The absolute configuration of 1-(3′,4′-dihydroxycinnamoyl) cyclopentane-2,3-diol from the Amazonian tree Chimarrhis turbinata

Article abstract of DOI:10.1021/np050522y

An antioxidant, 1-(3′,4′-dihydroxycinnamoyl)cyclopentane-2,3- diol [or (E)-2,3-dihydroxycyclopentyl-3-(3′,4′-dihydroxyphenyl) acrylate (1)], and two known trans- and cis-chlorogenic acid methyl esters were isolated from the ethanolic extract of the leaves

Full text of DOI:10.1021/np050522y

1046
J. Nat. Prod. 2006, 69, 1046-1050
The Absolute Configuration of 1-(3′,4′-Dihydroxycinnamoyl)cyclopentane-2,3-diol from the
Amazonian Tree Chimarrhis turbinata
Carmen Lucia Cardoso,† Vanderlan da Silva Bolzani,*,† Dulce Helena Siqueira Silva,† Hideki Ishii,‡ Nina Berova,‡ and
Koji Nakanishi‡
NuBBE, Nu´cleo de Bioss´ıntese, Bioensaios e Ecofisologia de Produtos Naturais, Instituto de Qu´ımica, UniVersidade Estadual Paulista
(UNESP), C.P. 355, 14800-900, Araraquara-SP, Brazil, and Department of Chemistry, Columbia UniVersity, New York, New York 10027
ReceiVed December 12, 2005
An antioxidant, 1-(3′,4′-dihydroxycinnamoyl)cyclopentane-2,3-diol [or (E)-2,3-dihydroxycyclopentyl-3-(3′,4′-dihydrox-
yphenyl)acrylate (1)], and two known trans- and cis-chlorogenic acid methyl esters were isolated from the ethanolic
extract of the leaves of Chimarrhis turbinata. The relative configuration of 1 was determined by NMR and by comparison
of the circular dichroic spectrum (CD) with those of the enantiomers of synthetic 3′,4′-dimethoxycinnamoyl analogues.
The absolute configuration of one of the synthetic enantiomers was determined using the CD exciton chirality method.
This established the structure of naturally occurring 1 as (E)-2,3-dihydroxycyclopentyl-3-(3′,4′-dihydroxyphenyl)acrylate.
The tree Chimarrhis turbinata DC. Prodr. (Rubiaceae), which
grows mainly in Central America, tropical South America, and the
Caribbean Islands, is prized for its light and resistant wood, which
is used in the manufacture of tools. In the Amazonian region, the
species is constantly under threat from the indigenous population,
who construct paddles from the wood, giving rise to the popular
name of “pau-de-remo” for the species.1 Previous phytochemical
studies of C. turbinata established the presence of indole alkaloids,
including turbinatine, which was identified as a key intermediate
in the biosynthesis of corinantheans.2 Further investigations have
led to the isolation of several phenolics with antioxidant proper-
ties,3,4 including the chlorogenic acid derivative 1-(3′,4′-dihydroxy-
cinnamoyl)cyclopentane-2,3-diol (1)5 and trans- and cis-chlorogenic
acid methyl esters (2 and 3, respectively). Identification of the
known compounds 2 and 3 was based on their spectroscopic data
and comparison with literature values. While compound 1 had been
reported previously from Prunus cerasus, its relative and absolute
configurations were not determined.6
We here report the structural elucidation and determination of
the absolute configuration of 1 by application of the circular dichroic
(CD) exciton chirality technique. In this nonempirical microscale
method for establishing the conformation and absolute configuration
of chiral molecules in solution,7-11 the hydroxyl groups are
converted into corresponding esters with p-substituted benzoates
or other chromophores.8 Interactions between the electric transition
moments of proximally located chirally disposed chromophores give
rise to CD curves that exhibit split Cotton effects or couplets,
although the cisoid triol structure 1 exhibited a weak but distinct
CD spectrum,6 as presented in Figure 3. To obtain a dichromophoric
compound, attempts were made to derivatize 1 directly, but were
unsuccessful owing to the instability of the molecule under acidic
and basic conditions. The absolute configuration of 1 was thus
established from the CD spectra of synthetic enantiomers of 1-(3′,4′-
dimethoxycinnamoyl)cyclopentane-2,3-diol (4). The absolute con-
figuration of one of these synthetic enantiomers was then determined
by the CD exciton chirality method.
243 (3.76), 299 (3.81), 327 (3.90) nm; IR (KBr) νmax 3414 (OH),
1694 (CdO) cm-1; 1H and 13C NMR data see Table 1; EIMS m/z
281 (10), [M + H]+ 180 (20), 163 (82).
The molecular formula of 1, as determined from ESIMS and
13C NMR data, was C14H16O6. Signals at δ 149.5, 147.2, 127.6,
122.9, 115.2, and 116.5 in the 13C NMR of 1 (Table 1) were typical
of a 3′,4′-dihydroxylcinnamoyl group, while those at δ 146.8 and
115.3, together with correlations indicated by the gHMBC spectrum
between H-7′ and H-8′ with the carbonyl group at 168.7, suggested
the presence of a caffeic acid moiety. The signals at δ 72.0 (s),
73.6, and 71.5 were assigned to the hydroxymethine carbons C-1,
C-2, and C-3. When the spectroscopic data of 1 were compared
with those of chlorogenic acid, the presence of methylene carbon
signals at δ 38.2 and 38.9, and the absence of a quaternary carbon
around δ 70.0 and a second carbonyl group, suggested that the
caffeic acid moiety was not connected to quinic acid but to a
cyclopentane-2,3-diol moiety.
The 1H NMR of 1 (Table 1) revealed two aromatic protons
appearing as doublets at δ 7.46 (J ) 16.0 Hz, H-7′) and 6.16 (J )
16.0 Hz, H-8′), the coupling constant of which suggested that they
were trans-oriented. The signals at δ 6.85 (J ) 2.0; 8.0 Hz), 6.68
(J ) 8.0 Hz), and 6.95 (J ) 2.0 Hz) were assigned to the aromatic
hydrogens of a 3′,4′-dihydroxylcinnamoyl group and exhibited
chemical shifts similar to those of the corresponding protons in
chlorogenic acid.12 The presence of a caffeic acid moiety in 1 was
confirmed from peaks at m/z 180 and 163 in the EIMS. The multiple
signals at δ 5.23 (H-1) and 4.07 (H-3) together with the doublet of
doublets at δ 3.62 (H-2) were attributed to three hydroxymethine
hydrogens, while, on the basis of 1D correlation from the NOESY
and COSY spectra, those at δ 1.98, 2.07 (H-4), 2.12 and 1.93 (H-
5) could be assigned to the four protons of two methylene groups
that completed a pentacyclic system. Individual irradiation of each
hydrogen of the ring system permitted the observation of visible
spatial correlations between H-1, H-2, and H-5, between H-2, H-1,
and H-3, and between H-3, H-2, and H-4. On the basis of these
correlations it was established that the oxymethine hydrogens were
in the same plane. Moreover, the coupling constants of H-2 (J )
3.0; 3.0 Hz) suggested cis coupling between H-2, H-1, and H-7,
and from the evidence thus available the relative configuration of
1 could be inferred (Figure 1).
Results and Discussion
Compound 1, 1-(3′,4′-dihydroxycinnamoyl)cyclopentane-2,3-diol,
was isolated from an EtOH extract of the leaves of C. turbinata as
a brown powder; UV (MeOH) λmax (log ꢀ) 205 (3.95), 215 (3.94),
Comparison of the spectroscopic data of 1 with literature values6
revealed that compound 1 was an enantiomer of the compound
previously described as 1-(3′,4′-dihydroxycinnamoyl)cyclopentane-
2,3-diol. The absolute configuration of 1 could not be determined
in a straightforward manner, since in addition to the flexibility of
* To whom correspondence should be addressed. Tel: 55(16)33016660.
Fax: 55(16)33227932. E-mail: bolzaniv@iq.unesp.br.
† Universidade Estadual Paulista.
‡ Columbia University.
10.1021/np050522y CCC: $33.50
© 2006 American Chemical Society and American Society of Pharmacognosy
Published on Web 06/13/2006

Absolute Configuration of a Compound from Chimarrhis turbinata
Journal of Natural Products, 2006, Vol. 69, No. 7 1047
Figure 1. Structures of compounds 1-3.
Figure 2. (A) Resolution of enantiomers 4 by Chiralcel OD
column. Experimental conditions: eluent hexane/2-propanol (3:1),
flow 1.0 mL min-1, λ ) 254 nm. (B) Resolution of enantiomers 8
by Chiralcel OD column. Experimental conditions: eluted with
hexane/2-propanol (3:1), flow 1.0 mL min-1, λ ) 254 nm.
the cyclopentane-1,2,3-triol system, the CD of 1 exhibited no
conspicuous extreme (Figure 3). Hence application of the CD
exciton chirality method10,11 was carried out.
The racemic analogues 4 were prepared by reacting syn-
cyclopentane-1,2,3-triol (5)9 with 1-(3′,4′-dimethoxycinnamoyl)-
1,2,4-triazole (6) (Scheme 1) and resolved by chiral HPLC using a
Chiralcel OD column and isocratic elution with hexane/2-propanol
(3:1) (Figure 2). As shown in Figure 2, enantiomers 4a and 4b and
the isomer 7 showed baseline separation under these conditions.
When enantiomer 4b was maintained in solution in the HPLC
mobile phase for 12 h, 10% of enantiomer 4a was generated (80%
ee) possibly through two consecutive 1,2-migrations.
The CD spectra of enantiomers 4a and 4b were weak but distinct
(Figure 3), with that of 4b being very similar to the spectrum
exhibited by the natural product 1. The absolute configuration of
enantiomer 4b was therefore determined using the CD exciton
chirality method.
To restrict the flexibility of the cyclopentane ring as well as to
introduce a second chromophore that might couple with the
1-aromatic chromophore, the hydroxyl groups were converted into
acetals by reaction with 4-biphenylcarboaldehyde in the presence
of a catalytic amount of p-toluenesulfonic acid (p-TsOH) (Scheme
2). After stirring the reaction mixture for 10 h, substrate 4b was
completely consumed, giving rise to the racemic endo compounds
8 (60% yield) and the corresponding racemic exo isomer (15%
yield). Interestingly, the 4-biphenyl group [UV (MeOH) λmax 1La
band (log ꢀ) ca. 260 nm (4.40)] stereoselectively approached 4b
from the concave face to give the endo adduct 8b (60% yield) along
with the enantiomeric endo adduct 8a (15% yield), the latter being
generated by transfer of 1-ArO to 2-ArO and then to 3-ArO
(Scheme 2).
Figure 3. CD spectra of 1 and isomers 4a and 4b.
To overcome this problem, the 3,4-dimethoxycinnamoyl group
was replaced with a p-bromobenzoate group [UV (MeOH) λmax
1La band (log ꢀ) ca. 244 nm (4.29)], as outlined in Scheme 3.11
The 3,4-dimethoxycinnamoyl group was readily removed by
NaOMe in MeOH to give acetal 9b, which was then reacted with
p-bromobenzoyl chloride to yield the benzoate derivative 10b. No
racemization was observed during this transformation. The CD
spectrum of 10b (Figure 5A) exhibited two weak CD signals at
255 nm (∆ꢀ -11.5) and 237 nm (∆ꢀ +2.5) arising from exciton
coupling. A negative couplet indicates negative helicity between
the benzoate and the biphenyl chromophores corresponding to a
(1S,2R,3R) configuration. The corresponding enantiomer 10a gave
While the enantiomers were readily separated on a Chiralcel OD
column (Figure 2), the CD spectra of neither 8a nor 8b exhibited
clear-cut couplets between the 4-biphenyl and the 3′,4′-dimethoxy-
cinnamoyl groups (Figure 4).

1048 Journal of Natural Products, 2006, Vol. 69, No. 7
Table 1. 1H and 13C NMR Data for 1a
Cardoso et al.
literature values6
b
C
δC
gHMQC δH
gHMBC
COSY
TOCSY
6.95
NOESY 1D
δC
δH, mult., J (Hz)
1′
2′
127.6 s
115.2 d
H-7′; H-8′; H-5′
H-6′; H-7′
128.0
115.1
6.95 (J ) 2.0 Hz)
6.95
7.46; 6.16; 6.68;
6.84
7.04 d (J ) 1.8 Hz)
3′
4′
5′
6′
149.5 s
147.2 s
116.5 d
122.9 d
H-2′; H-5′; H-6′
H-6′, H-5′; H-2′
H-7′; H-6′
149.4
146.8
116.5
122.9
6.68 d (J ) 8.0 Hz)
6.85 dd (J ) 2.0;
8.0 Hz)
6.85
6.68
6.85
6.68
6.68; 6.16; 7.46
6.16; 7.46; 6.68;
6.94
6.76 d (J ) 8.2 Hz)
6.93 dd (J ) 8.2;
1.8 Hz)
H-7′; H-2′; H-5′
7′
8′
9′
1
146.8 d
115.3 d
168.7 s
72.0 d
7.46 d (J ) 16.0 Hz)
H-6′; H-7′
H-2′; H-6′
H-7′; H-8′
H-2
6.16
7.46
6.16
7.46
6.16; 6.84; 6.94
7.46; 6.84; 6.94
146.8
115.8
169.0
73.0
7.58 d (J ) 15.9 Hz)
6.16 d (J ) 16.0 Hz)
6.30 d (J ) 15.9 Hz)
5.23 m
3.62; 2.12; 1.93
5.23; 4.07
4.07; 3.62; 2.12;
1.93
5.23; 4.07; 2.12;
1.93
5.23;3.62; 2.07;
1.98
2.12; 2.07; 3.62;
5.35 m
2
3
73.6 d
71.5 d
3.62 dd (J ) 3.0;
3.0 Hz)
4.07 m
5.23; 4.07; 2.07;
1.98
3.62; 1.98; 2.07
74.8
68.3
3.64 dd (J ) 8.3;
3.1 Hz)
4.14 m
2.07; 1.98; 3.62
4
5
38.2 t
38.9 t
2.07 m-1.98 m
2.12 m-1.93 m
4.07; 2.12
1.93; 5.23
4.07; 2.12
5.23; 3.62; 1.98
36.7
41.5
2.15 m
2.15 m; 1.95 m
1
a Spectra measured in CD3OD at 500 MHz for H NMR and at 125 MHz for 13C NMR: 1H NMR assignments were based on 2D NMR and
HMQC correlations. b Internal standard TMS, δTMS ) 0.00.
Scheme 1
Scheme 2
Scheme 3
Experimental Section
an opposite split CD curve (Figure 5B). Comparison of the CD
spectrum of naturally occurring 1 (Figure 3) with those of 10b and
10a (Figure 5) established the absolute configuration of 1 as
(1S,2R,3R) (Figure 6).
General Experimental Procedures. IR spectra were recorded on a
Nicolet FT-IR model EMACT-40 and a Perkin-Elmer 1600 FTIR
spectrophotometer in the range 500-4000 cm-1. 1H NMR, 13C NMR,

Absolute Configuration of a Compound from Chimarrhis turbinata
Journal of Natural Products, 2006, Vol. 69, No. 7 1049
and identified by Dr. Marina Thereza V. do A. Campos from Botanic
Garden Institute. A voucher specimen was deposited in the Herbarium
of the Botanic Garden Institute, Sa˜o Paulo, Brazil, with voucher code
Lopes-51.
Extraction and Isolation of Phenolics. Dried and powdered leaves
of C. turbinata (1.2 kg) were extracted with EtOH to afford 57.12 g of
dry residue, which was dissolved in MeOH/H2O (8:2) and partitioned
with n-hexane. The aqueous alcoholic fraction was evaporated to
roughly MeOH/H2O (6:4) and then extracted successively with CH2-
Cl2, EtOAc, and n-BuOH. The dried EtOAc extract (4.16 g) was
dissolved in MeOH (5 mL) and submitted to gel filtration over Sephadex
LH-20. A total of 25 fractions of 25 mL each were collected and pooled
according to their TLC profiles (CHCl3/MeOH/H2O, 65:30:5). Fractions
A-6/7 and A-8 to A-12 showed antioxidant activities and were further
purified by HPLC. Fractions A-8 to A-12 yielded the compounds
described elsewhere.5
Fraction A-6/7 (599.0 mg) was purified by gel filtration over
Sephadex LH-20. Thirty-six fractions of 10 mL each were collected
and pooled according to their TLC profiles (CHCl3/MeOH/H2O, 65:
30:5). Fractions 20-30 showed antioxidant activity and were pooled
and purified by preparative HPLC (isocratic elution; H2O/MeCN, 82:
12; 12.0 mL/min flow rate) to afford 10 subfractions. Subfraction B-3
(97.2 mg) was purified by preparative HPLC (isocratic elution; H2O/
MeCN, 85:15; 12.0 mL/min flow rate) to yield 18 fractions; fraction
12 (8.8 mg) was identified as compound 1. Subfraction B-4 (17.2 mg)
was purified by semipreparative HPLC (isocratic elution; H2O/MeCN,
80:20; 10.0 mL/min flow rate) to yield compounds 2 (8.0 mg) and 3
(2.3 mg). The EIMS of 2 and 3 presented pseudomolecular ions at m/z
369 [M + H]+, 391 [M + Na]+, and 407 [M + K]+ and fragment ions
at m/z 163. The 1H and 13C NMR spectra of 2 and 3 were identical to
the published data for chlorogenic acid methyl ester with trans and cis
relative configurations, respectively.12
Synthesis of 1-(3′,4′-Dimethoxycinnamoyl)cyclopentane-2,3-diol
(4). To a solution of cyclopentane-1,2,3-triol (5; 5.7 mg; 48 µmol) in
tetrahydrofuran (THF; 1.5 mL), maintained at room temperature under
argon, were added 1-(3′,4′-dimethoxycinnamoyl)-1,2,4-triazole (6; 11
mg, 41 µmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU; 16 mg,
100 µmol), and the mixture was stirred for 12 h. The reaction mixture
was concentrated in vacuo, and the crude product was purified by TLC
(EtOAc) and by HPLC (isocratic elution; n-hexane/2-PrOH, 75:25) to
give 4a (4.4 mg; 30% yield; tR 11 min) and 4b (4.4 mg; 30% yield; tR
26 min) as colorless oils: UV (MeOH) λmax (log ꢀ) 322 (4.21), 295
Figure 4. CD spectra of 8a and 8b.
gCOSY, gHMQC, gHMBC, TOCSY, and NOESY spectra were
recorded on a Varian Unity 500 spectrometer at 25 °C and referenced
to the residual solvent resonances of CD3OD at δ 3.33 and 49.0,
1
respectively, for H and 13C NMR using TMS as internal standard.
1
(4.12) nm; H NMR (CD3OD, 300 MHz) δ 7.67 (1H, d, J ) 16 Hz),
EIMS spectra were obtained on a VG Platform Fisons mass spectrom-
eter.
7.21-7.16 (2H, m), 6.97 (1H, d, J ) 8.3 Hz), 6.45 (1H, d, J ) 16
Hz), 5.11-5.09 (1H, m), 4.11-4.08 (1H, m), 4.02 (1H, t, J ) 4.6 Hz),
3.86 (6H, s), 2.01-1.82 (4H, m); HRFABMS m/z 308.1256 (calcd for
C16H20O6, 308.1260).
TLC was performed using precoated silica gel 60 PF254 plates
(Merck): separated components were visualized under UV light and/
or by spraying with anisaldehyde-H2SO4 reagent followed by heating
at 120 °C. Column chromatography was carried out using a Pharmacia
Sephadex LH-20 column (88.0 × 2.0 cm i.d.) eluted isocratically with
MeOH. HPLC separations were performed on a Varian Prep Star
Dynamax model SD-1 equipped with a Supelco C-18 semipreparative
column (250 × 10 mm i.d.; 5 µm) or a Phenomenex ODS Luna 10
preparative column (250 × 21.20 mm; 5 µm) protected by a Phenomex
ODS Luna 10 precolumn (50 × 10 mm i.d.; 5 µm). Components were
detected using a Varian model 320 chromato-integrator connected to a
UV detector set at 280 nm.
Synthetic reactions were carried out under an atmosphere of argon
in flame- or oven-dried glassware with magnetic stirring unless
otherwise indicated. UV-visible spectra were measured at 25 °C on a
Perkin-Elmer Lambda 40 spectrophotometer, and CD spectra were
recorded on a Jasco-810 spectrophotometer. 1H NMR spectra were
determined on a Bruker DPX-300 spectrometer and referenced to the
residual proton solvent resonances of CD3OD at δ 3.30 ppm. Low-
and high-resolution FABMS were measured on a JEOL JMS-DX303
HF mass spectrometer using a glycerol matrix and Xe ionizing gas.
HPLC analyses and the preparation and resolution of synthetic
compounds were performed using a Shimadzu separation HPLC
(Shimadzu, Kyoto, Japan), which consisted of the two LC 10 AD VP
pumps, a UV-vis detector (SPD-M10AV VP), and manual sampler
equipped with a Dicel Chiralcel OD column (250 × 4.6 mm i.d.; 10
µm): the mobile phase was n-hexane/2-propanol at a flow rate of 1
mL/min and detection at 254 nm.
Synthesis of 1-(3′,4′-Dimethoxycinnamoyl)-2,3-[(4′-biphenyl)m-
ethylenedioxy]cyclopentane (4′ endo) (8b). To a solution of 4b (2.0
mg; 6.5 µmol) in benzene (0.3 mL) maintained at room temperature
under argon was added 4-biphenylcarboxaldehyde (5.3 mg; 29 µmol)
and p-TsOH monohydrate (50 µg; 0.5 µmol) and the mixture stirred
for 2 h. The reaction mixture was concentrated in vacuo, and the crude
product was purified by TLC (n-hexane/EtOAc, 2:1) and by HPLC
(isocratic elution; n-hexane/2-PrOH, 95:5) to give 8b (1.4 m; 46% yield;
tR 42 min) and 8a (0.4 mg; 13% yield; tR 50 min) as colorless oils:
1
UV (MeCN) λmax (log ꢀ) 324 (4.26), 246 (4.46) nm; H NMR (CD3-
OD, 300 MHz) δ 7.68-7.55 (7H, m), 7.45-7.41 (2H, m), 7.37-7.33
(1H, m), 7.08-7.03 (2H, m), 6.82 (1H, d, J ) 8.3 Hz), 6.37 (1H, d, J
) 16 Hz), 5.80 (1H, s), 4.97-4.92 (1H, m), 4.79 (1H, t, J ) 5.4 Hz),
4.74 (1H, t, J ) 5.4 Hz), 3.89 (3H, s), 3.86 (3H, s), 2.21-2.04 (3H,
m), 1.69-1.62 (1H, m); HRMS m/z 472.1885 (calcd for C29H28O6,
472.1886).
Synthesis of 1,2-[(4′-Biphenyl)methylenedioxy]cyclopentane-3-ol
(4′ endo) (9b). To a solution of 8b (1.4 mg; 3.0 µmol) in MeOH/
CHCl3 (1:1; 0.2 mL) maintained at room temperature was added 2.5
M NaOMe/MeOH (30 µL), and the mixture was stirred for 6 h. The
reaction mixture was concentrated in vacuo, and the crude product was
purified by TLC (n-hexane/EtOAc, 2:1) to give 9b (0.80 mg; 95% yield)
1
as a colorless oil: UV (MeCN) λmax (log ꢀ) 252 (4.19) nm; H NMR
(CD3OD, 300 MHz) δ 7.62-7.56 (6H, m), 7.45-7.23 (3H, m), 5.81
(1H, s), 4.69 (1H, t, J ) 5.5 Hz), 4.50 (1H, t, J ) 5.4 Hz), 4.02-3.92
(1H, m), 2.34 (1H, d, J ) 10 Hz), 2.07-1.94 (2H, m), 1.88-1.76 (1H,
m), 1.59-1.47 (1H, m); HRMS m/z 283.1333 (calcd for C18H18O3,
Plant Material. Leaves of Chimarrhis turbinata DC. Prodr. were
collected in the Reserva do Viro, Bele´m, PA, Brazil, in February 2000,

1050 Journal of Natural Products, 2006, Vol. 69, No. 7
Cardoso et al.
Figure 5. (A) CD spectrum of 10b and assignment of absolute configuration. (B) CD spectrum of 10a.
References and Notes
(1) Boom, B. M.; Campos, M. T. V. A. Bot. Mus. Paraense Emilio Goeldi
1991, 7, 223-247.
(2) Cardoso, C. L.; Silva, D. H. S.; Tomazela, D. M.; Verli, H.; Young,
M. C. M.; Furlan, M.; Eberlin, M. N.; Bolzani, V. S. J. Nat. Prod.
2003, 66, 1017-1021.
(3) Castro-Gamboa, I.; Cardoso, C. L.; Silva, D. H. S.; Cavalheiro, A.
J.; Furlan, M.; Bolzani, V. S. J. Braz. Chem. Soc. 2003, 14, 771-
776.
Figure 6. Absolute configuration of compound 1.
(4) Cardoso, C. L.; Silva, D. H. S.; Bolzani V. S. Abstracts of the 41st
Annual Meeting of the American Society of Pharmacognosy, New
Jersey, 2002.
(5) Cardoso, C. L. Phytochemical and Biological Studies of Chimarrhis
turbinata DC. Prodr. (Rubiaceae). Ph.D. Thesis, Universidade
Estadual Paulista-UNESP, Araraquara, Sa˜o Paulo, Brazil, 2003, pp
158-159.
(6) Wang, H.; Nair, M. G.; Strasburg, G. M.; Booren, A. M. J.; Gray, I.
J. Nat. Prod. 1999, 62, 86-88.
(7) Gargiulo, D.; Ikemoto, N.; Odingo, J.; Bozhkova, N.; Iwashita, T.;
Berova, N.; Nakanishi, K. J. Am. Chem. Soc. 1994, 116, 3760-3767.
(8) Cai, G.; Bozhkova, N.; Berova, N.; Nakanishi, K. J. Am. Chem. Soc.
1993, 115, 7192-7198.
283.1334). The enantiopurity was checked by HPLC (isocratic elution;
n-hexane/2-PrOH, 85:15; tR 8 min).
Synthesis of 1-(p-Bromobenzoyl)-2,3-[(4′-biphenyl)methylene-
dioxy]cyclopentane (4′ endo) (10b). To a solution of 9b (0.80 mg;
2.8 µmol) in THF (0.1 mL) maintained at room temperature were added
p-bromobenzoyl chloride (3.0 mg; 14 µmol) and triethylamine (10 µL),
and the mixture was stirred for 12 h. The reaction mixture was
concentrated in vacuo, and the crude product was purified by TLC (n-
hexane/EtOAC, 3:1) to give 10b (0.64 mg; 49%) as a colorless oil:
UV (MeCN) λmax (log ꢀ) 245 (4.61) nm; 1H NMR (CD3OD, 300 MHz)
δ 7.91-7.88 (2H, m), 7.61-7.31 (11H, m), 5.79 (1H, s), 5.04-4.97
(1H, m), 4.84 (1H, t, J ) 5.4 Hz), 4.75 (1H, t, J ) 5.4 Hz), 2.32-2.04
(3H, m), 1.73-1.62 (1H, m); HRMS m/z 463.0550 (calcd for
C25H2279BrO4, 463.0545). The enantiopurity was checked by HPLC
(isocratic elution; n-hexane/2-PrOH, 99:1; tR 27 min).
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Acknowledgment. This work was funded by the Fundac¸a˜o de
Amparo a` Pesquisa do Estado de Sa˜o Paulo (FAPESP) as part of the
Biodiversity Virtual Institute Program (Biota-FAPESP; www.bio-
tasp.org.br) in the form of grant no. 03/02176-7 awarded to V.S.B.
(Principal Investigator). V.S.B., D.H.S.S., I.C.-G., and C.L.C. acknowl-
edge CNPq and FAPESP for Researcher and Ph.D. fellowships. The
authors wish to thank Columbia University (NewYork) for providing
grant fellowship complementation for C.L.C., and for CD exciton
studies.
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