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M. Gunes, A. Speicher / Tetrahedron 59 (2003) 8799–8802
8801
NMR (CDCl3) d (ppm) 11.01 (s, 1H, OH-8), 7.45–7.31 (m,
8H, Ar-H), 7.00 (d, J¼8.4 Hz, 2H, H-30 and H-50), 6.91 (d,
J¼8.4 Hz, 1H, H-7), 6.72 (d, J¼7.2 Hz, 1H, H-5), 5.51 (dd,
X part of ABX system, JAX¼12.0 Hz, JBX¼3.2 Hz, 1H,
H-3), 5.08 (s, 2H, OCH2Ar), 3.31 (dd, A part of ABX
system, JAB¼16.4 Hz, JAX¼12.0 Hz, 1H, H-4), 3.06 (dd, B
part of ABX system, JAB¼16.8 Hz, JBX¼3.2 Hz, 1H, H-4);
13C NMR (CDCl3) d (ppm) 169.80, 169.29, 159.23,
139.41, 136.72, 136.27, 130.28, 128.61, 128.03, 127.70,
127.42, 117.71, 116.39, 115.09, 108.48, 80.67, 70.10, 34.96;
MS (EI) m/z (%) 346 (5, Mþ), 302 (7), 212 (4), 211 (5), 193
(2), 181 (3), 165 (7), 153 (4), 152 (4), 92 (8), 91 (100), 65
(15).
(5), 160 (4), 149 (5), 134 (25), 91 (18), 85 (47), 83 (71), 47
(23), 45 (60), 43 (100).
3.1.6. (E,Z)-2-(30-Benzyloxy-40-methoxyphenyl)-1-((3-
hydroxy-2-carboxy)phenyl) ethene (5a). To a solution of
the ethyl ester 4a (18.7 g, 46.2 mmol) in EtOH (200 mL)
was added KOH (27.5 g, 0.49 mol). The mixture was heated
to reflux for 24 h, concentrated and treated with water
(250 mL). CH2Cl2 (100 mL) was added and the organic
layer was dispatched. After acidification with concd HCl,
the aqueous layer was extracted with CH2Cl2 (3£200 mL)
and dried (MgSO4). Removing of the solvent and recrys-
tallization of the residue from 1,2-dichloroethane gave
stilbene carboxylic acid 5a (15.8 g, 91%) as yellow needles.
Mp 131–1348C. Anal. calcd for C23H20O5: C, 73.39; H,
3.1.4. 3-(40-Hydroxyphenyl)-8-hydroxy-3,4-dihydrobenzo-
pyran-1-one (hydrangenol) (1). To a solution of the benzyl
protected dihydroisocoumarine 6 (2.10 g, 6.06 mmol) in
EtOAc (100 mL) were added 5% Pd/C (0.50 g). The
mixture was hydrogenated (5 bar, Parr apparatus). The
catalyst was filtered off and the solvent was removed.
Recrystallization from ethanol afforded hydrangenol (1)
(1.30 g, 84%) as colourless needles. Mp 170–1748C (lit.:3
180–1818C). Anal. calcd for C15H12O4C, 70.31; H, 4.72.
1
5.36. Found C, 73.42; H, 5.38; H NMR (DMSO-d6) d
(ppm) 7.47–6.83 (m, 13H, Ar-H and CHv), 5.10 (s, 2H,
OCH2Ar), 3.82 (s, 3H, OCH3); 13C NMR (DMSO-d6) d
(ppm) 170.08, 156.04, 149.29, 147.91, 136.95, 136.54,
130.78, 130.35, 130.29, 128.30, 127.70, 124.52, 119.68,
119.43, 116.31, 114.76, 113.79, 110.07, 69.96, 55.51; MS
(EI) m/z (%) 377 (5, Mþ), 332 (4), 242 (4), 92 (9), 91 (100),
85 (8), 83 (13), 65 (8), 60 (5), 55 (4), 51 (4), 47 (9), 45 (14),
44 (11), 43 (23).
1
Found C, 70.24; H, 4.69; H NMR (DMSO-d6) d (ppm)
10.95 (s, 1H, OH-8), 9.64 (s, 1H, OH-40), 7.500 (dd,
J¼8.0 Hz, 1H, H-6), 7.31 (d, J¼8.4 Hz, 2H, H-2 and
H-60), 6.88 (dd, J¼8.4 Hz, 1H, H-7), 6.85 (d,0J¼7.6 Hz, 1H,
H-5), 6.82 (d, J¼8.4 Hz, 2H, H-30 and H-5 ), 5.62 (dd, X
part of ABX system, JAX¼12.0 Hz, JBX¼2.8 Hz, 1H, H-3),
3.1.7. 3-(30-Benzyloxy-40-methoxyphenyl)-8-hydroxy-
3,4-dihydrobenzopyran-1-one (6a). To a solution of the
stilbene-o-carboxylic acid 5a (8.40 g, 22.3 mmol) in 1,2-
dichloroethane (100 mL) was added trifluoroacetic acid
(15.0 mL) in water (7 mL). The mixture was heated to reflux
for 3 h, evaporation of the solvent and CC of the residue
eluting with EtOAC gave the dihydroisocoumarine 6a
(7.14 g, 85%) as colourless needles. Mp 141–1438C. Anal.
calcd for C23H20O5: C, 73.50; H, 5.36. Found C, 73.60; H,
5.37; 1H NMR (CDCl3) d (ppm) 10.99 (s, 1H, OH-8), 7.44–
7.2 (m, 6H, Ar-H), 7.00 (dd, J¼8.4 Hz, 2H, Ar-H), 6.88 (d,
J¼8.0 Hz, 2H, Ar-H), 6.68 (d, J¼7.4 Hz, 1H, Ar-H), 5.44
(dd, X part of ABX system, JAX¼12.0 Hz, JBX¼3.2 Hz, 1H,
H-3), 5.13 (s, 2H, OCH2Ar), 3.87 (s, 3H, OCH3), 3.25 (dd, A
part of ABX system, JAB¼16.2 Hz; JAX¼12.3 Hz, 1H,
H-4), 3.03 (dd, B part of ABX system, JAB¼16.2 Hz,
JBX¼3.2 Hz, 1H, H-4); 13C NMR (CDCl3) d (ppm) 169.77,
162.25, 150.33, 148.40, 139.36, 136.85, 136.28, 130.34,
128.53, 127.92, 127.43, 119.51, 117.92, 116.33, 112.53,
111.82, 108.42, 80.69, 71.28, 56.06, 34.91; MS (EI) m/z (%)
376 (0.3, Mþ), 242 (0.6), 92 (1), 91 (16), 58 (33), 43 (100),
42 (16).
3.36 (dd, A part of ABX system, JAB¼16.4 Hz, JAX
¼
12.4 Hz, 1H, H-4), 3.10 (dd, B part of ABX system,
JAB¼16.4 Hz, JBX¼2.8 Hz, 1H, H-4); 13C NMR (DMSO-
d6) d (ppm) 169.32, 160.97, 157.79, 140.46, 136.21, 128.41,
128.16, 118.30, 115.39, 115.19, 108.39, 80.44, 33.49; MS
(EI) m/z (%) 256 (45, Mþ), 238 (39), 212 (49), 210 (46), 182
(27), 181 (31), 165 (37), 105 (25), 85 (55), 83 (93), 57 (47),
55 (46), 43 (100), 39 (83).
3.1.5. (E,Z)-2-(30-Benzyloxy-40-methoxyphenyl)-1-((3-
hydroxy-2-ethoxycarbonyl)phenyl) ethene (4a). To a
solution of sodium ethoxide (10.2 g, 0.15 mol) in dry
EtOH (300 mL) was added the phosphonium salt 210
(56.4 g, 0.10 mol) and 3-benzyloxy-4-methoxybenzalde-
hyde (3a) (24.2 g, 0.10 mol) The mixture was heated to
reflux for 24 h, concentrated and treated with water
(150 mL). The organic layer was extracted with CHCl3
(2£100 mL) and dried (MgSO4). Evaporation of the solvent
and CC of the residue eluting with CHCl3 gave the stilbene
4a (37.0 g, 92%) as yellow needles. Mp 91–938C (6:4
mixture of E/Z-stereoisomers). Anal. calcd for C25H24O4: C,
74.24; H, 5.98. Found C, 74.20; H, 5.98; 1H NMR (CDCl3) d
(ppm) 11.38 (s, 0.4H, OH-8), 11.24 (s, 0.6H, OH-8), 7.55–
6.35 (m, 13H, Ar-H and CHv), 5.18 (s, 1.2H, OCH2Ar),
4.77 (s, 0.8H, OCH2Ar), 4.35 (m, 2H, COOCH2CH3), 3.90
(s, 1.8H, OCH3), 3.83 (s, 1.2H, OCH3), 1.31 (m, 3H,
COOCH2CH3); 13C NMR (CDCl3) d (ppm) 171.24, 171.04,
162.74, 162.44, 157.01, 149.94, 148.56, 147.50, 141.43,
137.16, 134.40, 134.26, 132.08, 131.92, 130.90, 130.70,
130.48, 130.06, 129.49, 128.60, 128.43, 127.93, 127.64,
127.56, 127.28, 126.79, 122.71, 122.35, 120.52, 119.48,
116.75, 116.53, 114.68, 112.31, 112.12, 111.68, 111.40,
111.08, 71.34, 70.66, 61.76, 56.14, 55.96, 14.36, 14.01; MS
(EI) m/z (%) 404 (0.6, Mþ), 277 (1), 223 (1), 212 (1), 180
3.1.8. 3-(30-Hydroxy-40-methoxyphenyl)-8-hydroxy-3,4-
dihydrobenzopyran-1-one (phyllodulcin) (1a). To a
solution of the dihydroisocoumarine 6a (4.40 g,
11.7 mmol) in EtOAc (200 mL) was added 5% Pd/C
(0.50 g). The mixture was hydrogenated (5 bar, Parr
apparatus). The catalyst was filtered off and the EtOAc
solution was concentrated. The residue was recrystallized
from EtOH and afforded phyllodulcin (1a) (2.70 g, 81%) as
colourless needles. Mp 128–1298C (lit.:7 128–1308C, lit.:3
118–1208C). Anal. calcd for C16H14O5: C, 67.13; H, 4.93.
1
Found C, 67.05; H, 4.95; H NMR (DMSO-d6) d (ppm)
10.93 (s, 1H, OH-8), 9.14 (s, 1H, OH-50), 7.50 (dd, 1H,
J¼8.0, 7.6 Hz, H-6), 6.96–6.83 (m, 5H, Ar-H), 5.62 (dd,
1H, X part of ABX system, JAX¼11.6 Hz, JBX¼3.2 Hz,
H-3), 3.77 (s, 3H, OCH3), 3.32 (dd, 1H, A part of ABX