A facile synthetic approach to prenylated flavanones: First total syntheses of (±)-bonannione A and (±)-sophoraflavanone A

Article abstract of DOI:10.1021/np0001124

A facile and efficient approach for the syntheses of both C-8 and C-6 prenylated flavonoids has been developed that features a highly regioselective prenylation of 2,4,6-trihydroxyacetophenone and regioselective cyclization of prenylated polyhydroxy chalcones. Thus, the first efficient total syntheses of (±)sophoraflavanone A (1) and (±)-bonannione A (2), two naturally occurring geranylated flavanones with antibacterial activities, have been achieved starting from the key intermediate 3 via regioselective cyclization of geranylated tetrahydroxychalcone 4.

Full text of DOI:10.1021/np0001124

196
J . Nat. Prod. 2001, 64, 196-199
A F a cile Syn th etic Ap p r oa ch to P r en yla ted F la va n on es: F ir st Tota l Syn th eses
of (()-Bon a n n ion e A a n d (()-Sop h or a fla va n on e A
Yongqiang Wang, Wenfei Tan, Weidong Z. Li, and Yulin Li*
National Laboratory of Applied Organic Chemistry & Institute of Organic Chemistry, Lanzhou University,
Lanzhou, Gansu 730000, People’s Republic of China
Received March 6, 2000
A facile and efficient approach for the syntheses of both C-8 and C-6 prenylated flavonoids has been
developed that features a highly regioselective prenylation of 2,4,6-trihydroxyacetophenone and regio-
selective cyclization of prenylated polyhydroxy chalcones. Thus, the first efficient total syntheses of (()-
sophoraflavanone A (1) and (()-bonannione A (2), two naturally occurring geranylated flavanones with
antibacterial activities, have been achieved starting from the key intermediate 3 via regioselective
cyclization of geranylated tetrahydroxychalcone 4.
Prenylated flavanones are a unique class of naturally
occurring flavonoids characterized by the presence of a
prenylated side chain (i.e., prenyl, geranyl) in the flavonoid
skeleton. Existing in various traditional medicinal plants,
prenylated flavanones exhibit a wide range of interesting
physiological properties (i.e., hypotensive, antifungal, anti-
bacterial, and antitumor).1,2 It was reported that the
presence of a prenyl or geranyl group led to a remarkable
increase of corresponding bioactivities.3 We have been
interested in the development of a facile and general
synthetic approach to the prenylated flavanones in con-
nection with ongoing studies of flavonoids.
The lack of a general, efficient, and regioselective method
for the introduction of a prenylated side chain and the
appropriate use of protective groups for the phenoxy
functions presents a major challenge for the total synthesis
of this class of natural products. For example, Trost’s
synthesis4,5 of the trimethyl ether of (()-sophoraflavanone
A (1) involved a direct geranylation of a metalated phenoxy
ether derivative. The geranylation method employed by
Fukai et al.6,7 in the syntheses of albanins D and E, two
C-6-geranylated natural flavones, suffered from both low
yields and poor selectivity. A facile and efficient geran-
ylation approach was developed in our laboratory and used
in the total synthesis8 of the C-8 geranylated flavanone,
(()-sophoraflavanone C, via the key geranylated interme-
diate 3.
In continuation of our studies on the synthesis of
prenylated flavanones, herein we report the development
of a facile and selective approach for the synthesis of both
C-8 and C-6 prenylated flavanoids exemplified by the first
total syntheses of (()-sophoraflavanone A (1)9,10 and (()-
bonannione A (2),11 two antibacterial geranylated fla-
vanones isolated from Sophora tomentosa L. and Bonannia
greasa, respectively. The synthesis of the C-6 geranylated
flavanone (()-bonannione A (2) (Scheme 1) commenced
from C-3 geranylated acetophenone (3), which is readily
prepared from 2,4,6-trihydroxyacetophenone by the ger-
anylation method previously reported by us.8 Selective bis-
methoxymethylation of 3 was followed by methylation of
the resulting 4a to give geranylated acetophenone 4b,
which was condensed with p-[(methoxy)methoxy]benzal-
dehyde to afford chalcone 5. Deprotection of methoxymethyl
group by treatment with 3 M HCl led to chalcone 6, which
was cyclized under the usual conditions to give methylated
flavanone 7 (mp 116-118 °C). (()-Boninnione A (2) was
obtained (see Experimental Section) by demethylation of
7 with BBr3 in CH2Cl2 in 92% yield. The synthetic (()-2
showed spectral data as well as melting point and chro-
matographic behavior identical with those previously
reported for (()-boninnione A.11 Using the same approach,
the geranylated hydroxyacetophenone 4a was condensed
with p-[(methoxy)methoxy]benzaldehyde to yield the cor-
responding chalcone 8b, which was deprotected to give
tetrahydroxychalcone 9b (mp 70-71 °C).12 The subsequent
regioselective cyclization afforded the C-6 geranylated
flavanone (()-boninnione A (2) and the C-8 geranylated
flavanone (()-sophoraflavanone A (1) (mp 144-145 °C,
lit.9,10 mp 144-145 °C) in a ratio of 4:1 with a combined
yield of 100%. The cyclization of analogous chalcone 9a
(derived from benzaldehyde and 4a )13 quantitatively pro-
duced a single product that was identified as the C-6
geranylated flavanone (()-10, a natural product isolated
from the seeds of Amorpha fruticosa.14 The remarkable
regioselectivity for the cyclization of the geranylated poly-
hydroxychalcones 9a and 9b may result from the presence
of the geranyl group, which would lead to a greater
tendency for the formation of intramolecular hydrogen
bonding of C-2′ phenoxy over C-6′ phenoxy with the
carbonyl group (Scheme 2). The result, to some extent, is
analogous to the well-known Wessely-Moser rearrange-
* Corresponding author: Tel: +86-931-8912595. Fax: +86-931-8912283.
E-mail: liyl@lzu.edu.cn.
10.1021/np0001124 CCC: $20.00
© 2001 American Chemical Society and American Society of Pharmacognosy
Published on Web 01/18/2001

Prenylated Flavanones
J ournal of Natural Products, 2001, Vol. 64, No. 2 197
Sch em e 3a
Sch em e 1a
a
Reagents and conditions: (a) NaOAc, EtOH, reflux; (b) 3 M HCl, MeOH,
reflux.
flavanoids (()-1 and (()-2. The new method will greatly
facilitate the synthesis of prenylated flavanoids and their
analogues for further physiological evaluations.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Melting points were
measured on a Kofler hot stage and are uncorrected. For
column chromatography, 200-300 mesh silica gel was used.
1H and 13C NMR spectra were recorded on a Bruker AM-400
or AC-80 instrument in CDCl3 unless otherwise noted. Chemi-
cal shifts were reported in ppm units with TMS as the internal
standard. IR spectra were obtained on a FT-170-SX spectrom-
eter. LRMS were measured on a ZAB-HS spectrometer by
direct inlet at 70 eV. HRMS were determined on a Bruker
Daltonics APEXII 47e Fourier transform spectrometer with
either EI, CI, FAB, or SIMS ionization methods. 3-Geranyl-
2,4,6-trihydroxyacetophenone (3) was prepared according to
our previously described procedure.8
a
Reagents and conditions: (a) MOMCl, K2CO3, Me2CO, reflux; (b)
(CH3)2SO4, n-Bu4N+I-, NaOH, CH2Cl2-H2O (v/v 3:2), 23 °C; (c) (p-
MOMO)C6H4CHO, KOH, H2O-EtOH (v/v 1:1), 0-23 °C; (d) 3 M HCl,
MeOH, reflux; (e) NaOAc, EtOH, reflux; (f) BBr3, CHCl2, -78 to 23 °C.
Sch em e 2a
4,6-Bis[(methoxy)methoxy]-2-hydroxy-3-(1′-geranyl)aceto-
p h en on e (4a ). To a stirred mixture of 3 (304 mg, 1 mmol)
and anhydrous K2CO3 (966 mg, 7 mmol) in dry acetone (20
mL) was added dropwise MOMCl (200 mg, 25 mmol). The
mixture was heated at reflux for 45 min, then cooled to room
temperature, filtered, and evaporated under reduced pressure.
The resulting residue was purified by silica gel column
chromatography eluting with petroleum ether-EtOAc (6:1) to
afford 4a (279 mg, 71% yield) as a deep red gum: UV (CH3OH)
λmax (log ꢀ) 225 (4.16), 285 (4.18), 328 (3.48) nm; IR (KBr) ν
2967, 2918, 1617, 1486, 1428, 1406, 1373, 1273, 1231, 1152,
1
1107, 1070, 1044, 962 cm-1; H NMR (80 MHz) δ 1.57, 1.64,
1.78 (3H each s, 8′-CH3, 9′-CH3, and 10′-CH3), 1.90-2.30 (4H,
m, 4′-2H and 5′-2H), 2.65 (3H, s, COCH3), 3.31 (2H, d, J ) 6.9
Hz, 1′-2H), 3.47, 3.51 (3H each s, 2 OCH3), 4.90-5.48 (6H, m,
2 OCH2O, 2′-H and 6′-H), 6.40 (1H, s, ArH), 13.84 (1H, s, OH);
EIMS m/z [M+] 392 (4), 347 (10), 273 (7), 269 (3), 225 (3), 69
(10), 45 (100).
4,6-Bis[(methoxy)methoxy]-2-methoxy-3-(1′-geranyl)aceto-
p h en on e (4b). To a well-stirred mixture of 4a (392 mg, 1
mmol), NaOH (60 mg, 1.5 mmol), and (n-C4H9)4N+I- (47 mg,
0.1 mmol) in CH2Cl2-H2O (15 mL, v/v ) 3:2) was added
dropwise (CH3)2SO4 (151 mg, 1.2 mmol). After the mixture was
stirred for 3 h at ambient temperture, the layers were
separated, and the aqueous layer was extracted with CH2Cl2
(3 × 5 mL). The combined CH2Cl2 layers were washed with
H2O and brine, dried over anhydrous MgSO4, and evaporated
under reduced pressure. The residue was purified by silica gel
column chromatography eluting with petroleum ether-EtOAc
(4:1) to give 4b (403 mg, 99% yield) as a deep red gum: UV
(CH3OH) λmax (log ꢀ) 231 (3.81), 262 (3.52) nm; IR (KBr) ν 2932,
1625, 1470, 1432, 1352, 1223, 1109, 1017, 1038 cm-1; 1H NMR
(80 MHz) δ 1.58, 1.65, 1.77 (3H each s, 8′-CH3, 9′-CH3, and
10′-CH3), 1.90-2.15 (4H, m, 4′-2H and 5′-2H), 2.53 (3H, s,
COCH3), 3.31 (2H, d, J ) 6.8 Hz, 1′-2H), 3.48, 3.72, 3.97 (3H
each s, 3 OCH3), 4.80-5.30 (6H, m, 2 OCH2O, 2′-H and 6′-H),
5.30 (1H, br, J ) 6.5 Hz, 2′-H), 6.72 (1H, s, ArH); EIMS m/z
[M+] 406 (3), 36 (10), 287 (2), 283 (2), 239 (5), 91 (30), 69 (45),
45 (100).
a
Reagents and conditions: (a) PhCHO or (p-MOMO)C6H4CHO, KOH,
H2O-EtOH (v/v 1: 1), 0-23 °C; (b) 3 M HCl, MeOH, reflux; (c) NaOAc, EtOH,
reflux.
ment15,16 of corresponding flavones under acidic conditions.
In this case, the predominant production of the C-6
geranylated flavanones over C-8 ones is a result of a
thermodynamically controlled process. The present syn-
thetic method provides a selective and efficient route for
the synthesis of C-6 prenylated natural flavanoids.
Furthermore, we envisioned that the chalcone 8b might
serve as a precursor for the synthesis of C-8 geranylated
flavanones. Thus, cyclization of 8b (performed as usual by
treatment with NaOAc in EtOH) was followed by demeth-
oxymethylation to give (()-sophoraflavanone A (1) in 84%
yield. The synthetic product has identical spectral data
with those of the natural product.15,16 In conclusion, this
facile and efficient approach for the syntheses of C-6 and
C-8 prenylated flavanones features a prenylation of phe-
noxy acetophenone and regioselective cyclization of pren-
ylated hydroxychalcones, which has been exemplified by
the first efficient total syntheses of geranylated natural
4,4′,6′-Tr is[(m eth oxy)m eth oxy]-2′-m eth oxy-3′-(1′′-ger a -
n yl)ch a lcon e (5). To a stirred mixture of potassium hydroxide
(1.0 g, 17.8 mmol) in H2O-EtOH (2 mL, v/v ) 2:3) cooled to 0
°C in an ice bath was added dropwise a solution of 4b (406

198 J ournal of Natural Products, 2001, Vol. 64, No. 2
Wang et al.
mg, 1 mmol) and p-methoxymethoxybenzaldehyde (166 mg, 1
mmol, prepared from p-hydroxybenzaldehyde) in EtOH (2 mL)
cooled to 0 °C under argon. The reaction mixture was kept in
the ice bath for 3 h, then at ambient temperature for 40 h.
The resulting mixture was poured into ice water (5 mL), and
the solution was adjusted to pH 3-4 with 2 M HCl, then
extracted with Et2O (3 × 5 mL). The combined organic layers
were washed with H2O and saturated brine, dried over
anhydrous MgSO4, and evaporated under reduced pressure.
The residue was purified by silica gel column chromatography
eluting with petroleum ether-EtOAc (10:1) to give chalcone
5 (435 mg, 78% yield) as a red liquid: UV (CH3OH) λmax (log
ꢀ) 219 (4.31), 327 (4.33) nm; IR (KBr) ν 2923, 1645, 1599, 1511,
1448, 1420, 1317, 1282, 1230, 1156, 1069, 961 cm-1; 1H NMR
(80 MHz) δ 1.61, 1.68, 1.82 (3H each s, 8′′-CH3, 9′′-CH3, and
10′′-CH3), 1.90-2.30 (4H, br, 4′′-2H and 5′′-2H), 3.38 (2H, d, J
) 7.0 Hz, 1′′-2H), 3.52, 3.55 (3H each s, 2 OCH3), 4.90-5.50
(6H, m, 2 OCH2O, 2′′-H and 6′′-H), 6.43 (1H, s, 5′-H), 7.20-
7.75 (5H, m, Ph), 7.86 (1H, s, Hâ), 7.90 (1H, s, HR), 13.83 (1H,
s, OH); EIMS m/z [M+] 480 (1), 435 (6), 403 (1), 347 (2), 325
(4), 273 (4), 131 (48), 69 (16), 45 (100).
4,4′,6′-Tr is[(m eth oxy)m eth oxy]-2′-h yd r oxy-3′-(1′′-ger a -
n yl)ch a lcon e (8b). Following the same procedure as the
preparation of5,4a was condensed with p-methoxymethoxybenz-
aldehyde to afford chalcone 8b as a red oil in 76% yield: UV
(CH3OH) λmax (log ꢀ) 219 (4.56), 336 (4.57) nm; IR (KBr) ν 2925,
1643, 1599, 1511, 1447, 1421, 1379, 1314, 1237, 1153, 1072,
1
1425, 1316, 1297, 1151, 1072, 995 cm-1; H NMR (80 MHz) δ
1.59, 1.66, 1.78 (3H each s, 8′′-CH3, 9′′-CH3, and 10′′-CH3),
1.90-2.40 (4H, m, 4′′-2H and 5′′-2H), 3.34 (2H, d, J ) 6.5 Hz,
1′′-2H), 3.41, 3.49, 3.51, 3.71 (3H each s, 4 OCH3), 4.90-5.20
(8H, m, 3 OCH2O, 2′′-H and 6′′-H), 6.41(1H, s, 5′-H), 6.77 (1H,
s, Hâ), 6.90-7.20 (2H, m, 3-H, 5-H), 7.40-7.70 (2H, m, 2-H,
6-H), 7.81 (1H, s, HR); EIMS m/z [M+] 554 (0.3), 509 (0.4), 495
(0.7), 431 (0.7), 399 (1), 387 (1), 341 (2), 313 (1), 269 (2), 223
(3), 191 (15), 161 (4), 69 (11), 45 (100); HRMS (EI) m/z calcd
for C32H42O8 554.2864, found for [M+] 554.2854.
996 cm-1 1H NMR (80 MHz) δ 1.59, 1.66, 1.78 (3H each s,
;
8′′-CH3, 9′′-CH3, and 10′′-CH3), 1.90-2.30 (4H, m, 4′′-2H and
5′′-2H), 3.10-3.85 (11H, m, 1′′-2H and 3 OCH3), 4.90-5.40 (8H,
m, 3 OCH2O, 2′′-H and 6′′-H), 6.41 (1H, s, 5′-H), 6.70-7.90
(6H, m, HR , Hâ, 2-H, 3-H, 5-H, 6-H), 13.86 (1H, s, OH); EIMS
m/z [M+] 540 (0.4), 395 (3), 417 (2), 385 (4), 331 (3), 263 (2),
231 (3), 191 (18), 161 (5), 69 (11), 45 (100); HRMS (ESI) m/z
calcd for C31H40O8Na 563.2605, found for [M + Na]+ 563.2617.
2′,4′,6′-Tr ih yd r oxy-3′-(1′′-ger a n yl)ch a lcon e (9a ). Follow-
ing the same procedure as the preparation of 6, 9a was
obtained as amorphous reddish solids (10% EtOAc in petro-
leum ether) in 88% yield: mp 122-124 °C; UV (CH3OH) λmax
(log ꢀ) 219 (4.24), 302 (4.05), 343 (4.12) nm; IR (KBr) ν 3306,
4,4′,6′-T r ih y d r o x y -2′-m e t h o x y -3′-(1′′-g e r a n yl)c h a l-
con e (6). To a stirred solution of 5 (277 mg, 0.5 mmol) in
MeOH (10 mL) was added dropwise 3 M HCl (2 mL). The
solution was heated at reflux for 45 min, then H2O (10 mL)
was added, and the solution was extracted with EtOAc. The
combined organic layers were washed with H2O and brine,
dried over anhydrous MgSO4, and evaporated under reduced
pressure. The residue was purified by silica gel column
chromatography eluting with petoleum ether-EtOAc (10:1) to
give chalcone 6 (131 mg, 62% yield) as a yellow gum: UV
(CH3OH) λmax (log ꢀ) 218 (4.13), 369 (3.96) nm; IR (KBr) ν 3368,
2930, 1623, 1604, 1547, 1512, 1442, 1352, 1228, 1170, 1075,
2917, 1626, 1499, 1451, 1345, 1288, 1232, 1138, 1080 cm-1
;
1H NMR (80 MHz) δ 1.62, 1.69, 1.84 (3H each s, 8′′-CH3, 9′′-
CH3, and 10′′-CH3), 1.95-2.40 (4H, br, 4′′-2H and 5′′-2H), 3.41
(2H, d, J ) 7.1 Hz, 1′′-2H), 4.90-5.50 (2H, m, 2′′-H, 6′′-H),
5.98 (1H, s, 5′-H), 6.73 (1H, br, OH), 7.15-7.70 (5H, m, Ph),
7.88 (1H, s, Hâ), 8.01 (1H, s, HR), 9.46 (1H, br, OH), 11.79 (1H,
br, OH); EIMS m/z [M+] 392 (12), 349 (3), 323 (6), 307 (12),
269 (86), 219 (100), 165 (69), 69 (58), 41 (53).
1
1031 cm-1; H NMR (400 MHz) δ 1.59, 1.67, 1.82 (3H each s,
4,2′,4′,6′-Tetr a h yd r oxy-3′-(1′′-ger a n yl) ch a lcon e (9b).
Following the same procedure as the preparation of 6, 9b was
obtained as amorphous reddish solids (10% EtOAc in petro-
leum ether) in 72% yield: mp 70-71 °C; UV (CH3OH) λmax
(log ꢀ) 219 (4.22), 355 (4.25) nm; IR (KBr) ν 3275, 2923, 1700,
1623, 1604, 1514, 1440, 1344, 1230, 1169, 1082 cm-1; 1H NMR
(400 MHz, DMSO-d6) δ 1.51, 1.58, 1.68 (3H each s, 8′′-CH3,
9′′-CH3, and 10′′-CH3), 1.70-2.05 (4H, m, 4′′-2H and 5′′-2H),
3.09 (2H, d, J ) 7.1 Hz, 1′′-2H), 5.02 (1H, t, J ) 6.8 Hz, 6′′-H),
5.12 (1H, t, J ) 7.1 Hz, 2′′-H), 6.04 (1H, s, 5′-H), 6.82 (2H, d,
J ) 8.4 Hz, 3-H, 5-H), 7.50 (2H, d, J ) 8.4 Hz, 2-H, 6-H), 7.64
(1H, d, J ) 15.6 Hz, Hâ), 7.98 (1H, d, J ) 15.6 Hz, HR), 10.07
(1H, s, 4-OH),10.36 (1H, s, 4′-OH), 10.66 (1H, s, 6′-OH), 14.53
(1H, s, 2′-OH); EIMS m/z [M+] 408 (19), 365 (3), 339 (6), 323
(11), 285 (89), 245 (6), 219 (100), 165 (92), 91 (28), 69 (67), 41
(68).
(()-5,7-Dih yd r oxy-6-(1′′-ger a n yl)fla va n on e (10). Fol-
lowing the same procedure as the preparation of 7, 9a was
cyclized to afford 10 in 99% yield as amorphous solids (15%
EtOAc in petroleum ether): mp 144-145 °C; UV (CH3OH) λmax
(log ꢀ) 227 (4.31), 293 (4.33), 334 (3.62) nm; IR (KBr) ν 3150,
2912, 1631, 1584, 1445, 1298, 1225, 1177, 1083 cm-1; 1H NMR
(400 MHz) δ 1.61, 1.69, 1.82 (3H each s, 8′′-CH3, 9′′-CH3, and
10′′-CH3), 2.00-2.17 (4H, m, 4′′-2H and 5′′-2H), 2.82 (1H, dd,
J ) 2.9, 17.1 Hz, H3â), 3.09 (1H, dd, J ) 13.0, 17.1 Hz, H3R),
3.38 (2H, d, J ) 7.1 Hz, 1′′-2H), 5.06 (1H, t, J ) 5.8 Hz, 6′′-H),
5.24 (1H, t, J ) 7.1 Hz, 2′′-H), 5.40 (1H, dd, J ) 2.9, 13.0 Hz,
2-H), 6.04 (1H, s, 8-H), 6.74 (1H, s, 7-OH), 7.39-7.47 (5H, m,
2′, 3′, 4′, 5′, 6′-5H), 12.38 (1H, s, 5-OH); 13C NMR (CDCl3) 195.9
(C4), 164.1 (C7), 161.2 (C5), 161.0 (C9), 139.0 (C3”), 138.5 (C8′′),
132.0 (C1′), 128.8 (C3′,4′,5′), 126.1 (C2′,6′), 123.7 (C7′′), 121.3 (C2′′),
107.1 (C6), 102.9 (C10), 95.6 (C8), 78.9 (C2), 43.4 (C3), 39.7 (C5′′),
26.3 (C6′′), 25.6 (C10′′), 21.0 (C1′′), 17.7 (C9′′), 16.1 (C4′′); EIMS
m/z [M+] 392 (7), 307 (7), 269 (60), 219 (54), 165 (56), 123 (20),
121 (12), 84 (100), 69 (57), 41 (39).
8′′-CH3, 9′′-CH3, and 10′′-CH3), 1.95-2.16 (4H, m, 4′′-2H and
5′′-2H), 3.39 (2H, d, J ) 6.7 Hz, 1′′-2H), 3.67 (3H, s, OCH3),
5.05 (1H, br, 6′′-H), 5.23 (1H, m, 2′′-H), 6.04 (1H, s, 5′-H), 6.27
(1H, s, OH), 6.88 (2H, d, J ) 8.5 Hz, 3-H, 5-H), 7.55 (2H, d, J
) 8.5 Hz, 2-H, 6-H), 7.83 (2H, s, HR, Hâ), 12.01 (1H, s, OH),
13.36 (1H, s, OH); EIMS m/z [M+] 422 (7), 391 (1), 353 (7),
299 (34), 285 (19), 233 (35), 219 (26), 179 (88), 165 (26), 69
(96), 41(100); HRMS (EI, negative SIMS, NBA) m/z calcd for
C
26H29O5 421.2005, found for [M - H]- 421.2028.
4′,7-Dih yd r oxy-5-m eth oxy-6-(1′′-ger a n yl)fla va n on e (7).
To a solution of 6 (55 mg, 0.13 mmol) in EtOH (1 mL) were
added NaOAc (41 mg, 0.5 mmol) and H2O (one drop). The
mixture was heated at reflux for 24 h. After the mixture was
cooled to ambient temperature, H2O (5 mL) was added and
the mixture was extracted with Et2O (3 × 5 mL). The combined
organic layers were washed with H2O and brine, dried over
anhydrous MgSO4, and evaporated under reduced pressure.
The residue was purified by silica gel column chromatography
eluting with petroleum ether-EtOAc (15:1) to give flavanone
7 (42 mg, 76% yield) as colorless needles (10% EtOAc in
petroleum ether), mp 116-118 °C; UV (CH3OH) λmax (log ꢀ)
229 (4.35), 282 (4.18) nm; IR (KBr) ν 3337, 2926, 1652, 1595,
1517, 1454, 1435, 1334, 1274, 1168, 1082 cm-1; 1H NMR (400
MHz) δ 1.59, 1.66, 1.80 (3H each s, 8′′-CH3, 9′′-CH3, and 10′′-
CH3), 1.97-2.13 (4H, m, 4′′-2H and 5′′-2H), 2.76 (1H, dd, J )
2.6, 16.8 Hz, H3â), 3.01 (1H, dd, J ) 13.2, 16.8 Hz, H3R), 3.39
(2H, d, J ) 6.9 Hz, 1′′-2H), 3.84 (3H, s, OCH3), 5.04 (1H, t, J
) 5.7 Hz, 6′′-H), 5.20 (1H, t, J ) 6.9 Hz, 2′′-H), 5.31 (1H, dd,
J ) 2.6, 13.2 Hz, 2-H), 6.31 (1H, s, 8-H), 6.78 (1H, br, OH),
6.88 (2H, d, J ) 8.3 Hz, 3′-H, 5′-H), 7.28 (2H, d, J ) 8.3 Hz,
2′-H, 6′-H); EIMS m/z [M+] 422 (9), 353 (10), 299 (46), 233 (35),
203 (14), 179 (100), 123 (17), 91 (30), 69 (94), 41 (91); EIHRMS
(negative SIMS, NBA) m/z calcd for C26H29O5 421.2005, found
for [M - H]- 421.2014.
4′,6′-Bis[(m eth oxy)m eth oxy]-2′-h yd r oxy-3′-(1′′-ger a n yl-
)ch a lcon e (8a ). Following the same procedure as the prepara-
tion of 5, 4a was condensed with benzaldehyde to afford
chalcone 8a in 81% yield as an oil: UV (CH3OH) λmax (log ꢀ)
219 (4.23), 356 (4.34) nm; IR (KBr) ν 2920, 1694, 1616, 1583,
5,7,4′-T r is [(m e t h o x y )m e t h o x y ]-8-(1′′-g e r a n y l)fla -
va n on e (12). Following the same procedure as the preparation
of 7, 8b was cyclized to afford 12 in 90% yield (based on
recovered starting material), as amorphous yellowish solids
(15% EtOAc in petroleum ether): mp 40-41 °C; UV (CH3OH)

Prenylated Flavanones
J ournal of Natural Products, 2001, Vol. 64, No. 2 199
λmax (log ꢀ) 227 (4.30), 281 (4.10), 320 (3.56) nm; IR (KBr) ν
(C2), 43.2 (C3), 39.7 (C5′′), 26.3 (C6′′), 25.7 (C10′′), 21.1 (C1′′), 17.7
(C9′′), 16.2 (C4′′); EIMS m/z [M+] 408 (19), 285 (68), 219 (100),
203 (21), 165 (94), 121 (22), 107 (18), 69 (85), 41 (40).
2914, 1682, 1599, 1515, 1445, 1336, 1270, 1233, 1154, 1073,
1
1000 cm-1; H NMR (400 MHz) δ 1.57 (3H, s, 8′′-CH3), 1.64
(6H, s, 9′′-CH3 and 10′′-CH3), 1.90-2.07 (4H, m, 4′′-2H and
5′′-2H), 2.80 (1H, dd, J ) 2.9, 16.5 Hz, H3â), 2.99 (1H, dd, J )
12.8, 16.5 Hz, H3R), 3.32 (2H, d, J ) 7.0 Hz, 1′′-2H), 3.48, 3.50,
3.54 (3H each s, 3 OCH3), 5.06 (1H, t, J ) 7.0 Hz, 2′′-H), 5.21,
5.24, 5.27 (2H, each s, 3 OCH2O), 5.36 (1H, dd, J ) 2.9, 12.8
Hz, 2-H), 6.58 (1H, s, 6-H), 7.08 (1H, d, J ) 8.5 Hz, 3′-H, 5′-
H), 7.38 (2H, d, J ) 8.5 Hz, 2′-H, 6′-H); EIMS m/z [M+] 540
(1), 495 (2), 417 (8), 395 (1), 385 (11), 373 (5), 331 (11), 307
(11), 209 (8), 191 (26), 165 (7), 69 (19), 45 (100); HRMS (EI)
m/z calcd for C31H40O8 540.2707, found for [M+] 540.2711.
(()-Sop h or a fla va n on e A (1). Following the same proce-
dure as the preparation of 6, 12 was deprotected to afford 1
as amorphous solids (20% EtOAc in petroleum ether) in 84%
yield: mp 144-145 °C; UV (CH3OH) λmax (log ꢀ) 226 (4.28),
294 (4.25), 337 (3.62) nm; IR (KBr) ν 3451, 3313, 2937, 1634,
1588, 1510, 1435, 1373, 1341, 1212, 1155, 1059 cm-1; 1H NMR
(80 MHz) δ 1.60, 1.69, 1.72 (3H each s, 8′′-CH3, 9′′-CH3, and
10′′-CH3), 1.90-2.40 (4H, m, 4′′-2H and 5′′-2H), 2.85-3.15 (2H,
m, H3R H3â), 3.33 (2H, d, J ) 7.3 Hz, 1′′-2H), 4.85-5.50 (3H, t,
2-H, 6′′-H, 2′′-H), 6.05 (1H, s, 6-H), 6.89 (2H, d, J ) 8.6 Hz,
3′-H, 5′-H), 7.34 (2H, d, J ) 8.6, 2′-H, 6′-H), 12.00 (1H, s, 5-OH);
13C NMR (CDCl3) 196.5 (C4), 164.0 (C7), 162.2 (C5), 159.7 (C4′),
156.0 (C9), 138.8 (C3′′), 132.0 (C8′′), 130.8 (C1′), 127.7 (C2′,6′),
123.7 (C7”), 121.4 (C2′′), 115.6 (C3′,5′), 106.2 (C6), 103.1 (C10), 97.0
(C8), 78.7 (C2), 43.1 (C3), 39.7 (C5′′),26.3 (C6′′), 25.7 (C10′′), 21.7
(C1′′), 17.7 (C9′′), 16.1 (C4′′); EIMS m/z [M+] 408 (9), 285 (96),
219 (100), 205 (13), 203 (11), 165 (84), 120 (23), 107 (13), 69
(64), 41 (62).
(()-Bon a n n ion e A (2). To a well-stirred solution of 7 (21
mg, 0.05 mmol) in CH2Cl2 (3 mL) at -78 °C was added
dropwise BBr3 (4.7 µL, 13 mg, 0.05 mmol). The mixture was
stirred at -78 °C for 1 h, then slowly warmed to ambient
temperature and stirred for an additional 2 h. The reaction
was quenched by the addition of H2O (5 mL). The layers were
separated, and the aqueous layer was extracted wih CH2Cl2
(3 × 5 mL). The combined organic layers were washed with
H2O and brine, dried over anhydrous MgSO4, and evaporated
under reduced pressure. The resulting residue was purified
by silica gel column chromatography eluting with petroleum
ether-EtOAc (4:1) to give flavanone 2 (19 mg, 93% yield) as
amorphous solids (20% EtOAc in petroleum ether): mp 119-
120 °C; UV (CH3OH) λmax (log ꢀ) 227 (4.44), 294 (4.32), 332
(3.65) nm; IR (KBr) ν 3387, 2923, 1638, 1598, 1517, 1492, 1451,
1340, 1309, 1221, 1152, 1087 cm-1; 1H NMR δ 1.60, 1.69, 1.82
(3H each s, 8′′-CH3, 9′′-CH3, and 10′′-CH3), 2.00-2.15 (4H, m,
4′′-2H and 5′′-2H), 2.79 (1H, dd, J ) 2.9, 17.1 Hz, H3â), 3.09
(1H, dd, J ) 12.8, 17.1 Hz, H3R), 3.43 (2H, d, J ) 7.1 Hz, 1′′-
2H), 5.06 (1H, t, J ) 5.8 Hz, 6′′-H), 5.27 (1H, t, J ) 7.1 Hz,
2′′-H), 5.34 (1H, dd, J ) 2.9, 12.8 Hz, 2-H), 6.00 (1H, s, 8-H),
6.35 (1H, br, OH), 6.89 (2H, d, J ) 8.4 Hz, 3′-H, 5′-H), 7.33
(2H, d, J ) 8.4 Hz, 2′-H, 6′-H), 12.42 (1H, s, OH); 13C NMR
(CDCl3) 196.2 (C4), 164.1 (C7), 161.2 (C5), 161.1 (C4′), 156.1 (C9),
139.5 (C3′′), 132.1 (C8′′), 130.7 (C1′), 127.9 (C2′,6′), 123.7 (C7′′),
121.3 (C2′′), 115.6 (C3′,5′), 106.8 (C6), 102.9 (C10), 95.7 (C8), 78.8
Following a procedure similar to that for the preparation
of 7, 9b was cyclized to afford (()-1 in 20% yield and (()-2 in
80% yield. The spectral data (MS, NMR, IR) of synthetic (()-1
and (()-2 were identical with those of the natural products,
respectively.17
Ack n ow led gm en t. This work was financially supported
by the National Natural Science Foundation of China (No.
29472044).
Refer en ces a n d Notes
(1) (a) Hnawia, E.; Thoison, O.; Gueritte-Voegelein, F.; Bourret, D.;
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Y.; Nomura, T. Heterocycles 1989, 29, 195-202. (c) Phillips, W. R.;
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1986, 14, 195-198. (e) Yakushijin, K.; Shibayama, K.; Murata, H.;
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L.; Fullas, F.; McGivney, R. J .; Brown, D. M.; Wani, M. C.; Wall, M.
E.; Tucker, J . C.; Beecher, C. W. W.; Pezzuto, J . M.; Kinghorn, A. D.
J . Nat. Prod. 1996, 59, 290-292. (h) Kyogoku, K.; Hatakeyama, K.;
Yokomori, S.; Kawashima, M.; Aka, T. J pn. Tokkyo Koho 79 14105,
1979 (Chem. Abstr. 1979, 91, 157601y). (i) Kajima, H.; Chikamatsu,
Y.; Ando, H.; Kondo, M.; Naito, T. J pn. Kokai Tokkyo Koho J P 08
73364, 1996 (Chem. Abstr. 1996, 124, 325032j).
(2) For an excellent review on the chemistry of flavonoids, see: Seshadri,
T. R. Tetrahedron 1959, 6, 169-200.
(3) Nikaido, T.; Ohmoto, T.; Kinoshita, T.; Sankawa, U.; Monache, F.
D.; Botta, B.; Tomimori, T.; Miyaichi, Y.; Shirataki, Y.; Yokoe, I.;
Komatsu, M. Chem. Pharm. Bull. 1989, 37, 1392-1395.
(4) Trost, B. M.; Saulnier, M. G. Tetrahedron Lett. 1985, 26, 123-126.
(5) For the amended structure of sophoraflavanone A, see ref 6.
(6) Fukai, T.; Nomura, T. Heterocycles 1991, 32, 499-510.
(7) For acid-catalyzed prenylation, see: J ain, A. C.; Gupta, R. C.; Sarpal,
P. D. Tetrahedron 1978, 34, 3563-3567.
(8) Huang, C.-S.; Zhang, Z.; Li, Y.-L. J . Nat. Prod. 1998, 61, 1283-1285,
and references therein.
(9) Shirataki, Y.; Endo, M.; Yokoe, I.; Komatsu, M. Chem. Pharm. Bull.
1983, 31, 2859-2863.
(10) For revised structure, see: Shirataki, Y.; Yokoe, I.; Endo, M.;
Komatsu, M. Chem. Pharm. Bull. 1985, 33, 444-447.
(11) (a) Schu¨tz, B. A.; Wright, A. D.; Rali, T.; Sticher, O. Phytochemistry
1995, 40, 1273-1277. (b) Maurizio, B.; Giuseppe, S.; Liliana, L.;
Francesca, L. Heterocycles 1985, 23, 1147-1153.
(12) For spectral data of corresponding natural product, see: Stevens, J .
F.; Ivancic, M.; Hsu, V. L.; Deinzer, M. L. Phytochemistry 1997, 44,
1575-1585.
(13) For spectral data of corresponding natural product, see: Bohlmann,
F.; Hoffmann, E. Phytochemistry 1979, 18, 1371-1374.
(14) (a) J ohannes, R.; Margit, G.; Kalman, S.; Istvan, N. Arch. Pharm.
1976, 309, 151-152. (b) Alleluia, I. B. D.; Braz, R. F.; Gottlieb, O. R.;
Magalhaes, E. G.; Marques, R. Phytochemistry 1978, 17, 517-521.
(15) (a) Donnelly, D. M.; Philbin, E. M.; Wheeler, T. S. J . Chem. Soc. 1956,
4409-4411. (b) Philbin, E. M.; Swirski, J .; Wheeler, T. S. J . Chem.
Soc. 1956, 4455-4458. (c) Molho, D.; Gerphagnon, M.-C. Bull. Soc.
Chim. Fr. 1963, 607-610.
(16) For an earlier commentary article on the isomeric rearrangement of
the flavonoids, see: Mukerjee, S. K.; Seshadri, T. R. Chem. Ind.
(London) 1955, 271-275.
(17) Authentic samples of natural products are not available for direct
comparison.
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