Zou et al.
combined ether extracts were washed with water and brine,
dried (MgSO4), and concentrated to yield 180 mg (94%) of crude
product. Flash chromatography on MeOH-deactivated silica
gel (6:1 hexanes/EtOAc) yielded 44 mg (23%) of pure 21c and
47 mg (26%) of pure 21t.
Purification of 18 mg of the 1.6:1 mixture of 19 and 22 by
preparative TLC (Silica gel 60 F254, 1:1 hexanes/EtOAc,
extracted with MeOH) provided 11.0 mg of 19 and 6.1 mg of
22. Purification of 23 mg of the 1:1:1.5 mixture of 21t, 20c,
and 20t by preparative TLC (Silica gel 60 F254, 1:1 hexanes/
EtOAc, extracted with MeOH) provided 5.5 mg of 21t, 5.6 mg
of 20c, and 8.1 mg of 20t. Purification of 17 mg of the 2:1
acid to pH 5-6 and extracted with ether. The combined ether
extracts were washed with water and brine, dried (MgSO4),
and concentrated to yield 180 mg (94%) of crude product. Flash
chromatography on MeOH-deactivated silica gel (6:1 hexanes/
EtOAc) yielded 76 mg (40%) of pure 13c and 86 mg (45%) of
pure 13t.
Data for 13c: 1H NMR (CDCl3) 12.96 (s, 1, OH), 7.70 (d, 1,
J ) 8.5), 6.49 (d, 1, J ) 8.5), 5.63 (dd, 1, J ) 6.4, 4.2), 5.17 (t,
1, J ) 7.0), 4.37 (d, 1, J ) 6.4), 3.38 (s, 1, OH), 3.32 (d, 1, J )
4.2, OH), 2.56 (s, 3), 2.25-2.13 (m, 2), 1.99-1.91 (m, 1), 1.86-
1.78 (m, 1), 1.71 (s, 3), 1.65 (s, 3), 1.46 (s, 3); 13C NMR (CDCl3)
202.9, 166.6, 160.9, 134.8, 132.2, 123.9, 116.2, 114.8, 102.9,
90.7, 74.3, 70.2, 38.9, 26.4, 25.7, 24.0, 22.1, 17.7; IR (neat) 3357,
2928, 1640, 1370, 1263; HRMS (FAB) calcd for C18H24O5Na
(MNa+) 343.1521, found 343.1518.
mixture of 21t and 23 by preparative TLC (Silica gel 60 F254
,
1:1 hexanes/EtOAc, extracted with MeOH) provided 10.4 mg
of 21t and 5.1 mg of 23.
Data for 20c: 1H NMR (CD3OD) 9.98 (s, 1), 7.60 (d, 1, J )
8.5), 6.47 (d, 1, J ) 8.5), 5.46 (d, 1, J ) 6.1), 5.19 (t, 1, J )
7.0), 4.36 (d, 1, J ) 6.1), 2.23-2.17 (m, 2), 1.91-1.84 (m, 2),
1.70 (s, 3), 1.66 (s, 3), 1.46 (s, 3); 13C NMR (CD3OD) 189.0,
166.1, 163.3, 132.7, 130.3, 125.7, 117.9, 114.8, 111.0, 93.0, 75.5,
70.3, 39.8, 26.0, 23.7, 23.2, 17.9; Rf (1:1 hexanes/EtOAc) 0.50;
HRMS (DCI/NH3) calcd for C17H24NO4 (M + NH3 - OH)+
306.1705, found 306.1694.
Data for 13t: mp 147-148 °C; 1H NMR (CDCl3) 12.94 (s, 1,
OH), 7.68 (d, 1, J ) 8.8), 6.43 (d, 1, J ) 8.8), 5.63 (d, 1, J )
3.9), 5.14 (t, 1, J ) 7.0), 4.51 (d, 1, J ) 3.9), 2.70 (s, 1, OH),
2.56 (s, 3), 2.17 (dt, 2, J ) 7.0, 7.0), 1.81 (s, 1, OH), 1.69 (s, 3),
1.67-1.58 (m, 2), 1.64 (s, 3), 1.28 (s, 3); 13C NMR (CDCl3) 202.9,
166.8, 161.3, 134.7, 132.5, 123.9, 115.5, 114.7, 102.5, 97.4, 73.3,
70.6, 37.1, 26.4, 25.7, 22.4, 21.8, 17.7; IR (KBr) 3310, 2940,
1647, 1257; HRMS (FAB) calcd for C18H24O5Na (MNa+)
343.1521, found 343.1535.
1
Data for 20t: mp 125-127 °C; H NMR (CD3OD) 9.95 (s,
1), 7.57 (d, 1, J ) 8.5), 6.43 (d, 1, J ) 8.5), 5.43 (d, 1, J ) 3.9),
5.13 (t, 1, J ) 7.0), 4.47 (d, 1, J ) 3.9), 2.15 (dt, 2, J ) 7.0,
7.0), 1.68 (s, 3), 1.63 (s, 3), 1.61-1.52 (m, 2), 1.21 (s, 3); 13C
NMR (CD3OD) 188.8, 166.7, 164.2, 132.6, 132.5, 125.5, 117.0,
114.1, 111.0, 99.8, 73.0, 71.0, 38.8, 25.9, 22.9, 22.0, 17.7; IR
(KBr) 3333, 2930, 1670, 1600, 1260; Rf (1:1 hexanes/EtOAc)
0.40; HRMS (DCI/NH3) calcd for C17H24NO4 (M + NH3 - OH)+
306.1705, found 306.1700.
(2S,3R)-1-[2,3-cis-3,4-Dihydroxy-2-(1-hydroxy-1-meth-
ylethyl)-2,3-dihydrobenzofuran-5-yl]-3-(4-hydroxyphenyl)-
E-propenone (6c) and Brosimacutin G (6t). A solution of
(S)-3,3-dimethyloxirane-2-carboxaldehyde ((S)-26))27 (20 mg,
0.20 mmol), isoliquiritigenin (25)26 (52 mg, 0.20 mmol), CaCl2
(24 mg, 0.22 mmol), and KOH (25 mg, 0.44 mmol) in MeOH
(2 mL) was stirred at 25 °C for 1 d. The reaction was
neutralized with 10% citric acid to pH 5-6 and extracted with
ether. The combined ether extracts were washed with water
and brine, dried (MgSO4), and concentrated to yield 63 mg
(90%) of crude product. Flash chromatography on silica gel
(20:1 CH2Cl2/MeOH) yielded 31 mg (43%) of pure 6c and 35
mg (47%) of pure 6t.
Data for 21c: 1H NMR (CDCl3) 11.63 (s, 1, OH), 9.65 (s, 1),
7.42 (d, 1, J ) 8.5), 6.55 (d, 1, J ) 8.5), 5.59 (d, 1, J ) 6.1),
5.16 (t, 1, J ) 6.9), 4.34 (d, 1, J ) 6.1), 4.12 (br s, 1, OH), 3.77
(br s, 1, OH), 2.23-2.11 (m, 2), 1.97-1.89 (m, 1), 1.84-1.78
(m, 1), 1.70 (s, 3), 1.64 (s, 3), 1.45 (s, 3); 13C NMR (CDCl3) 194.5,
167.4, 160.0, 137.9, 132.2, 123.8, 116.2, 116.1, 104.0, 90.8, 74.5,
69.8, 38.8, 25.7, 24.0, 22.1, 17.7; IR (neat) 3356, 2928, 1648,
1254, 1082; Rf (1:1 hexanes/EtOAc) 0.75; HRMS (DCI/NH3)
calcd for C17H23O5 (MH+) 307.1545, found 307.1530.
Data for 6c: mp 207-208 °C; [R]20D +111.2 (c 0.5, MeOH);
1H NMR (CD3OD) 8.12 (d, 1, J ) 8.9), 7.82 (d, 1, J ) 15.2),
7.64 (d, 2, J ) 8.6), 7.63 (d, 1, J ) 15.2), 6.85 (d, 2, J ) 8.6),
6.54 (d, 1, J ) 8.9), 5.51 (d, 1, J ) 5.7), 4.33 (d, 1, J ) 5.7),
1.51 (s, 3), 1.45 (s, 3); 13C NMR (CD3OD) 194.0, 168.2, 163.6,
161.8, 146.2, 135.2, 132.0, 131.9, 127.7, 118.2, 117.7, 116.9 (2
C), 116.2, 103.6, 93.2, 73.1, 70.4, 27.1, 26.5; IR (KBr) 3355,
2935, 1640, 1600, 1576, 1240, 1170; HRMS (DCI/NH3) calcd
for C20H21O6 (MH+) 357.1338, found 357.1345.
Data for 21t: mp 134-136 °C; 1H NMR (CDCl3) 11.63 (s, 1,
OH), 9.69 (s, 1), 7.44 (d, 1, J ) 8.6), 6.51 (d, 1, J ) 8.6), 5.62
(d, 1, J ) 4.3), 5.12 (t, 1, J ) 7.3), 4.51 (d, 1, J ) 4.3), 2.62 (s,
1, OH), 2.15 (dt, 2, J ) 7.3, 7.3), 1.76 (s, OH), 1.67 (s, 3), 1.66-
1.57 (m, 2), 1.62 (s, 3), 1.27 (s, 3); 13C NMR (CDCl3) 194.5,
167.7, 160.4, 137.9, 132.6, 123.8, 116.0, 115.4, 103.6. 97.6, 73.3,
70.3, 37.2, 25.7, 22.4, 21.8, 17.7; IR (KBr) 3324, 2927, 1644,
1252, 1047; Rf (1:1 hexanes/EtOAc) 0.65; HRMS (DCI/NH3)
calcd for C17H23O5 (MH+) 307.1545, found 307.1541.
Data for 6t: mp 229-231 °C; [R]20 -12.2 (c 0.55, MeOH),
D
[R]20 -10.8 (c 0.12, MeOH) {lit.2 [R]22 -0.7 (c 0.06, MeOH),
D
D
1
lit.3 [R]22 -1 (c 0.133, MeOH)}; H NMR (CD3OD) 8.11 (d, 1,
D
J ) 8.9), 7.82 (d, 1, J ) 14.7), 7.64 (d, 1, J ) 14.7), 7.63 (d, 2,
J ) 8.6), 6.85 (d, 2, J ) 8.6), 6.51 (d, 1, J ) 8.9), 5.48 (d, 1, J
) 3.7), 4.38 (d, 1, J ) 3.7), 1.26 (s, 3), 1.25 (s, 3); 13C NMR
(CD3OD) 194.0, 168.9, 164.0, 161.7, 146.0, 135.3, 132.0 (2 C),
127.8, 118.3, 117.0 (2 C), 116.9, 116.0, 103.3, 100.2, 71.9, 71.3,
25.3, 25.2; IR (KBr) 3350, 2975, 1640, 1605, 1566, 1250, 1170;
HRMS (FAB) calcd for C20H21O6 (MH+) 357.1338, found
357.1343.
Data for 22: 1H NMR (CDCl3) 11.90 (s, 1, OH), 9.90 (s, 1),
7.42 (d, 1, J ) 8.5), 7.10 (d, 1, J ) 8.5), 6.82 (s, 1), 5.10 (t, 1,
J ) 7.0), 2.26 (s, 1, OH), 2.01-1.93 (m, 4), 1.63 (s, 6), 1.54 (s,
3); 13C NMR (CDCl3) 196.0, 162.8, 160.2, 157.5, 132.6, 129.6
123.5, 117.9, 115.5, 104.6, 99.5, 72.2, 41.1, 27.0, 25.6, 22.9, 17.7;
Rf (1:1 hexanes/EtOAc) 0.89; HRMS (DCI/NH3) calcd for
C17H19O3 (M+ - OH) 271.1334, found 271.1340.
Data for 23: 1H NMR (CD3OD) 9.95 (s, 1), 7.59 (d, 1, J )
8.5), 6.76 (s, 1), 6.61 (d, 1, J ) 8.5), 5.06 (t, 1, J ) 7.0), 2.00-
1.92 (m, 4), 1.61 (s, 3), 1.56 (s, 3), 1.51 (s, 3); 13C NMR (CD3-
OD) 188.7, 164.0, 162.7, 157.5, 132.4, 131.4, 125.1, 120.0, 114.3,
111.3, 100.0, 72.3, 42.5, 26.6, 25.8, 24.0, 17.6; Rf (1:1 hexanes/
EtOAc) 0.59; HRMS (DCI/NH3) calcd for C17H21O4 (MH+)
289.1440, found 289.1444.
cis-3,4-Dihydroxy-2-(1-hydroxy-1,5-dimethyl-4-hexenyl)-
2,3-dihydrobenzofuran-5-acetophenone (13c) and trans-
3,4-Dihydroxy-2-(1-hydroxy-1,5-dimethyl-4-hexenyl)-2,3-
dihydrobenzofuran-5-acetophenone (13t). A solution of
citral epoxide (11)22 (100 mg, 0.6 mmol), 2,4-dihydroxyac-
etophenone (10) (90 mg, 0.6 mmol), CaCl2 (73 mg, 0.66 mmol),
and KOH (74 mg, 1.32 mmol) in MeOH (6 mL) was stirred at
25 °C for 1 d. The reaction was neutralized with 10% citric
A similar sequence starting with (R)-26 afforded 6c {[R]22
D
-125 (c 0.5, MeOH)} and 6t {[R]22 +9 (c 0.33, MeOH)}.
D
8-(1-Hydroxy-1,5-dimethyl-4-hexenyl)-2H-furo[2,3-h]-
1-benzopyran-2-one (28), trans-8-(1-Hydroxy-1,5-dimeth-
yl-4-hexenyl)-2-oxo-8,9-dihydro-2H-furo[2,3-h]-1-benzopy-
ran-9-acetic Acid Lactone (30) and Methyl trans-8-(1-
Hydroxy-1,5-dimethyl-4-hexenyl)-2-oxo-8,9-dihydro-2H-
furo[2,3-h]-1-benzopyran-9-acetate. A solution of 21t (24
mg, 0.08 mmol) and N,N-dimethylacetamide dimethyl acetal
(0.03 mL, 0.19 mmol) in dry Et2O (1 mL) was stirred for 6 h
at reflux. After cooling, the mixture was neutralized with 10%
HCl to pH 4-5 and extracted with CH2Cl2. The combined
CH2Cl2 extracts were washed with water and saturated
NaHCO3, dried (MgSO4), and concentrated to yield 22 mg
crude product. Purification of the crude product by preparative
1768 J. Org. Chem., Vol. 70, No. 5, 2005