A Versatile Synthesis of O-Desmethylangolensin Analogues from Methoxy-Substituted Benzoic Acids
571
by silica gel column chromatography using 30% EtOAc/
δ 12.72 (s, 1H), 10.67 (s, 1H), 9.37 (s, 1H), 7.86 (d, J = 9.0
Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 6.77 (d, J = 7.7 Hz, 1H),
6.69−6.73 (m, 1H), 6.60 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H),
6.32 (dd, J1 = 8.9 Hz, J2 = 2.3 Hz, 1H), 6.24 (d, J = 2.3 Hz,
1
n-hexane as eluant to give 7bf (802 mg, 89%). H NMR
(300 MHz, CDCl3) δ 7.64 (d, J = 8.7 Hz, 1H), 7.14 (d, J =
8.7 Hz, 2H), 6.78 (d, J = 8.7 Hz, 2H), 6.44 (dd, J1 = 8.7 Hz,
J2 = 2.4 Hz, 1H), 6.36 (d, J = 2.4 Hz, 1H), 4.72 (q, J = 6.9
Hz, 1H), 3.82 (s, 3H), 3.80 (s, 3H), 3.73 (s, 3H), 1.45 (d, J
13
1H), 4.79 (q, J = 6.8 Hz, 1H), 1.36 (d, J = 6.8 Hz, 3H); C
NMR (75 MHz, DMSO-d6) δ 205.0, 165.5, 165.3, 158.0,
13
= 6.9 Hz, 3H); C NMR (75 MHz, CDCl3) δ 201.9, 164.0,
143.7, 133.7, 130.2, 118.7, 114.6, 114.3, 112.2, 108.6, 103.0,
−1
159.9, 158.1, 134.2, 133.0, 129.1, 121.4, 113.8, 105.0, 98.3,
45.9, 19.3; FT-IR (film) 3436 (OH), 1626 (C=O) cm ;Ms
−1
+
m/z (%) 258 (M , 39), 137 (100), 81 (34), 77 (18).
55.4, 55.3, 55.2, 50.3, 19.3; FT-IR (film) 1666 (C=O) cm ;
+
Ms m/z (%) 300 (M , 81), 165 (100), 135 (94), 107 (40),
77 (43).
1-(2,5-Dihydroxyphenyl)-2-(3-hydroxyphenyl)pro-
1
pan-1-one (10): viscous liquid; H NMR (300 MHz, DMSO-
d6) δ 11.39 (s, 1H), 9.41 (s, 1H), 9.17 (s, 1H), 7.20 (d, J =
2.9 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 6.94 (dd, J1 = 8.9 Hz,
J2 = 2.9 Hz, 1H), 6.78 (d, J = 8.9 Hz, 1H), 6.72 (d, J = 7.7
Hz, 1H), 6.59−6.66 (m, 2H), 4.80 (q, J = 6.7 Hz, 1H), 1.36
1-(2,4-Dihydroxyphenyl)-2-(4-hydroxyphenyl)propan-
1-one (12)
To a solution of 7bf (751 mg, 2.5 mmol) in methylene
chloride (12 mL) was slowly added boron tribromide (1 M
o
in CH2Cl2, 10.0 mL, 10.0 mmol) at 0 C. Stirring was con-
13
(d, J = 6.7 Hz, 3H); C NMR (75 MHz, DMSO-d6) δ
tinued for 24 h at room temperature, and then the reaction
was quenched by the slow addition of H2O. After evap-
oration of CH2Cl2, the mixture was poured into 5% NaH-
CO3 solution (30 mL) and was extracted with ethyl acetate
(3×20 mL). The combined organic phases were dried over
MgSO4, filtered, and concentrated in vacuo. The residue
was recrystallized twice from 20% EtOAc/n-hexane to give
206.3, 158.1, 154.6, 149.7, 143.3, 130.3, 124.7, 120.0, 118.9,
118.7, 115.7, 114.7, 114.4, 47.3, 19.4; FT-IR (film) 3441
−1
+
(OH), 1666 (C=O) cm ;Ms m/z (%) 258 (M , 98), 137 (100),
109 (31), 81 (33).
1-(2-Hydroxy-4-methoxyphenyl)-2-(4-methoxyphe-
1
nyl)propan-1-one (11): viscous liquid; H NMR (300
o
12 (581 mg, 90%) as a pale yellow solid. mp 102−103 C
MHz, CDCl3) δ 12.92 (s, 1H), 7.69 (d, J = 8.9 Hz, 1H), 7.21
(d, J = 8.7 Hz, 2H), 6.84 (d, J = 8.7 Hz, 2H), 6.39 (d, J =
2.1 Hz, 1H), 6.35 (dd, J1 = 8.9 Hz, J2 = 2.5 Hz, 1H), 4.59
(q, J = 6.8 Hz, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 1.50 (d, J =
10
o
1
(lit. 103 C); H NMR (300 MHz, DMSO-d6) δ 12.77 (s,
1H), 10.64 (s, 1H), 9.33 (s, 1H), 7.88 (d, J = 9.0 Hz, 1H),
7.13 (d, J = 8.7 Hz, 2H), 6.69 (d, J = 8.7 Hz, 2H), 6.31 (dd,
J1 = 9.0 Hz, J2 = 2.4 Hz, 1H), 6.22 (d, J = 2.4 Hz, 1H), 4.77
13
6.8 Hz, 3H); C NMR (75 MHz, CDCl3) δ 204.9, 166.2,
13
(q, J = 6.6 Hz, 1H), 1.34 (d, J = 6.6 Hz, 3H); C NMR (75
165.9, 158.7, 133.7, 131.9, 128.5, 114.5, 112.9, 107.4, 101.2,
55.4, 55.2, 46.0, 19.1; FT-IR (film) 3436 (OH), 1628 (C=O)
MHz, DMSO-d6) δ 204.9, 165.0, 164.7, 156.1, 133.3, 131.9,
−1
+
cm ;Ms m/z (%) 286 (M , 79), 151 (100), 135 (95), 108 (21),
128.4, 115.5, 111.4, 108.1, 102.5, 44.4, 18.9; FT-IR (KBr)
−1
+
3399 (OH), 1629 (C=O) cm ; Ms m/z (%) 258 (M , 65),
91 (25).
137 (100), 121 (89), 91 (21), 77 (31).
1-(2-Hydroxyphenyl)-2-(3,4-dihydroxyphenyl)pro-
1
pan-1-one (13): viscous liquid; H NMR (300 MHz, DMSO-
1-(2-Hydroxy-4-methoxyphenyl)-2-(3-methoxyphe-
o
1
nyl)propan-1-one (8): mp 70−71 C; H NMR (300 MHz,
CDCl3) δ 12.90 (s, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.22 (t, J
= 7.9 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.82−6.84 (m, 1H),
6.73−6.77 (m, 1H), 6.39 (d, J = 2.5 Hz, 1H), 6.34 (dd, J1 =
8.9 Hz, J2 = 2.5 Hz, 1H), 4.60 (q, J = 6.9 Hz, 1H), 3.78 (s,
d6) δ 12.06 (s, 1H), 8.88 (s, 1H), 8.82 (s, 1H), 7.92 (dd, J1 =
8.0 Hz, J2 = 1.3 Hz, 1H), 7.43−7.48 (m, 1H), 6.84−6.94
(m, 2H), 6.67 (d, J = 2.1 Hz, 1H), 6.65 (d, J = 8.7 Hz, 1H),
6.59 (dd, J1 = 8.1 Hz, J2 = 2.0 Hz, 1H), 4.83 (q, J = 6.7 Hz,
13
1H), 1.35 (d, J = 6.7 Hz, 3H); C NMR (75 MHz, DMSO-d6)
13
3H), 3.77 (s, 3H), 1.52 (d, J = 6.9 Hz, 3H); C NMR (75
δ 207.3, 161.7, 145.9, 144.8, 136.3, 132.6, 131.5, 120.0,
119.4, 119.0, 118.2, 116.4, 115.2, 46.4, 19.3; FT-IR (film)
MHz, CDCl3) δ 204.4, 166.1, 165.9, 160.1, 143.1, 131.9,
129.9, 120.0, 113.5, 112.9, 112.2, 107.5, 101.2, 55.4, 55.2,
−1
+
3437 (OH), 1666 (C=O) cm ; Ms m/z (%) 258 (M , 79),
−1
47.0, 19.0; FT-IR (KBr) 3646 (OH), 1626 (C=O) cm ; Ms m/z
241 (46), 137 (100), 121 (98), 91 (35).
+
(%) 286 (M , 59), 151 (100), 135 (12), 108 (27), 95 (26).
1-(2-Hydroxyphenyl)-2-(3,5-dihydroxyphenyl)propan-
1
1-one (14): viscous liquid; H NMR (300 MHz, DMSO-
1-(2,4-Dihydroxyphenyl)-2-(3-hydroxyphenyl)propan-
1
1-one (9): viscous liquid; H NMR (300 MHz, DMSO-d6)
d6) δ 12.02 (s, 1H), 9.22 (s, 2H), 7.90 (dd, J1 = 8.0 Hz, J2 =
2014, Vol. 58, No. 6