Journal of Natural Products
Article
purified by silica gel chromatography (n-hexane/EtOAc = 2:1).
Violaceoid A (1) (4.1 mg, 67%) was obtained as a white solid.
1 - ( 3 ′ , 6 ′ - B i s ( ( t e r t - b u t y l d i p h e n y l s i l y l ) o x y ) - 2 ′ -
(hydroxymethyl)phenyl)heptan-1-ol (22). To a solution of 14
(200 mg, 0.246 mmol) in MeOH (5.00 mL, 0.05 M) was added p-
toluenesulfonic acid monohydrate (56.0 mg, 0.295 mmol) at 0 °C.
The reaction mixture was stirred for 2 h at rt, diluted with water,
extracted with chloroform, and concentrated. The residue was purified
by silica gel column chromatography (n-hexane/EtOAc = 5:1).
Compound 22 (119 mg, 66%) was obtained as a white solid.
2-(1′-Hydroxyheptyl)-3-(hydroxymethyl)benzene-1,4-diol
(rac-Violaceoid B (2)). To a solution of 22 (77 mg, 0.105 mmol) in
THF/pyridine (5.25 mL, v/v = 1:1, 0.02 M) was added hydrogen
fluoride pyridine complex (2.00 mL) at 0 °C. The reaction mixture
was stirred for 2 h, quenched with saturated aqueous NaHCO3,
extracted with EtOAc, and washed with saturated aqueous copper
sulfate, water, saturated aqueous NaHCO3, and brine. The organic
layer was dried over Na2SO4 and concentrated. The residue was
purified by silica gel chromatography (n-hexane/EtOAc = 2:1). rac-
Violaceoid B (2) (19.2 mg, 72%) was obtained as a white solid.
1 - ( 3 ′ , 6 ′ - B i s ( ( t e r t - b u t y l d i p h e n y l s i l y l ) o x y ) - 2 ′ -
(hydroxymethyl)phenyl)heptyl Acetate (24). To a solution of 14
(32.4 mg, 0.040 mmol) in CH2Cl2 (2.00 mL, 0.02 M) were added
acetic anhydride (7.5 μL, 0.0796 mmol), triethylamine (22.2 μL,
0.159 mmol), and N,N-dimethylpyridin-4-amine (1.0 mg, 0.00796
mmol) at rt. The reaction mixture was stirred for 12 h, quenched with
saturated aqueous NaHCO3, extracted with CH2Cl2 × 2 and EtOAc ×
2, and dried over Na2SO4. The organic layer was filtrated and
concentrated. The residue was purified by silica gel chromatography
(n-hexane/EtOAc = 5:1). The crude product 23 was used for the
following reaction without further purification.
To a solution of the crude product 23 in MeOH/THF (3.35 mL,
v/v = 1:1, 0.01 M) was added p-toluenesulfonic acid monohydrate
(9.6 mg, 0.0503 mmol) at 0 °C. The reaction mixture was stirred for 2
h at rt, quenched with saturated aqueous NaHCO3, extracted with
CH2Cl2 × 2 and EtOAc × 2, and dried over Na2SO4. The organic
layer was filtrated and concentrated. The residue was purified by silica
gel chromatography (n-hexane/EtOAc = 5:1). Compound 24 (20.4
mg, 66% in 2 steps) was obtained as a white solid.
1-(6′-((tert-Butyldiphenylsilyl)oxy)-3′-hydroxy-2′-
(hydroxymethyl)phenyl)heptyl Acetate (13). To a solution of 24
(1.45 g, 1.70 mmol) in THF/pyridine (34.0 mL, v/v = 2:1, 0.050 M)
was added hydrogen fluoride pyridine complex (1.0 mL) at 0 °C. The
reaction mixture was stirred for 2 h, quenched with saturated aqueous
NaHCO3, extracted with EtOAc, and concentrated. Pyridine was
removed by using azetrope with benzene, and the residue was purified
by silica gel chromatography (n-hexane/EtOAc = 3:1). Compound 13
(851 mg, 94%) was obtained as a white solid.
mmol), (R)-benzotetramisole (3.0 mg, 0.0118 mmol), and diphenyl-
acetic anhydride (57.0 mg, 0.141 mmol). The reaction mixture was
stirred for 12 h, quenched with saturated aqueous NaHCO3, extracted
EtOAc, and dried over Na2SO4. The organic layer was filtrated and
concentrated. The residue was purified by silica gel chromatography
(n-hexane/EtOAc = 4:1, then CH2Cl2). Compound (R)-26 (33.1 mg,
29%, 12% ee) was obtained as a colorless oil, and compound (S)-7
(37.1 mg, 54%, 50% ee) was obtained as a white solid.
(S)-5-(1′-Hydroxyheptyl)-2,2-dimethyl-4H-benzo[d][1,3]-
dioxin-6-ol ((S)-7) (95% ee). To a solution of (S)-7 (37.1 mg, 0.126
mmol, 50% ee) in Et2O (1.3 mL, 0.1 M) were added N,N-
diisopropylethylamine (0.014 mL, 0.0339 mmol), (R)-benzotetrami-
sole (1.6 mg, 0.00628 mmol), and diphenylacetic anhydride (13.8 mg,
0.0339 mmol). The reaction mixture was stirred for 12 h, quenched
with saturated aqueous NaHCO3, extracted with EtOAc, and dried
over Na2SO4. The organic layer was filtrated and concentrated. The
residue was purified by silica gel chromatography (n-hexane/EtOAc =
4:1, then CH2Cl2). Compound (S)-7 (35.9 mg, 97%, 54% ee) was
obtained as a white solid. The chiral enriched (S)-7 (18.8 mg, 95%
ee) was obtained by the same kinetic resolution after four repetitions
from the above (S)-7 (35.9 mg, 0.126 mmol, 54% ee).
(S)-7 (95% ee): [α]2D5 −46.3 (c 1.12, CHCl3). Other spectra are the
same as those of rac-7.
(S)-2-(1′-Hydroxyheptyl)-3-(hydroxymethyl)benzene-1,4-
diol ((S)-Violaceoid B, (S)-2)). To a solution of (S)-7 (69.5 mg,
0.236 mmol, 95% ee) in THF/H2O (2.36 mL, v/v = 1:1, 0.1 M) was
added p-toluenesulfonic acid monohydrate (22.4 mg, 0.118 mmol).
The reaction mixture was stirred for 6 h, quenched with saturated
aqueous NaHCO3, extracted with EtOAc, and concentrated. The
residue was purified by silica gel chromatography (n-hexane/EtOAc =
3:1) to afford (S)-violaceoid B (9.2 mg, 15%) as a white solid, and
(S)-7 (59.6 mg, 86%) was recovered.
Additionally, (S)-violaceioid B (25.7 mg) and (S)-7 (27.1 mg)
were obtained by the same reaction after two repetitions from the
recovered (S)-7 (59.6 mg, 0.202 mmol). Therefore, 34.9 mg (total
amount) of (S)-violaceoid (58%) was prepared from the starting 69.5
mg of (S)-7.
(S)-Violaceoid B ((S)-2) (95% ee): [α]2D3 −17.0 (c 0.093, CHCl3),
[α]2D3 −22.5 (c 0.667, MeOH). Other spectra are the same as those of
rac-2.
(S)-1-(6′-Hydroxy-2′,2′-dimethyl-4H-benzo[d][1′,3′]dioxin-
5′-yl)heptyl 2,2-diphenylacetate ((S)-26) and (R)-5-(1′-Hydrox-
yheptyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-ol ((R)-7). To
a solution of rac-7 (123.7 mg, 0.420 mmol) in Et2O (4.2 mL, 0.1 M)
were added N,N-diisopropylethylamine (0.050 mL, 0.303 mmol), (S)-
benzotetramisole (5.0 mg, 0.0210 mmol), and diphenylacetic
anhydride (102 mg, 0.252 mmol). The reaction mixture was stirred
for 12 h, quenched with saturated aqueous NaHCO3, extracted with
EtOAc, and dried over Na2SO4. The organic layer was filtrated and
concentrated. The residue was purified by silica gel chromatography
(n-hexane/EtOAc = 4:1, then CH2Cl2). Compound (S)-26 (65.9 mg,
32%, 19% ee) was obtained as a colorless oil, and compound (R)-7
(60.1 mg, 49%, 58% ee) was obtained as a white solid.
1-(6′-((tert-Butyldiphenylsilyl)oxy)-2′,2′-dimethyl-4H-
benzo[d][1′,3′]dioxin-5′-yl)heptyl Acetate (25). To a solution of
13 (851 mg, 1.59 mmol) in CH2Cl2 (53.1 mL, 0.03 M) were added
2,2-dimethoxypropane (0.49 mL, 3.98 mmol) and p-toluenesulfonic
acid monohydrate (1.5 mg, 0.0796 mmol). The reaction mixture was
stirred for 30 min, quenched with saturated aqueous NaHCO3,
extracted with EtOAc, and concentrated. The residue was purified by
silica gel chromatography (n-hexane/EtOAc = 3:1). Compound 25
(838 mg, 92%) was obtained as a colorless oil.
5-(1′-Hydroxyheptyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-
6-ol (rac-7). To a solution of 25 (422 mg, 0.734 mmol) in THF
(24.5 mL, 0.03 M) was added 1.0 M lithium aluminum hydride in
THF (1.84 mL) at 0 °C. The reaction mixture was stirred for 5 min,
quenched with MeOH and saturated aqueous Rochell’s salt, extracted
with EtOAc, and dried over Na2SO4. The organic layer was filtrated
and concentrated. The residue was purified by silica gel chromatog-
raphy (n-hexane/EtOAc = 3:1). Compound rac-7 (214 mg, 99%) was
obtained as a white solid.
(S)-26 (19% ee): [α]2D6 −0.20 (c 2.39, CHCl3). Other spectra are
the same as those of (R)-26.
(R)-5-(1′-Hydroxyheptyl)-2,2-dimethyl-4H-benzo[d][1,3]-
dioxin-6-ol ((R)-7) (93% ee). To a solution of (R)-7 (60.1 mg,
0.204 mmol, 58% ee) in Et2O (2.0 mL, 0.10 M) were added N,N-
diisopropylethylamine (9.6 μL, 0.0550 mmol), (S)-benzotetramisole
(2.6 mg, 0.0118 mmol), and diphenylacetic anhydride (22.3 mg,
0.0550 mmol). The reaction mixture was stirred for 12 h, quenched
with saturated aqueous NaHCO3, extracted with EtOAc, and dried
over Na2SO4. The organic layer was filtrated and concentrated. The
residue was purified by silica gel chromatography (n-hexane/EtOAc =
4:1, then CH2Cl2). Compound (R)-7 (56.8 mg, 95%, 66% ee) was
obtained as a white solid. The chiral enriched (R)-7 (31.0 mg, 93%
ee) was obtained by the same kinetic resolution after four repetitions
from the above (R)-7 (56.8 mg, 0.193 mmol, 66% ee).
(R)-1-(6′-Hydroxy-2′,2′-dimethyl-4H-benzo[d][1′,3′]dioxin-
5′-yl)heptyl 2,2-Diphenylacetate ((R)-26) and (S)-5-(1′-Hy-
droxyheptyl)-2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-ol ((S)-
7). To a solution of rac-7 (69.3 mg, 0.235 mmol) in Et2O (2.3 mL,
0.1 M) were added N,N-diisopropylethylamine (0.030 mL, 0.169
(R)-7 (93% ee): [α]2D5 +44.6 (c 1.87, CHCl3). Other spectra are the
same as those of rac-7.
F
J. Nat. Prod. XXXX, XXX, XXX−XXX