First synthesis of (±)-C-3-prenylated flavanones

Article abstract of DOI:10.1081/SCC-120021998

2,4,6-tris(Methoxymethoxy)acetophenone (1) was first mono-alkylated with 3-methylbut-2-enyl bromide to yield 5-methyl-1-(2,4,6-trimethoxymethoxyphenyl)hex-4-en-1-one (2). The base catalyzed aldol condensation of 2 and substituted benzaldehydes gave chalco

Full text of DOI:10.1081/SCC-120021998

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First Synthesis of (±)-C-3-Prenylated Flavanones
Jin Xu a , Haishan Wang a & Mui Mui Sim a
a Medicinal and Combinatorial Chemistry Laboratory, Institute of Molecular and Cell Biology,
Singapore, Singapore
Published online: 17 Aug 2006.
To cite this article: Jin Xu , Haishan Wang & Mui Mui Sim (2003) First Synthesis of (±)-C-3-Prenylated Flavanones, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 33:15, 2737-2750, DOI:
10.1081/SCC-120021998
To link to this article: http://dx.doi.org/10.1081/SCC-120021998
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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 15, pp. 2737–2750, 2003
First Synthesis of (1)-C-3-Prenylated Flavanones
2
*
Jin Xu, Haishan Wang, and Mui Mui Sim
Medicinal and Combinatorial Chemistry Laboratory,
Institute of Molecular and Cell Biology,
Singapore, Singapore
ABSTRACT
2,4,6-tris(Methoxymethoxy)acetophenone (1) was first mono-alkyl-
ated with 3-methylbut-2-enyl bromide to yield 5-methyl-1-(2,4,6-tri-
methoxymethoxyphenyl)hex-4-en-1-one (2). The base catalyzed aldol
condensation of 2 and substituted benzaldehydes gave chalcones 3
in good yields. One pot cyclization and deprotection of the chalcones
were accomplished in refluxing 4 N HCl in MeOH to afford (ꢀ)-C-3-
prenylated flavanones.
Key Words: Prenylation; Chalcones; Flavanones.
*Correspondence: Mui Mui Sim, Medicinal Chemistry Laboratory,
MerLionpharmaceuticals Pte Ltd., 30 Medical Drive, Singapore 117609,
Singapore; Fax: þ65-67791117; E-mail: muimui@merlionpharma.com.
2737
DOI: 10.1081/SCC-120021998
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2738
Xu, Wang, and Sim
Flavonoids are naturally occurring compounds with important
biological activities.[1] It is thought that the prenyl groups (including
prenyl/isopentenyl, geranyl, and farnesyl side chains) in the flavonoids
and isoflavonoids play an important role in their biological activities by
increasing their lipophilicity and, consequently, enhancing their
antimicrobial activities through interaction with cellular membrane.[2–4]
Of the prenylated flavonoids, flavanone represents the most abundant
class with a rich variety of structures.[5] Majority of the natural prenyl-
ated flavanones are C-prenylated derivatives. C-prenylation by regio-
specific prenyltransferases is generated frequently at position 6/8 on
ring A and at position 30/50 on ring B, which are usually ortho to a
phenolic hydroxyl group with rich electrons,[6] and occasionally at C-3,
which is also somewhat electron rich due to conjugation. To the best of
our knowledge, C-3 prenylated flavanone has never been reported as
synthetic or natural product, though there indeed exists small amount
of naturally occurring C-3 prenylated flavones.[4,7]
The chemical syntheses of flavones and flavanones were generally
carried out by oxidative cyclization and cyclization of chalcones respec-
tively.[8,9] In the case of flavanol, the chalcones were epoxidized before
cyclizations were conducted.[10] Flavonols were synthesized either by
Algar–Flynn–Oyamada reaction[11] or by oxidation of flavone. Recently
Brouillard and coworkers reported a new synthetic route to flavonols
without using any oxidizing reagent.[12] The intermediate obtained via
Baker–Venkataraman rearrangement[13] was concomitantly cyclized and
dehydrated to yield the desired product. Of all the synthetic flavonoids
reported, only afew were C-prenylated at C-6 and/or C-8 on ring A.[14]
In view of the potential biological activities of C-3 prenylated flavanones,
we herein report the first synthesis of (2,3-cis)- and (2,3-trans)-C-3-
prenylated flavanones.
Alkylation of 2,4,6-tris(methoxymethoxy)acetophenone[10b] (1) with
3-methylbut-2-enyl bromide was carried out using different bases (Sch. 1).
The most optimized condition was achieved by treating 1 with LDA
in THF, as the desired mono-alkylated product 2 was obtained as the
major product. Other bases such as NaH[15] and tBuOK gave mainly
dialkylated products, whereas no reaction occurred when NaOEt was
employed.
The MOM protected 4-hexenophenone 2 and the MOM protected
hydroxybenzaldehydes or methoxybenzaldehydes were subjected to aldol
condensation with spontaneous elimination to give chalcones 3. Among
the several bases utilized, NaHMDS/THF afforded the best yield
(Table 1). Subsequent aldol condensations of 2 with various benzalde-
hydes were therefore carried out using NaHMDS in THF (Table 2).

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(1)-C-3-Prenylated Flavanones
2739
2
Scheme 1. Synthesis of C-3-prenylated flavanones (4a–f ).
Table 1. Isolated yields of 3a.
Isolated yields
of 3a (%)
Reagent
NaHMDS/THF
NaOH/EtOH
NaH/THF
36
22
12
8
LDA/THF
LiHMDS/THF
0
Since the benzaldehyde was readily reduced to benzyl alcohol as a result
of Cannizzaro reaction,[16] excess amounts of benzaldehydes (2 equiv.)
were added. The syntheses of chalcones 3c and 3e were also
repeated using the commonly employed NaOH/EtOH condition.
Although the yields of the chalcones obtained were comparable to
those obtained using NaHMDS/THF, the amount of benzyl alcohol
observed was significantly lower (decreased from 11 to 4%). We have
found that the yields of the chalcone 3 are comparable to the hindered a-
alkyl (iPr, c-pentyl) substituted chalcones yields reported in the Lit.[17]
Furthermore, it is correlated to the extent of substitution on the benzal-
dehyde. That is, condensation products (3a–c, 3e) from mono- and
di-substituted benzaldehydes afforded higher yields than those (3d, 3f )
from 2,4,5-trisubstituted benzaldehydes. Surprisingly, the yield of 3f is
lower than 3d even though the benzaldehyde is protected with the less

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2740
Xu, Wang, and Sim
Table 2. Isolated yields of chalcones 3 and flavanones 4.
Yields of 3 (%) Yields of
from 3 (%) from
Entry R1 R2 R3 R4 NaHMDS/THF NaOH/EtOH of 4 (%) 4-I:4-IIc
Yields
Ratio of
(a)
(b)
(c)
(d)
(e)
(f)
Xa H X
H
H
H
X
36
32
30
24
46
13
22
22
50
1:2
5:4
5:3
—
b
H
H
X
H
X X
H X
H X
—
42
55
No reaction
b
—
50
H OMe H
63
52
3:2
2:1
b
—
OMe H OMe OMe
aFor compounds 3(a–d), X ¼ OMOM; for 4(a–d), X ¼ OH.
bSynthesis was not carried out.
1
c(2,3)-cis to trans ratio of 4 as determined by H NMR.
Figure 1. NOE enchancement of 3c.
bulky methoxy group. The chalcones synthesized possess the expected
trans-E configurations as determined by 1D NOE experiments.[18] For
example, both H-100 and H-200 were enhanced when H-2 and H-6 of 3c
were irradiated, and similarly, both the CH2 and CH3 in 20,60-OMOM
groups were enhanced when H-b was irradiated (Fig. 1).
We envisage that final cyclization with simultaneous deprotection
of MOM should be achievable by refluxing chalcones 3 in acid.
Thus, instead of using the commonly employed bases such as
NaOAc (9a, 14a–b), NaOH[19] and piperidine,[19] 4 N HCl was used in

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(1)-C-3-Prenylated Flavanones
2741
2
the cyclization for chalcones 3. Using this approach, flavanones 4 were
isolated with more than 50% yield except for 4a and 4d. The progress of
1
3d ring closure reaction was monitored by TLC, MS and H NMR. The
intermediates were the partially deprotected chalcones. None of the
MOM protected or deprotected flavanone was observed. The reaction
gave rise to many unidentified polar mixtures upon further refluxing.
The difficulty in the ring closure reaction of chalcones 3a and 3d might
be caused by the sterically bulky 20-MOM in ring B. On the contrary,
chalcone 3f cyclized with ease to give flavanone 4f, most likely as a result
of the smaller 20-OMe group.
The final flavanones were obtained as mixtures of diastereomers
(2,3)-cis- and (2,3)-trans-4 (or 4-I and 4-II, respectively) with cis form
being the major products (except 4a) (Table 2). This is probably due to the
addition of hydrogen on the opposite direction of ring B during cycli-
1
zation. The relative configuration of 4 was determined by the H NMR
spectrum which showed that (2,3)-cis-4 possesses an axial/equatorial
coupling (J ¼ ꢁ3 Hz) while (2,3)-trans-4 possesses a diaxial coupling
(J ¼ 9–10 Hz) for H-2 and H-3.[20] The diastereomeric ratio of 4-I and
4-II were assigned according to the integration of H-2. Full assignment
(1H a nd13C) of 4-I and 4-II was accomplished with 2D-NMR experi-
ments (HMQC and HMBC).
We have successfully synthesized (ꢀ)-C-3-prenylated flavanones via
the a-prenylated chalcones. The ease of synthesis and the simultaneous
deprotection and cyclization of the chalcones in acid provide a conve-
nient route to the making of this class of compounds. Furthermore, the
C-3 prenyl group is a versatile handle for further functional groups
manipulation. Work is currently in progress to synthesize prenylated
flavanones with more diversity.
EXPERIMENTAL
THF was distilled from sodium benzophenone ketyl prior to use.
TLC was carried out on precoated plates: analytical (Merck Kieselgel
60 F254); preparative scale (Aldrich, silica, 1 mm). Column chromato-
graphy was performed on silica (Merck, 230–400 mesh). All the 1D
1
and 2D NMR experiments for H (400.13 MHz) and 13C (100.61 MHz)
were obtained on a Bruker AVANCE-400 digital NMR spectrometer.
1H a nd13C chemical shifts were expressed in ppm using their deuterated
solvents’ peak as internal standard (for CDCl3: 7.26 ppm (1H), 77.0 ppm
(13C); for acetone-d6: 2.05 ppm (1H), 29.5 ppm (13C)). FTIR spectrawere

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2742
Xu, Wang, and Sim
performed on a Bio-Rad Excalibur FT 3000 spectrometer. HRESI-MS
spectrawere taken on aPerSeptive Biosystems Mariner TOF spectrom-
eter at 70 eV. Elemental analyses were performed on Perkin Elmer 2400
CHN Elemental Analyzer.
Preparation of 5-methyl-1-(2,4,6-trimethoxymethoxyphenyl)hex-4-en-
1-one (2). To astirred solution of diisopropylamine (0.7 mL, 5 mmol) in
dry THF (10 mL) was added BuLi (3.1 mL, 5 mmol, 1.6 M in hexane) at
À75ꢂC. The solution was stirred for 15 min before adding 2,4,6-tris-
(methoxymethoxy)acetophenone (1) (600 mg, 2 mmol, in 5 mL THF).
The mixture was stirred for 30 min at 0ꢂC, and then 3-methylbut-2-
enyl bromide (461 ꢀL, 4 mmol) was added slowly. The reaction was
allowed to react at 4ꢂC for 20 h before it was quenched with ice and
saturated NaHCO3 (10 mL). The compound was extracted into EtOAc
(3 Â 20 mL), washed with brine (15 mL), and then water (15 mL), dried
with MgSO4 and concentrated. The residue was purified by flash column
chromatography (25% EtOAc in hexane) to give 2 (368mg, 50%, Rf 0.65)
as colorless oil. 1H NMR (CDCl3): ꢁ 6.49 (s, 2H, Ar), 5.13 (s, 2H,
OCH2O), 5.11 (t, 1H, J ¼ 7.2 Hz, H-4), 5.10 (s, 4H, 2 Â OCH2O), 3.46
(s, 3H, OCH3), 3.43 (s, 6H, 2 Â OCH3), 2.77 (t, 2H, J ¼ 7.2 Hz, H-2), 2.35
(q, 2H, J ¼ 7.2 Hz, H-3), 1.66, 1.61 (all s, 6H, 2 Â CH3). 13C NMR
(CDCl3): ꢁ 203.9, 159.2, 155.0 (2C), 132.1, 123.1, 116.5, 96.8 (2C), 94.6
(2C), 94.4, 56.2, 56.1 (2C), 44.9, 25.6, 22.4, 17.5. IR (KBr): 1698 cmÀ1
(C¼O). Anal. calcd. for C19H28O7: C, 61.94; H, 7.66. Found: C, 61.96; H,
7.33. HR-ESIMS: m/z [M þ H]þ calcd. for C19H29O7: 369.1913. Found:
369.1910.
Preparation of a-(300,300-dimethylallyl)-2,4,20,40,60-pentakis(methoxy-
methoxy)chalcone (3a). To astirred solution of 2 (120 mg, 0.33 mmol)
in dry THF (1.5 mL) was added NaHMDS (0.98 mL, 3 equiv., 1.0 M in
THF) at À75ꢂC. The solution was stirred for 30 min before adding 2,4-
bis(methoxymethoxy)benzaldehyde (147 mg, 0.65 mmol, 2 equiv.) in THF
(1 mL) at r.t. The mixture was refluxed for 30 h and then quenched with
ice and saturated NaHCO3, worked up as above. The residue was pur-
ified by flash column chromatography (30% EtOAc in hexane) to give 3a
1
(68.0 mg, 36%, Rf 0.24) as a yellow gum. H NMR (CDCl3): ꢁ 7.44 (s,
1H, H-b), 7.34 (d, 1H, J ¼ 8.6 Hz, H-6), 6.72 (d, 1H, J ¼ 2.3 Hz, H-3),
6.69 (dd, 1H, J ¼ 8.6, 2.3 Hz, H-5), 6.52 (s, 2H, H-30, H-50), 5.21 (br t, 1H,
J ¼ 3.5 Hz, H-200), 5.16, 5.15, 5.08, 5.05 (all s, 10H, 5 Â OCH2O), 3.47,
3.46, 3.38, 3.31 (all s, 15H, 5 Â OCH3), 3.33 (br d, 2H, J ¼ 3.5 Hz, H-100),
1.72, 1.67 (all s, 6H, 2 Â CH3). 13C NMR (CDCl3): ꢁ 196.9, 159.1, 158.9,
156.3, 155.5 (2C), 141.2, 137.6, 132.0, 130.9, 122.5, 119.7, 115.1, 108.8,
103.4, 97.0 (2C), 94.9, 94.6, 94.5 (2C), 94.3, 56.2 (3C), 56.1 (2C), 25.84,
25.79, 18.0. IR (KBr): 1649 cmÀ1 (C¼C-C¼O). Anal. calcd. for

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(1)-C-3-Prenylated Flavanones
2743
2
C30H40O11: C, 62.49; H, 6.99. Found: C, 62.44; H, 7.40. HR-ESIMS: m/z
[M þ H]þ calcd. for C30H41O11. 577.2649. Found: 577.2652.
a-(300,300-Dimethylallyl)-3,4,20,40,60 -pentakis(methoxymethoxy)chal-
cone (3b). Prepared as 3a from 2 (90 mg, 0.24 mmol) and 3,4-bis(methoxy-
methoxy)benzaldehyde (111 mg, 0.49 mmol). Column chromatography
(30% EtOAc in hexane) gave 3b (45.5 mg, 32%, Rf 0.24) as a yellow
1
gum. H NMR (CDCl3): ꢁ 7.19 (s, 1H, H-b), 7.17 (d, 1H, J ¼ 2.0 Hz,
H-1), 7.12 (d, 1H, J ¼ 8.0 Hz, H-5), 7.01 (dd, 1H, J ¼ 8.0, 2.0 Hz, H-6),
6.52 (s, 2H, H-30, H-50), 5.25, 5.19, 5.17, 5.09 (all s, 10H, 5 Â OCH2O),
5.08 (hidden, 1H, H-200), 3.50, 3.49, 3.48, 3.37 (all s, 15H, 5 Â OCH3), 3.46
(d, 2H, J ¼ 3.4 Hz, H-100), 1.72, 1.70 (all s, 6H, 2 Â CH3). 13C NMR
(CDCl3): ꢁ 196.7, 159.3, 155.5, 147.8, 146.8, 142.0, 141.7, 132.7, 130.2,
124.6, 122.1, 118.3, 116.0, 114.7, 96.9, 95.4, 95.1, 94.6, 94.4, 56.3, 56.2,
25.7, 25.5, 18.1. IR (KBr): 1649 cmÀ1 (C¼C-C¼O). HR-ESIMS: m/z
[M þ H]þ calcd. for C30H41O11: 577.2649. Found: 577.2641.
a-(300,300-Dimethylallyl)-4,20,40,60-tetrakis(methoxymethoxy)chalcone
(3c). Prepared as 3a from 2 (250 mg, 0.68 mmol) and 4-methoxymethoxy-
benzaldehyde (225 mg, 1.36 mmol). Column chromatography (25%
EtOAc in hexane) gave 3c (105.2 mg, 30%, Rf 0.34) as a pale yellow
gum. 1H NMR (CDCl3): ꢁ 7.31 (dd, 2H, J ¼ 8.8, 2.0 Hz, H-2, H-6),
7.22 (s, 1H, H-b), 7.00 (dd, 2H, J ¼ 8.8, 2.0 Hz, H-3, H-5), 6.52 (s, 2H,
H-30, H-50), 5.18 (hidden, 1H, H-200), 5.19, 5.17, 5.09 (all s,
8H, 4 Â OCH2O), 3.50, 3.47, 3.37 (all s, 12H, 4 Â OCH3), 3.38 (d, 2H,
J ¼ 3.2 Hz, H-100), 1.73, 1.72 (all s, 6H, 2 Â CH3). 13C NMR (CDCl3): ꢁ
196.8, 159.2, 157.6, 155.5 (2C), 142.1, 141.2, 132.5, 131.3 (2C), 129.5,
122.1, 116.0 (2C), 114.7, 96.9 (2C), 94.6, 94.4 (2C), 94.2, 56.3, 56.2
(2C), 56.1, 25.8, 25.5, 18.0. IR (KBr): 1650 cmÀ1 (C¼C-C¼O). Anal.
calcd. for C28H36O9: C, 65.10; H, 7.02. Found: C, 64.82; H, 7.35. HR-
ESIMS: m/z [M þ H]þ calcd. for C28H37O9, 517.2438. Found: 517.2432.
a-(300,300-Dimethylallyl)-2,4,5,20,40,60-hexakis(methoxymethoxy)chal-
cone (3d). Prepared as 3a from 2 (137 mg, 0.37 mmol) and 2,4,5-
tris-(methoxymethoxy)benzaldehyde (213 mg, 0.74 mmol). Column
chromatography (30% EtOAc in hexane) gave 3d (56.8 mg, 24%, Rf
1
0.16) as a brown yellow gum. H NMR (CDCl3): ꢁ 7.41 (s, 1H, H-b),
7.24 (s, 1H, H-6), 6.90 (s, 1H, H-3), 6.51 (s, 2H, H-30, H-50), 5.21, 5.14,
5.09, 5.08, 4.99 (all s, 12H, 6 Â OCH2O), 5.19 (hidden, 1H, H-200), 3.49,
3.474, 3.470, 3.38, 3.29 (all s, 18H, 6 Â OCH3), 3.33 (d, 2H, J ¼ 3.2 Hz, H-
100), 1.71, 1.66 (all s, 6H, 2 Â CH3). 13C NMR (CDCl3): ꢁ 196.8, 159.1,
155.6, 151.2, 149.1, 141.6, 141.4, 137.4, 132.5, 122.4, 119.9, 119.5, 114.9,
104.8, 97.0, 96.2, 95.7, 95.3, 94.5, 56.3, 56.1, 25.7, 25.6, 18.0. IR (KBr):
1651 cmÀ1 (C¼C-C¼O). HR-ESIMS: m/z [M þ H]þ calcd. for
C32H45O13: 637.2860. Found: 637.2873.

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2744
Xu, Wang, and Sim
a-(300,300-Dimethylallyl)-4-methoxy-20,40,60-tris(methoxymethoxy)chal-
cone (3e). Prepared as 3a from 2 (50 mg, 0.14 mmol) and 4-methoxyben-
zaldehyde (33 mL, 0.27 mmol). Column chromatography (25% EtOAc in
hexane) gave 3e (30.7 mg, 46%, Rf 0.42) as a pale yellow gum. H NMR
1
(CDCl3): ꢁ 7.33 (dd, 2H, J ¼ 8.6, 1.7 Hz, H-2, H-6), 7.22 (s, 1H, H-b), 6.87
(dd, 2H, J ¼ 8.6, 1.7 Hz, H-3, H-5), 6.52 (s, 2H, H-30, H-50), 5.18 (t, 1H,
J ¼ 4.0 Hz, H-200), 5.17, 5.09 (all s, 6H, 3 Â OCH2O), 3.82, 3.50, 3.37 (all s,
12H, 4 Â OCH3), 3.40 (d, 2H, J ¼ 4.0 Hz, H-100), 1.74, 1.73 (all s, 6H,
2 Â CH3). 13C NMR (CDCl3): ꢁ 196.7, 160.0, 159.2, 155.4 (2C), 142.4,
140.8, 132.5, 131.5 (2C), 128.4, 122.1, 114.8, 113.9 (2C), 96.9 (2C),
94.6, 94.3 (2C), 56.24, 56.18 (2C), 55.3, 25.8, 25.5, 18.1. IR (KBr):
1649 cmÀ1 (C¼C-C¼O). HR-ESIMS: m/z [M þ H]þ calcd. for
C27H35O8. 487.2332. Found: 487.2346.
a-(300,300-Dimethylallyl)-2,4,5-trimethoxy-20,40,60-tris(methoxymethoxy)-
chalcone (3f). Prepared as 3a from 2 (250mg, 0.68mmol) and 2,4,5-tri-
methoxybenzaldehyde (266mg, 1.36mmol). Column chromatography
(30% EtOAc in hexane) gave 3f (50.0 mg, 13%, Rf 0.25) as a yellow
1
gum. H NMR (CDCl3): ꢁ 7.48 (s, 1H, H-b), 7.05 (s, 1H, H-6), 6.54
(s, 2H, H-30, H-50), 6.45 (s, 1H, H-3), 5.23 (br t, 1H, J ¼ 4.1 Hz, H-200),
5.17, 5.10 (all s, 6H, 3Â OCH2O), 3.89, 3.77, 3.71 (all s, 9H, 3Â OCH3),
3.49, 3.40 (all s, 9H, 3Â OCH3), 3.35 (d, 2H, J ¼ 4.1 Hz, H-100), 1.73,
1.68 (all s, 6H, 2Â CH3). 13C NMR (CDCl3):
ꢁ 196.8, 159.1,
155.5 (2C), 152.7, 150.6, 142.6, 140.5, 138.4, 132.6, 123.3, 116.4,
115.0, 113.6, 97.0 (2C), 96.6, 94.6, 94.5 (2C), 56.3, 56.2 (2C), 56.1 (2C), 56.0,
25.8, 25.7, 18.3. IR (KBr): 1656cmÀ1 (C¼C-C¼O). HR-ESIMS: m/z
[M þ H]þ calcd. for C29H39O10: 547.2543. Found: 547.2538.
General Procedure for the Preparation of Flavanones 4
Chalcones 3 were treated with 4 N HCl in refluxing MeOH for
8–15 h. After concentration, the mixture was extracted into EtOAc,
washed with brine and water, and then concentrated again. The residue
was purified by preparative TLC to afford 4.
(2,3)-cis and (2,3)-trans-3-(300,300-Dimethylallyl)-5,7,20,40-tetrahydroxy-
flavanone (4a). 4a, prepared from 3a (18.5 mg, 0.032 mmol), was obtained
as a yellow solid (2.5 mg, 22%, Rf 0.17, 5% MeOH in CHCl3). IR (KBr):
3672 (OH), 3560-3300 (OH, br), 1637 (C¼O) cmÀ1. HR-ESIMS: m/z
[M þ H]þ calcd. for C20H21O6: 357.1338. Found: 357.1341.
(2,3)-cis-3-(300,300-Dimethylallyl)-5,7,20,40-tetrahydroxyflavanone (4a-I)
1H NMR (acetone-d6): ꢁ 12.21 (s, 1H, OH-5), 7.36 (d, 1H, J ¼ 8.8 Hz,

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(1)-C-3-Prenylated Flavanones
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H-60), 6.48 (d, 1H, J ¼ 2.2 Hz, H-30, overlap with H-30 of 4a–II), 6.46
(dd, 1H, J ¼ 8.8, 2.2 Hz, H-50), 6.05 (d, 1H, J ¼ 1.9 Hz, H-8), 5.97
(d, 1H, J ¼ 1.9 Hz, H-6), 5.75 (d, 1H, J ¼ 3.2 Hz, H-2), 5.00 (t, 1H,
J ¼ 6.6 Hz, H-200), 2.82–2.87 (m, 1H, H-3), 2.13–2.18 (m, 2H, H-100),
1.53, 1.32 (all s, 6H, 2 Â CH3). 13C NMR (acetone-d6): ꢁ 200.7, 167.2,
165.0, 164.4, 158.8, 155.5, 133.2, 128.5, 121.3, 116.0, 107.1, 103.1, 96.7,
95.4, 77.7, 49.3, 25.5, 25.1, 17.3.
(2,3)-trans-3-(300,300-Dimethylallyl)-5,7, 20,40-tetrahydroxyflavanone (4a-II).
1H NMR (acetone-d6): ꢁ 12.34 (s, 1H, OH-5), 7.19 (d, 1H, J ¼ 8.5 Hz, H-
60), 6.48 (d, 1H, J ¼ 2.2 Hz, H-30, overlap with H-30 of 4a-I), 6.40 (dd, 1H,
J ¼ 8.5, 2.2 Hz, H-50), 5.93 (d, 1H, J ¼ 2.2 Hz, H-6), 5.89 (d, 1H,
J ¼ 2.2 Hz, H-8), 5.56 (d, 1H, J ¼ 11.0 Hz, H-2), 5.10 (t, 1H, J ¼ 6.9 Hz,
H-200), 3.30–3.35 (m, 1H, H-3), 2.45–2.52 (m, 1H, H-100), 2.18–2.26 (m,
1H, H-100), 1.59, 1.39 (all s, 6H, 2 Â CH3). 13C NMR (acetone-d6): ꢁ 199.4,
167.2, 165.0, 164.1, 159.4, 157.2, 133.4, 130.2, 121.3, 115.9, 107.5, 103.3,
96.3, 95.2, 78.1, 49.3, 25.6, 25.1, 17.3.
(2,3)-cis- and (2,3)-trans-3-(300,300-Dimethylallyl)-5,7,30,40-tetrahydroxy-
flavanone (4b). 4b, prepared from 3b (45.5 mg, 0.079 mmol), was obtained
as a yellowish brown solid (14.0 mg, 50%, Rf 0.26, 5% MeOH in CHCl3). IR
(KBr): 3670 (OH), 3560-3190 (OH, br), 1640 (C¼O) cmÀ1. HR-ESIMS: m/z
[M þ H]þ calcd. for C20H21O6: 357.1338. Found, 357.1143.
(2,3)-cis-3-(300,300-Dimethylallyl)-5,7,30,40-tetrahydroxyflavanone
(4b-I)
1H NMR (acetone-d6): ꢁ 12.18 (s, 1H, OH-5), 7.00 (d, 1H, J ¼ 2.0 Hz,
H-20), 6.88 (d, 1H, J ¼ 8.0 Hz, H-50), 6.85 (overlap, 1H, H-60), 6.04 (d,
1H, J ¼ 2.1 Hz, H-8), 5.97 (d, 1H, J ¼ 2.1 Hz, H-6), 5.58 (d, 1H,
J ¼ 3.1 Hz, H-2), 5.02 (t, 1H, J ¼ 7.2 Hz, H-200), 2.68–2.72 (m, 1H, H-3),
2.15–2.21 (m, 2H, H-100), 1.55, 1.31 (all s, 6H, 2 Â CH3). 13C NMR (acet-
one-d6): ꢁ 200.0, 166.9, 165.1, 163.3, 145.7, 145.4, 133.8, 129.4, 121.0,
118.1, 115.7, 113.8, 101.9, 96.6, 95.3, 81.2, 51.4, 25.5, 24.0, 17.2.
(2,3)-trans-3-(300,300-Dimethylallyl)-5,7, 30,40-tetrahydroxyflavanone (4b–II).
1H NMR (acetone-d6): ꢁ 12.28 (s, 1H, OH-5), 6.97 (d, 1H, J ¼ 2.0 Hz, H-
20), 6.86 (overlap, 1H, H-50), 6.81 (dd, 1H, J ¼ 8.0, 2.0 Hz, H-60), 5.93 (d,
1H, J ¼ 2.2 Hz, H-6), 5.91 (d, 1H, J ¼ 2.2 Hz, H-8), 5.16 (d, 1H,
J ¼ 10.3 Hz, H-2), 5.10 (t, 1H, J ¼ 7.2 Hz, H-200), 3.12 (dt, 1H, J ¼ 10.3,
5.1 Hz, H-3), 2.48–2.55 (m, 1H, H-100), 2.09–2.15 (m, 1H, H-100), 1.62,
1.40 (all s, 6H, 2 Â CH3). 13C NMR (acetone-d6): ꢁ 198.4, 167.1, 165.0,
163.3, 146.1, 145.7, 133.4, 130.2, 121.0, 120.1, 115.6, 115.3, 102.7, 96.4,
95.3, 82.9, 50.2, 25.6, 25.1, 17.5.
(2,3)-cis- and (2,3)-trans-3-(300,300-Dimethylallyl)-5,7,40-trihydroxy-
flavanone (4c). 4c, prepared from 3c (32.0 mg, 0.062 mmol), was
obtained as a yellowish brown solid (11.7 mg, 55%, Rf 0.18, 3%
MeOH in CHCl3). IR (KBr): 3670 (OH), 3540–3197 (OH, br), 1640

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2746
Xu, Wang, and Sim
(C¼O) cmÀ1. HR-ESIMS: m/z [M þ H]þ calcd. for C20H21O5: 341.1389.
Found: 341.1394.
(2,3)-cis-3-(300,300-Dimethylallyl)-5,7,40-trihydroxyflavanone
(4c-I).
1H NMR (acetone-d6): ꢁ 12.16 (s, 1H, OH-5), 7.33 (d, 2H, J ¼ 8.8 Hz,
H-20, H-60), 6.90 (d, 2H, J ¼ 8.8 Hz, H-30, H-50), 6.03 (d, 1H,
J ¼ 2.1 Hz, H-8), 5.95 (d, 1H, J ¼ 2.1 Hz, H-6), 5.61 (d, 1H, J ¼ 3.0 Hz,
H-2), 4.99 (br t, 1H, J ¼ 7.5 Hz, H-200), 2.66–2.71 (m, 1H, H-3), 2.12–2.22
(m, 2H, H-100), 1.53, 1.28 (all s, 6H, 2 Â CH3). 13C NMR (acetone-d6): ꢁ
200.2, 167.1, 165.1, 163.2, 157.8, 133.4, 128.4, 127.7 (2C), 120.9, 115.7
(2C), 101.8, 96.6, 95.3, 81.2, 51.4, 25.4, 23.9, 17.1.
(2,3)-trans-3-(300,300-Dimethylallyl)-5,7,40-trihydroxyflavanone (4c-II).
1H NMR (acetone-d6): ꢁ 12.27 (s, 1H, OH-5), 7.30 (d, 2H, J ¼ 8.8 Hz,
H-20, H-60), 6.87 (d, 2H, J ¼ 8.8 Hz, H-30, H-50), 5.92 (d, 1H,
J ¼ 2.1 Hz, H-6), 5.88 (d, 1H, J ¼ 2.1 Hz, H-8), 5.20 (d, 1H, J ¼ 9.9 Hz,
H-2), 5.06 (br t, 1H, J ¼ 7.5 Hz, H-200), 3.12–3.18 (m, 1H, H-3, hidden),
2.47–2.53 (m, 1H, H-100), 2.12–2.18 (m, 1H, H-100), 1.60, 1.35 (all s, 6H,
2 Â CH3). 13C NMR (acetone-d6): ꢁ 199.9, 167.3, 164.9, 163.3, 158.5,
133.7, 129.7 (2C), 129.2, 120.8, 115.6 (2C), 102.7, 96.4, 95.3, 82.8, 49.9,
25.5, 24.8, 17.4.
(2,3)-cis- and (2,3)-trans-3-(300,300-Dimethylallyl)-5,7-dihydroxy-40-methoxy-
flavanone (4e). 4e, prepared from 3e (30.7 mg, 0.063 mmol), was obtained as
ayellow gum (14.0 mg, 63%, Rf 0.46, 25% EtOAc in hexane). IR (KBr): 3632
(OH), 3500-3200 (OH, br), 1639 (C¼O) cmÀ1. HR-ESIMS: m/z [M þ H]þ
calcd. for C21H23O5: 355.1546. Found: 355.1549.
(2,3)-cis-3-(300,300-Dimethylallyl)-5,7-dihydroxy-40-methoxyflavanone
1
(4e-I). H NMR (CDCl3): ꢁ 12.07 (s, 1H, OH-5), 7.33 (d, 2H, J ¼ 8.8 Hz,
H-20, H-60), 6.94 (d, 2H, J ¼ 8.8 Hz, H-30, H-50), 6.03 (d, 1H, J ¼ 1.9 Hz,
H-8), 6.01 (d, 1H, J ¼ 1.9 Hz, H-6), 5.52 (d, 1H, J ¼ 2.9 Hz, H-2), 4.96 (br
t, 1H, J ¼ 7.4 Hz, H-200), 3.83 (s, 3H, OCH3), 2.64 (ddd, 1H, J ¼ 8.8, 5.7,
3.1 Hz, H-3), 2.20–2.25 (m, 1H, H-100), 2.10–2.19 (m, 1H, H-100), 1.57,
1.30 (all s, 6H, 2 Â CH3). 13C NMR (CDCl3): ꢁ 199.7, 164.8, 164.4, 162.6,
159.3, 134.2, 128.8, 127.0 (2C), 119.6, 113.9 (2C), 102.0, 96.7, 95.3, 80.7,
55.3, 51.2, 25.6, 23.5, 17.4.
(2,3)-trans-3-(300,300-Dimethylallyl)-5,7-dihydroxy-40-methoxyflavanone
(4e-II). lH NMR (CDCl3): ꢁ 12.24 (s, 1H, OH-5), 7.29 (d, 2H, J ¼ 8.7 Hz,
H-20, H-60), 6.91 (d, 2H, J ¼ 8.7 Hz, H-30, H-50), 5.97 (d, 1H, J ¼ 2.0 Hz,
H-6), 5.92 (d, 1H, J ¼ 2.0 Hz, H-8), 5.21 (d, 1H, J ¼ 9.7 Hz, H-2), 5.03 (br
t, 1H, J ¼ 7.3 Hz, H-200), 3.82 (s, 3H, OCH3), 3.04 (dt, 1H, J ¼ 9.7, 5.3 Hz,
H-3), 2.52–2.60 (m, 1H, H-100), 2.10–2.18 (m, 1H, H-100), 1.65, 1.39 (all s,
6H, 2 Â CH3). 13C NMR (CDCl3): ꢁ 198.0, 164.9, 164.3, 162.4, 159.9,
134.5, 129.7, 128.8 (2C), 119.7, 114.0 (2C), 102.9, 96.5, 95.2, 81.9, 55.3,
49.8, 25.8, 24.9, 17.8.

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(1)-C-3-Prenylated Flavanones
2747
2
(2,3)-cis- and (2,3)-trans-3-(300,300-Dimethylallyl)-5,7-dihydroxy-20,40,50-
trimethoxyflavanone (4f). 4f, prepa red from3f (50.0 mg, 0.092 mmol), was
obtained as a yellow solid (19.7 mg, 52%, Rf 0.26, 10% MeOH in CHCl3).
IR (KBr): 3676 (OH), 3560–3190 (OH, br), 1640 (C¼O) cmÀ1. HR-
ESIMS: m/z [M þ H]þ calcd. for C23H27O7: 415.1757. Found: 415.1741.
(2,3)-cis-3-(300,300-Dimethylallyl)-5,7-dihydroxy-20,40,50-trimethoxy-
l
flavanone (4f-I). H NMR (acetone-d6): ꢁ 12.20 (s, 1H, OH-5), 7.23
(s, 1H, H-60), 6.79 (s, 1H, H-30), 6.06 (d, 1H, J ¼ 2.2 Hz, H-8), 5.98
(d, 1H, J ¼ 2.2 Hz, H-6), 5.75 (d, 1H, J ¼ 2.9 Hz, H-2), 4.93 (br t, 1H,
J ¼ 7.0 Hz, H-200), 3.86, 3.85 (hidden), 3.81 (all s, 9H, 3 Â OCH3),
2.50–2.55 (m, 1H, H-3), 2.15–2.19 (m, 2H, H-100, overlap with
H-100of 4f-II), 1.52, 1.30 (all s, 6H, 2 Â CH3). 13C NMR (acetone-d6):
ꢁ 200.3, 166.8, 165.2, 163.4, 150.8 (2C), 143.8, 133.2, 121.1, 116.9,
113.2, 101.7, 98.4, 96.7, 95.4, 77.3, 57.1, 56.2, 56.1, 50.7, 25.4, 24.5, 17.1.
(2,3)-trans-3-(300,300-Dimethylallyl)-5,7-dihydroxy-20,40,50-trimethoxy-
flavanone (4f-II). 1H NMR (acetone-d6): ꢁ 12.33 (s, 1H, OH-5), 7.11
(s, 1H, H-60), 6.77 (s, 1H, H-30), 5.94 (d, 1H, J ¼ 2.2 Hz, H-8), 5.89 (d,
1H, J ¼ 2.2 Hz, H-6), 5.60 (d, 1H, J ¼ 11.5 Hz, H-2), 5.03 (br t, 1H,
J ¼ 7.0 Hz, H-200), 3.87, 3.84, 3.76 (all s, 9H, 3 Â OCH3), 2.75–2.80 (m,
00
1H, H-3), 2.15–2.19 (m, 2H, H-100, overla p with H-1 of 4f-I), 1.57, 1.32
(all s, 6H, 2 Â CH3). 13C NMR (acetone-d6): ꢁ 199.2, 167.0, 165.0, 164.0,
152.9, 151.5, 144.0, 137.0, 121.3, 117.2, 113.8, 102.6, 98.5, 96.3, 95.1,
77.5, 56.7, 56.4, 56.0, 49.3, 25.6, 24.5, 17.2.
ACKNOWLEDGMENT
This work was supported by Agency for Science, Technology, and
Research of Singapore.
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