PAPER
Biomimetic Synthesis of Dimeric Isorhapontigenin
3825
Stilbene 10
(d, J = 1.6 Hz, 2 H, H-12, 12¢), 7.12 (br s, 2 H, OH), 7.81 (br s, 2 H,
A stirred solution of phosphonium salt 9 (7.2 g, 12.0 mmol) in an-
hyd toluene (80 mL) was added to a solution of n-BuLi (2.4 mL,
12.0 mmol) in n-hexane under argon. After stirring for 30 min, al-
dehyde 8 (2.0 g, 10.0 mmol) was added and the mixture was re-
fluxed under stirring for 2 h. After cooling to r.t., EtOH (20 mL) was
added. The reaction mixture was concentrated and extracted with
EtOAc (150 mL). The EtOAc layer was washed with H2O (150
mL), brine (150 mL), and dried (MgSO4). The solvent was removed
under reduced pressure and the residue purified by CC on silica gel
[petroleum ether (bp 60–90 °C)–EtOAc, 10:1] to give 10 (3.0 g,
91%) as a pale yellow solid; mp 132–134 °C.
1H NMR (300 MHz, CDCl3): d = 1.51 (s, 9 H, t-C4H9), 3.96 (s, 3 H,
OCH3), 5.12 (s, 4 H, CH2Ar), 6.16 (br s, 1 H, OH), 6.59 (t, J = 2.4
Hz, 1 H, H-12), 6.83 (d, J = 2.4 Hz, 2 H, H-10, 14), 6.93 (d,
J = 16.2 Hz, 1 H, H-8), 7.01 (d, J = 2.1 Hz, 1 H, H-2), 7.08 (d,
J = 2.1 Hz, 1 H, H-6), 7.09 (d, J = 16.2 Hz, 1 H, H-7), 7.36–7.51
(m, 10 H, ArH).
OH), 8.09 (br s, 2 H, OH).
13C NMR (100 MHz, acetone-d6): d = 31.3, 35.1, 54.9, 56.4, 60.5,
102.4, 103.4, 109.0, 118.2, 123.1, 133.4, 136.9, 143.6, 147.9, 150.4,
155.3, 159.2.
HRMS (ESI): m/z calcd for C38H42O8 [M + H]+: 627.2952; found:
627.2961.
13
Rf = 0.14 (CH2Cl2–MeOH, 15:1); pale yellow amorphous powder.
IR (neat): 3405, 2956, 2927, 2859, 1696, 1599, 1458, 1426, 1294,
1259, 1141, 1071 cm–1.
1H NMR (400 MHz, acetone-d6): d = 1.25 (s, 9 H, t-C4H9), 1.38 (s,
9 H, t-C4H9), 3.44 (br s, 1 H, H-8), 3.62 (s, 3 H, OCH3), 3.72 (br s,
1 H, H-7¢), 3.75 (s, 6 H, OCH3), 4.15 (br s, 1 H, H-8¢), 4.23 (br s, 1
H, H-7), 6.08 (d, J = 1.6 Hz, 1 H, H-14), 6.17 (d, J = 2.0 Hz, 1 H,
H-14¢), 6.46 (br s, 2 H, H-12, 2¢), 6.52 (br s, 1 H, H-6¢), 6.56 (br s,
1 H, H-12¢), 6.78 (br s, 1 H, H-2), 6.89 (br s, 1 H, H-6), 7.04 (br s,
1 H, OH), 7.14 (br s, 1 H, OH), 7.39 (br s, 1 H, OH), 7.91 (br s, 1 H,
OH), 7.95 (br s, 1 H, OH), 8.01 (br s, 1 H, OH).
13C NMR (100 MHz, acetone-d6): d = 29.6 (3 C), 30.0 (3 C), 35.1,
35.2, 47.9, 50.0, 51.8, 56.2, 56.5, 58.5, 101.8, 104.2, 105.8, 106.8,
109.4, 110.3, 113.5, 118.9, 119.2, 128.0, 134.8, 137.4, 143.5 (2 C),
147.6, 147.7, 147.8, 150.8, 153.1, 155.4, 157.2, 157.9, 158.5, 159.2,
159.3.
13C NMR (75 MHz, CDCl3): d = 29.3 (3 C), 34.6, 56.0, 69.9 (2 C),
101.0, 105.3 (2 C), 105.6, 118.8, 125.7, 127.5 (4 C), 127.9 (3 C),
128.5 (4 C), 129.3, 135.4, 136.8 (2 C), 139.8, 144.4, 146.8, 160.1 (2
C).
FABMS: m/z = 494.5 [M]+.
Coupling Precursor 11
N,N-Dimethylaniline (15.4 mL, 0.12 mol) was added to a well-
stirred solution of stilbene 10 (2.0 g, 4.0 mmol) in anhyd CH2Cl2 (80
mL) at 0 °C. After 5 min, anhyd AlCl3 (3.2 g, 24.0 mmol) was added
to the reaction mixture. After stirring for an additional 4 h at r.t., the
reaction mixture was quenched with H2O (20 mL) at 0 °C and
poured into aq 1.0 M HCl (20 mL). The resulting mixture was ex-
tracted with EtOAc (3 × 40 mL). The combined EtOAc layers were
washed with brine (100 mL) and dried (MgSO4). The solvent was
removed under reduced pressure and the residue purified by CC on
silica gel (CH2Cl2–MeOH, 20:1) to give 11 (0.82 g, 65%) as a pale
yellow solid; mp 118–120 °C.
1H NMR (300 MHz, CDCl3): d = 1.39 (s, 9 H, t-C4H9), 3.81 (s, 3 H,
OCH3), 6.10 (br s, 1 H, OH), 6.30 (t, J = 2.1 Hz, 1 H, H-12), 6.57
(d, J = 2.1 Hz, 2 H, H-10, 14), 6.72 (d, J = 16.5 Hz, 1 H, H-8), 6.84
(d, J = 2.1 Hz, 1 H, H-2), 6.90 (d, J = 16.5 Hz, 1 H, H-7), 6.94 (d,
J = 2.1 Hz, 1 H, H-6).
ESI-HRMS: m/z calcd for C38H42O8 [M + H]+: 627.2952; found:
627.2948.
Dimerization of 11 with FeCl3·6H2O in Benzene–Acetone
A mixture of compound 11 (221 mg, 0.71mmol) and FeCl3·6H2O
(190 mg, 0.71 mmol) was dissolved in a mixture of benzene and
acetone (9.0 mL/4.5 mL) under argon. After stirring at r.t. for 1 h,
the reaction mixture was quenched with H2O (10 mL) and extracted
with EtOAc (20 mL). The EtOAc layer was washed with H2O (20
mL) and brine (20 mL), and dried (MgSO4), and concentrated. The
residue was subjected to CC on silica gel (CH2Cl2–MeOH, 50:1) to
give unreacted 11 (33 mg) and dimer 14 (55.4 mg, 25%).
14
Rf = 0.15 (CH2Cl2–MeOH, 25:1); pale yellow amorphous powder.
13C NMR (75 MHz, CDCl3): d = 29.2 (3 C), 34.5, 56.0, 101.9, 105.7
(2 C), 105.9, 118.7, 125.1, 127.8, 130.0, 135.2, 140.4, 144.3, 146.7,
156.7 (2 C).
HRMS (ESI): m/z calcd for C19H22O4 [M – H]+: 313.1445; found:
313.1450.
IR (neat): 3396, 2957, 2870, 1690, 1600, 1454, 1428, 1297, 1258,
1154, 1068 cm–1.
1H NMR (400 MHz, acetone-d6): d = 1.31 (s, 9 H, t-C4H9), 1.32 (s,
9 H, t-C4H9), 3.82 (s, 6 H, OCH3), 3.83 (s, 3 H, OCH3), 4.51 (d,
J = 6.8 Hz, 1 H, H-8), 5.43 (d, J = 6.8 Hz, 1 H, H-7), 6.27 (d,
J = 2.0 Hz, 1 H, H-12), 6.29 (d, J = 2.0 Hz, 2 H, H-10,14), 6.33 (d,
J = 2.0 Hz, 1 H, H-12¢), 6.67 (d, J = 16.0 Hz, 1 H, H-8¢), 6.74 (br s,
1 H, H-2¢), 6.75 (d, J = 2.0 Hz, 1 H, H-14¢), 6.83 (br s, 1 H, H-6¢),
6.87 (br s, 1 H, H-6), 6.92 (br s, 1 H, H-2), 6.93 (d, J = 16.0 Hz, 1
H, H-7¢), 7.54 (br s, 1 H, OH), 7.56 (br s, 1 H, OH), 8.37 (br s, 2 H,
OH), 8.55 (br s, 1 H, OH).
13C NMR (100 MHz, acetone-d6): d = 29.6 (3 C), 30.5 (3 C), 35.1,
35.2, 56.3, 56.5, 57.4, 94.7, 96.7, 102.1, 103.8, 106.4, 107.3 (2 C),
107.4, 117.4, 119.5, 120.0, 123.3, 128.9, 130.5, 132.2, 135.8 (2 C),
136.2, 145.4, 145.7, 147.2, 148.2, 148.4, 159.5, 159.8 (2 C), 162.4.
Dimerization of 11 with FeCl3·6H2O in Dichloromethane
A mixture of compound 11 (398 mg, 1.27mmol) and FeCl3·6H2O
(343 mg, 1.27 mmol) in anhyd CH2Cl2 (14 mL) was stirred at r.t. un-
der argon for 1 h. After removal of the solvent under reduced pres-
sure, the resulting residue was diluted with EtOAc (30 mL), which
was then washed with H2O (30 mL) and brine (30 mL), and dried
(MgSO4). The solvent was evaporated in vacuo and the residue was
subjected to CC on silica gel (CH2Cl2–MeOH, 40:1) to give two
major dimers 12 (90.6 mg, 23%) and 13 (83.5 mg, 21%).
ESI-HRMS: m/z calcd for C38H42O8 [M + H]+: 627.2952; found:
627.2960.
12
Rf = 0.15 (CH2Cl2–MeOH, 15:1); pale yellow amorphous powder.
IR (neat): 3424, 2957, 2871, 1699, 1599, 1457, 1428, 1258, 1140,
1072 cm–1.
1H NMR (400 MHz, acetone-d6): d = 1.40 (s, 18 H, t-C4H9), 3.76 (s,
6 H, OCH3), 3.91 (br s, 2 H, H-8, 8¢), 4.59 (br s, 2 H, H-7, 7¢), 6.21
(d, J = 1.6 Hz, 2 H, H-14, 14¢), 6.66 (br s, 4 H, H-2, 6, 2¢, 6¢), 6.78
( )-Gneafricanin F (6)
A solution of AlCl3 (0.5 g, 3.75 mmol) in MeNO2 (1 mL) was added
to a solution of compound 12 (48 mg, 0.08 mmol) in anhyd toluene
(5 mL) at 50 °C. The reaction mixture was stirred for 50 min, then
quenched with ice-water (4 mL), and extracted with EtOAc (2 × 20
Synthesis 2010, No. 22, 3822–3826 © Thieme Stuttgart · New York