906 J ournal of Natural Products, 2002, Vol. 65, No. 6
Zhao et al.
temperature. Ten milliliters of 1 M HCl was added, and the
solution was extracted with EtOAc (15 mL × 3). The organic
layers were combined and dried (MgSO4). Purification by flash
column afforded 299 mg of 6 (86%). Physical and NMR data
for compound 6 have been reported in an earlier publication.3
Allylic Oxid a tion of 6 by Mn O2. To a stirred suspension
of 105 mg (1.2 mmol) of MnO2 in EtOAc (15 mL) was added
345 mg (1.0 mmol) of 6 in EtOAc (5 mL) at room temperature,
and the solution was stirred for 4 h. After filtration, the eluate
was evaporated to dryness and was partitioned between H2O
(20 mL) and Et2O (60 mL). The organic layer was combined
and dried (MgSO4), and the solvent was evaporated to afford
7 (317 mg, 92%). Physical and NMR data for compound 7 have
been reported in an earlier publication.3
Dea cetyla tion of 12. To a stirred solution of 15.5 g of 12
(50 mmol) in dry DMF (150 mL) was added 20.7 g of K2CO3
(150 mmol) at 0 °C. The solution was stirred for 20 min and
10.85 g (9.9 mL) of geranyl bromide (60 mmol) in dry DMF
(60 mL) was added in 10 min. The solution was stirred for 10
h. After suction filtration, 300 mL of H2O was added. The
mixture was extracted with EtOAc (600 mL), followed by Et2O
(600 mL). The organic layers were combined, washed with
brine (100 mL), and dried (MgSO4). The solution was evapo-
rated, and the residue was subjected to CC (hexane-Et2O, 5:1)
to afford 10.11 g (25 mmol) of 13b (50%) and 5.25 g (14.5 mmol)
of 13a (29%). Also, 925 mg (3.0 mmol) of 12 (6%) was recovered.
4-Ger a n oyl-3,5-d ia cetoxyben zoic a cid m eth yl ester
(13b): gum; 1H NMR (CDCl3, 300 MHz) δ 7.64 (2H, s, H-2,
H-6), 5.42 (1H, brt, J ) 7.0 Hz, H-2′), 5.09 (1H, m, H-6′), 4.59
(2H, d, J ) 7.2 Hz, H-1′), 3.89 (3H, s, CO2Me), 2.36 (3H, s,
OCOCH3), 2.09 (4H, m, H-4′, H-5′), 1.70 (3H, s, H-8′), 1.68 (3H,
s, H-9′), 1.62 (3H, s, H-10′); HREIMS m/z 404.1818 (calcd for
1.64 (3H, s, C-9′), 1.60 (3H, s, C-10′); 13C NMR (CDCl3, 75 MHz)
δ 166.8 (s, C-7), 153.4 (s, C-3, C-5), 141.9 (s, C-1), 141.2 (s,
C-4), 131.6 (s, C-3′), 125.1 (s, C-7′), 123.9 (d, C-6′), 119.9 (s,
C-2′), 109.6 (d, C-2, C-6), 69.4 (t, C-1′), 56.2 (q, OMe-3, OMe-
5), 52.2 (q, CO2Me), 39.6 (t, C-4′), 26.4 (t, C-5′), 25.6 (q, C-8′),
17.6 (q, C-9′), 16.3 (q, C-10′); HREIMS δ 348.1925 (calcd for
C
20H28O5, 348.1937).
4-Ger a n oyl-3,5-d im eth oxyben zyl Alcoh ol (16). To a
stirred suspension of LAH (49 mg, 1.28 mmol) in Et2O (50 mL)
at 0 °C was added a solution of 15 (280 mg, 0.8 mmol) in dry
Et2O (20 mL) under argon atmosphere. The solution was
stirred for 10 min and was quenched by H2O (8 mL). Then 50
mL of 1 N HCl was added, and the mixture was extracted by
Et2O (150 mL). The ether layers were combined and dried
(MgSO4). Evaporation of the solvent followed by PTLC afforded
1
230 mg of 16 (0.72 mmol, 90%): gum; H NMR (CDCl3, 300
MHz) δ 6.62 (2H, brs, H-2, H-6), 5.60 (1H, brt, J ) 7.0 Hz,
H-2′), 5.05 (1H, m, H-6′), 4.69 (2H, brs, H-7), 4.52 (2H, d, J )
7.1 Hz, H-1′), 3.89 (6H, s, OMe-3, OMe-5), 2.10 (4H, m, H-4′,
H-5′), 1.70 (3H, s, H-8′), 1.68 (3H, s, H-9′), 1.63 (3H, s, H-10′);
HREIMS m/z 320.1966 (calcd for C19H28O4, 320.1988).
4-Ger an oyl-3,5-dim eth oxyben zaldeh yde (17). To a stirred
suspension of PCC (225 mg, 1.04 mmol) in CH2Cl2 (30 mL) at
0 °C was added 208 mg of 16 (0.65 mmol) in CH2Cl2 (10 mL).
The solution was stirred at 0 °C for 5 h. The suspension was
filtered and washed by Et2O (60 mL) and partitioned between
Et2O (90 mL) and H2O (30 mL). The ether layers were
combined, dried (MgSO4), and evaporated to afford a residue.
PTLC of the residue afforded finally 178 mg of 17 (0.56 mmol,
1
86%): gum; H NMR (CDCl3, 300 MHz) δ 9.86 (1H, s, H-7),
7.13 (2H, s, H-2, H-6), 5.60 (1H, brt, J ) 6.9 Hz, H-2′), 5.05
(1H, m, H-6), 4.77 (2H, brd, J ) 7.0 Hz, H-1′), 3.94 (6H, s,
OMe-3, OMe-5), 2.04 (4H, m, H-4′, H-5′), 1.64 (3H, s, H-8′),
1.63 (3H, s, H-9′), 1.57 (3H, s, H-10′); 13C NMR (CDCl3, 75
MHz) δ 191.2 (s, C-7), 154.2 (s, C-3, C-5), 142.5 (s, C-1), 142.3
(s, C-4), 131.7 (s, C-3′), 131.8 (s, C-7′), 123.9 (d, C-6′), 119.78
(d, C-2′), 106.6 (d, C-2, C-6), 69.6 (t, C-1′), 56.3 (q, OMe-3, OMe-
5), 39.6 (t, C-4′), 26.4 (t, C-5′), 25.7 (q, C-8′), 17.7 (q, C-9′), 16.4
(q, C-10′); HREIMS m/z 318.1822 (calcd for C19H26O4, 318.1831).
4-Ger a n oylsin a p ic Acid (18). To a stirred solution of
malonic acid (156 mg, 1.5 mmol) in Py (15 mL) at room
temperature was added 475 mg (1.5 mmol) of 17 in Py (10
mL). Piperidine (20 mg) was added to the solution. The mixture
was heated at 120 °C for 4 h. The solvent was evaporated and
dried (MgSO4), evaporated, and followed by CC (CHCl3-
MeOH, 8:1) to afford 463 mg of 18 (1.3 mmol, 86%): gum; 1H
NMR (CDCl3, 400 MHz) δ 7.69 (1H, d, J ) 15.9 Hz, H-7), 6.75
(2H, s, H-2, H-6), 6.34 (d, J ) 15.8 Hz, H-8), 5.53 (1H, brt, J
) 7.2 Hz, H-2′), 5.05 (1H, m, H-6′), 4.57 (2H, brd, J ) 7.1 Hz,
H-1′), 3.87 (6H, s, OMe-3, OMe-5), 2.03 (4H, m, H-4′, H-5′),
1.65 (3H, s, H-8′), 1.64 (3H, s, H-9′), 1.57 (3H, s, H-10′); 13C
NMR (CDCl3, 100 MHz) δ 172.1 (s, C-9), 154.0 (s, C-3, C-5),
147.1 (d, C-7), 141.8 (s, C-4), 139.4 (s, C-1), 131.6 (s, C-3′), 129.4
(s, C-7′), 134.0 (d, C-6′), 120.0 (d, C-2′), 116.2 (d, C-8), 105.5
(d, C-2, C-6), 69.6 (t, C-1′), 56.2 (q, OMe-3, OMe-5), 39.6 (t,
C-4′), 26.4 (t, C-5′), 25.7 (q, C-8′), 17.7 (q, C-9′), 16.4 (q, C-10′);
EIMS m/z 360 [M]+, (3), 345 (1), 331 (11), 316 (3), 224 (100),
209 (4), 198 (26), 181 (4), 69 (23); HREIMS m/z 360.1927 (calcd
for C21H28O5, 360.1937).
C
22H28O7, 404.1835).
4-Ger a n oyl-3-a cetoxy-5-h yd r oxysin a p ic a cid m eth yl
ester (13a ): gum; 1H NMR (CDCl3, 300 MHz) δ 7.52 (1H, brs,
H- 2), 7.36 (1H, brs, H-6), 5.90 (1H, brs, OH-5), exchanged in
D2O), 5.48 (1H, t, J ) 7.0 Hz, H-2′), 5.08 (1H, m, H-6′), 4.63
(1H, d, J ) 7.1 Hz, H-1′), 3.90 (3H, s, CO2Me), 2.36 (3H, s,
OCOCH3), 2.10 (4H, m, H-4′, H-5′), 1.70 (3H, s, H-8′), 1.66 (3H,
s, H-9′), 1.61 (3H, s, H-10′); HREIMS m/z 362.1709 (calcd for
C
20H26O6, 362.1729).
Dea cetyla tion of 13 (13a a n d 13b) (e.g., 13a ). To a stirred
solution of 13a (2.91 g, 8.0 mmol) in MeOH (200 mL) at 0 °C
was added 5.66 g (43.2 mmol) of K2CO3 in H2O (60 mL) in 10
min. The solution was stirred for 20 min, and the solvent was
evaporated. Then 1 M HCl was added to adjust the pH value
to 2, and the aqueous solution was extracted by EtOAc (300
mL). The organic layers were combined and dried (MgSO4),
and the solvent was evaporated to afford 2.32 g (7.2 mmol) of
14 (90%).
4-Ger a n oyl-3,5-h yd r oxyben zoic a cid m eth yl ester (14):
gum; 1H NMR (300 MHz, CDCl3) δ 7.25 (2H, s, H-2, H-6), 5.91
(1H, s, exchanged in D2O, ArOH), 5.60 (1H, brt, J ) 7.0 Hz,
H-2′), 5.09 (1H, m, H-6′), 4.66 (2H, d, J ) 7.1 Hz, H-1′), 3.90
(3H, s, CO2Me), 2.08 (4H, m, H-4′, H-5′), 1.70 (3H, s, H-8′),
1.66 (3H, s, H-9′), 1.61 (3H, s, H-10′); 13C NMR (75 MHz,
CDCl3) δ 166.9 (s, C-7), 149.2 (s, C-3, C-5), 145.2 (s, C-1), 137.4
(s, C-4), 132.1 (s, C-3′), 126.1 (s, C-7′), 123.5 (s, C-6′), 118.7 (s,
C-2′), 109.5 (d, C-2, C-6), 69.9 (t, C-1′), 52.2 (q, CO2Me), 39.6
(t, C-4′), 26.2 (t, C-5′), 25.6 (q, C-8′), 17.7 (q, C-9′), 16.4 (q,
C-10′); HREIMS δ 320.1622 (calcd for C18H24O5, 320.1624).
4-Ger a n oyl-3,5-m eth oxyben zoic a cid m eth yl ester (15).
To a stirred solution of 14 (320 mg, 1.0 mmol) in dry DMF (30
mL) was added 8 mg of K2CO3 (6.0 mmol) at room temperature
under argon, then 0.312 mL (5.0 mmol) of MeI in DMF (5 mL)
was added. The solution was heated at 100 °C for 3 h and was
cooled to 25 °C. After suction filtration, the filtrate was
partitioned between H2O (120 mL) and EtOAc-ether (100 mL/
100 mL). The organic layers were combined and dried (MgSO4).
The solution was evaporated under reduced pressure, and the
residue was subjected to PTLC; 315 mg (0.91 mmol) of 15 was
obtained (91%): gum; 1H NMR (CDCl3, 300 MHz) δ 7.30 (2H,
s, H-2, H-6), 5.55 (1H, brt, J ) 7.0 Hz, H-2′), 5.05 (1H, m, H-6′),
4.59 (1H, d, J ) 7.0 Hz, H-1′), 3.93 (3H, s, H-9′), 3.89 (6H, s,
OMe-3, OMe-5), 2.04 (4H, m, H-4′, H-5′), 1.66 (3H, s, C-8′),
4-Ger a n oyl-7,8-d ih yd r osin a p ic Acid (19). To a stirred
solution of LAH (41 mg, 1.09 mmol) in dry Et2O (15 mL) at 0
°C was added 195 mg (0.54 mmol) of 18 in dry Et2O (10 mL)
under argon. The mixture was stirred for 1 h at 0 °C and was
quenched by H2O (6 mL). Then 1 N HCl (10 mL) was added
and extracted by Et2O (30 mL). The ether layer was dried
(MgSO4), evaporated, and subjected to CC (petroleum ether-
Et2O, 1:2) to afford 150 mg of 7 (0.43 mmol, 80%) and 10 mg
of 19 (0.03 mmol, 5%): gum; 1H NMR (CDCl3, 300 MHz) δ
6.46 (2H, brs, H-2, H-6), 5.58 (1H, brt, J ) 7.0 Hz, H-2′), 5.07
(1H, m, H-6′), 4.55 (2H, brd, J ) 7.0 Hz, H-1′), 3.86 (2H, brt,
J ) 7.6 Hz, H-9), 3.90 (6H, s, OMe-3, OMe-5), 2.79 (2H, brt, J
) 7.6 Hz, H-7), 2.01-1.94 (2H, m, H-8); HREIMS m/z 348.2298
(calcd for C21H32O4, 348.2300).
4-O-Ben zyl-3,5-d ia cetoxyben zoic Acid Meth yl Ester
(21). The method of preparation of 21 was similar to that used