92
A. Saeed
of 4 (0.3 g, 0.91 mmol) in ethanol (30 ml)
and water (75 ml). The reaction mixture
was stirred for 2 h at room temperature,
diluted with water (150 ml), acidified with
conc. HCl, and stirred for a further 2 h.
It was then saturated with ammonium
sulfate, and extracted with EtOAc
(3£ 100 ml). The layers were separated
and the organic layer was dried (MgSO4)
and concentrated. The racemic hydroxy
acid 5a produced in situ underwent
spontaneous cyclization to 5 on standing
for some time (TLC; 0.2 g, 0.063 mmol,
72%). EI-MS m/z (%): 314 [M]þz (56), 178
(100), 147 (14), 118 (42), 90 (59), 89 (15);
IR (film): 2850, 1730, 1710, 1604, 1583,
(MgSO4) and concentrated to afford 6
(68 mg, 0.22 mmol, 71%). IR (film, n,
cm21): 3600, 3375, 2924, 1667, 1622,
1604, 1581, 1464, 1198, 832; EI-MS m/z
(%): 300 [Mþ] (11.45), 238 (37.09), 181
(100), 165 (72.3); 1H NMR (acetone-d6, d,
ppm): 3.20 (1H, dd, J ¼ 16.3, 3.2 Hz, H-
4), 3.32 (1H, dd, J ¼ 16.3, 11.7 Hz, H-4),
3.77 (3H, s, MeO-7), 3.90 (3H, s, MeO-6),
5.65 (1H, dd, J ¼ 11.7, 3.2 Hz, H-3), 6.37
(1H, s, H-5), 7.29 (1H, t, J ¼ 7.8 Hz, H-40),
7.39 (2H, t, J ¼ 8.2 Hz, H-30, 50), 7.51 (2H,
d, J ¼ 8.2 Hz, H-20, 60); 13C NMR
(acetone-d6, d, ppm): 169.8 (C-1), 164.8
(C-6), 158.6 (C-8), 144.0 (C-4a), 107.2
(C-8a), 105.9 (C-5), 136.1 (C-7), 79.8
(C-3), 35.7 (C-4), 140.2 (C-10), 126.7
(C-20, 60), 129.0 (C-40), 129.9 (C-30, 50),
59.7 (MeO-6), 56.8 (MeO-7); Elemental
analysis: Found: C, 67.89%, H, 5.31%;
calcd for C17H16O5: C, 67.99%, H, 5.37%.
1572, 1464, 1198, 832 cm21 1H NMR
;
(300 MHz, CDCl3) d: 3.13–3.08 (1H, dd,
Jgem ¼ 16.5 Hz, Jcis ¼ 3.4 Hz, H-4), 3.26
(1H, dd, Jgem ¼ 16.5 Hz, Jtrans ¼ 12.1 Hz,
H-4), 3.85 (3H, s, MeO-7), 3.89 (3H, s,
MeO-6), 3.94 (3H, s, MeO-8), 5.42 (1H,
dd, J ¼ 12.1, 3.4 Hz, H-3), 6.45 (1H, s,
H-5), 7.21 (1H, t, J ¼ 7.8 Hz, H-40), 7.30
(2H, t, J ¼ 7.2 Hz, H-30, H-50), 7.47 (2H, d,
J ¼ 7.2 Hz, H-20, H-60) ppm; 13C NMR
(CDCl3) d: 171.3 (C-1), 163.0 (C-8), 162.8
(C-6), 144.0 (C-4a), 107.2 (C-8a), 103.9
(C-5), 134.4 (C-7), 78.6 (C-3), 35.6 (C-4),
141.2 (C-10), 126.7 (C-20, 60), 129.3 9
(C-30, 50), 128.9 (C-40), 55.7 (MeO-7), 56.7
(MeO-6), 59.4 (MeO-8); Elemental anal-
ysis: Found: C, 68.91%, H, 5.63%; calcd
for C18H18O5: C, 68.78%, H, 5.77%.
2.6 6,7,8-Trihydroxy-3-phenyl-3,4-
dihydroisocoumarin [(6)-7-
demethylannulatomarin] (7)
Anhydrous AlCl3 was added portionwise to
a stirred solution of 5 (80 mg, 0.22 mmol)
in ethane thiol (1.2 ml, 1.2 mmol) at 08C
and the reaction mixture was stirred further
for 1 h. The reaction mixture was poured
into ice water (20 ml) and extracted with
EtOAc (3£ 50 ml). The combined organic
phase was dried (MgSO4) and concentrated
to afford 7 (44 mg, 0.16 mmol, 65%). IR
(film, n, cm21): 3600, 2924, 1663, 1619,
1604, 1578, 1464, 1198, 831; EI-MS m/z
(%): 272 [Mþ] (11.45), 238 (37.09), 181
(100), 165 (72.3); 1H NMR (acetone-d6, d,
ppm): 3.20 (1H, dd, J ¼ 16.0, 2.9 Hz, H-4),
3.32 (1H, dd, J ¼ 16.0, 11.7 Hz, H-4), 5.65
(1H, dd, J ¼ 11.7, 2.9 Hz, H-3), 6.45 (1H,
s, H-5), 7.29 (1H, t, J ¼ 7.2 Hz, H-40), 7.39
(2H, t, J ¼ 7.2 Hz, H-30, 50), 7.51 (2H, d,
J ¼ 7.2 Hz, H-20, 60) ppm; 13C NMR
(acetone-d6, d, ppm): 169.6 (C-1), 156.4
(C-6), 157.8 (C-8), 144.0 (C-4a), 107.2
(C-8a), 105.9 (C-5), 134.2 (C-7), 79.8 (C-
3), 35.7 (C-4), 140.21 (C-10), 126.7 (C-20,
2.5 8-Hydroxy-6,7-dimethoxy-3-
phenyl-3,4-dihydroisocoumarin [(6)-6-
O-methylannulatomarin] (6)
Anhydrous AlCl3 was added to a stirred
solution of 5 (100 mg, 0.32 mmol) in dry
ether (1.2 ml, 1.2 mmol) under nitrogen.
The reaction mixture was refluxed for 1 h.
The ether was evaporated and the reaction
mixture was poured into ice water (20 ml)
and stirred for 10 min. The layers were
separated and the aqueous layer was
extracted with CH2Cl2 (2£ 50 ml). The
combined organic phase was dried