), and the mixture was refluxed
for 1 hr. After removal of the benzene and the excess thionyl
chloride, the residual crude acid chloride 29c was diluted with
dry benzene (5 mL) and stirred with a solution of diethylamine
(66 mg, 0.90 mmol) in dry benzene (10 mL) at room temperature
for 1 hr. The mixture was treated with sodium hydrogen carbon-
ate solution, and extracted with ethyl acetate. The organic layer
was washed with brine, and dried over anhydrous sodium sulfate.
After removal of the solvent in vacuo, the residue was purified by
chromatography on a silica gel column to afford N,N-diethyl-5-
methoxy-2-(2-methoxycarbonyl)ethyl-2,6-dimethyl-2H-
chromene-8-carboxamide (25); a pale yellow oil eluted with
hexane-ethyl acetate (7:3); 87%; ir (liquid film): ν 1739, 1633
-
14% (from 25); mp 162-163 °C; ir (KBr disk): ν 1744, 1717 cm
1 1
; H nmr (CDCl , 400 MHz): δ 1.52 (s, 3H), 2.05-2.17 (m, 2H),
3
2.11 (s, 3H), 2.50-2.70 (m, 2H), 3.78 (s, 3H), 5.10 (s, 2H), 5.62
(d, J = 10 Hz, 1H), 6.64 ppm (d, J = 10 Hz, 1H); C nmr (CDCl ,
13
3
400 MHz): δ 10.9, 26.3, 29.7, 35.9, 61.7, 68.4, 79.2, 108.4, 114.7,
116.3, 117.8, 128.9, 147.8 159.5, 168.9 ppm; ms (EI): m/z 318
+
+
(M ), 245 (M -CH CH CO H).
2
2
2
Side-Chain Conversion of 32c to Mycochromenic Acid 2.
Deprotection.
To a solution of pyranophthalide 32c (53 mg, 0.15 mmol) in
methanol (3 mL), was added a catalytic amount of concentrated
hydrochloric acid, and the mixture was refluxed for 3 hrs. After
cooling, the mixture was concentrated in vacuo, and the residue
was diluted with ethyl acetate. The ethyl acetate layer was
washed with a saturated sodium hydrogen carbonate solution and
brine, and dried over anhydrous sodium sulfate. After removal of
the solvent in vacuo, the residue was purified by chromatography
-1
1
cm ; H nmr (CDCl , 400 MHz): δ 1.05 (t, J = 7 Hz, 3H), 1.23
3
(t, J = 7 Hz, 3H), 1.36 (s, 3H), 2.04 (m, 2H), 2.18 (s, 3H), 2.43
(m, 2H), 3.21 (m, 2H), 3.64 (s, 3H), 3.72 (s, 3H), 5.58 (d, J = 10
Hz, 1H), 6.65 (d, J = 10 Hz, 1H), 6.86 ppm (s, 1H); ms (EI): m/z
+
+
+
375 (M ), 360 (M -CH ), 287 (M -CH CH CO CH ).
3
2
2
2
3
Anal. Calcd. for C
H NO : C, 67.18; H, 7.79; N, 3.73.
16 29 5
Found: C, 66.94; H, 7.55; N, 3.57.
Yamaguchi, Seiji
