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The Constituents of Lindera glauca
Yuh-Chwen Chang
a,b
( ), Fang-Rong Chang
b
( ) and Yang-Chang Wu*
b
( )aDepartment of Chemical Engineering, Kao Yuan Institute of Technology, Kaohsiung county, Taiwan, R.O.C.
bGraduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.
Twenty-eight compounds including seven alkaloids, (+)-3-chloro-N-formylnornantenine (1), (+)-N-
formylnornantenine (2), (+)-boldine (3), (+)-norboldine (4), (-)-norboldine (5), lycicamine (6), and tetrahydro-
berber ine (7); four flavonoids, kaempferol (8), kaempferol-3-O-arabinoside (9), quercetin (10), and
quercetin-3-O-rhamnoside (11); one butanolide, akolactone A (12); onep-quinone, 2,6-dimethoxy-p-quinone
(13); one cyclohex-2-en-1-one, blumenol A (14); six benzenoids, methylparaben (15),p-hydroxybenzoic acid
(16), vanillic acid (17), syringic acid (18), 3,4,5-trimethoxybenzoic acid (19), and 3-(3,4-dihydroxyphenyl)
propionic acid (20); one diterpene, phytol (21); one triterpene, squalene (22); six steroids, -sitosterol (23),
-sitostenone (24), stigmasta-4,22-dien-3-one (25), 6 -hydroxy- -sitostenone (26), 6 -hydroxystigmasterone
(27), and -sitosteryl-D-glucoside (28) were isolated from the aerial part ofLindera glauca. These compoundswere characterized and identified by physical and spectral method. All compounds were isolated for the first
time from this plant. Among them, (+)-3-chloro-N-formylnornantenine (1) is a new one.
INTRODUCTION
Lindera glauca Sieb.& Zucc.(Lauraceae) is a small de-
ciduous tree growing in the forests at low altitudes in Japan,
China and Taiwan.1
Previously, three alkaloids, nineteen fatty
acids, eight monoterpenes, five sesquiterpenes, two naph-
thalenes, and eleven butanolideshave been reported from this
plant.2-8 As part of our continuing investigation of the phyto-
chemical and bioactive compounds of Formosan Lauraceous
plants, the methanol extract of this plant was subjected to sol-
vent partition and chromatographic separation to characterize
twenty-eight pure compounds. Among them, 1is a new com-
pound, and known compounds 2~28were isolated for the first
time from this species. The present paper deals with the isola-
tion and characterization of the isolated components.
RESULTS AND DISCUSSION
A methanolic extract ofL. glaucawas concentrated to
obtain a residue and then partitioned between CHCl3and H2O.
The aqueous layer was partitioned with n-BuOH. Each layer
was concentrated and subjected to chromatography. Fifteen
compounds including five alkaloids, (+)-3-chloro-N-formyl-
nornantenine (1), (+)-N-formylnornantenine9(2), (+)-nor -
boldine10
(4), (-)-norboldine11,12
(5), and lysicamine13
(6); one
butanolide, akolac tone A (12); one benzenoid, methyl-
paraben14
(15); one diterpene, phytol (21); one triterpene,
squalene (22); and five steroids, -sitosterol13,15 (23), -
sitostenone13 (24), stigmasta-4,22-dien-3-one13 (25), 6 -
hydroxy- -sitostenone13 (26), 6 -hydroxystigmasterone13
(27), and -sitosteryl-D-glucoside13
(28) were obtained from
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374 J. Chin. Chem. Soc., Vol. 47, No. 2, 2000 Chang et al.
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the chloroform layer. Thirteen compounds including two al-
kaloids, (+)-boldine11,12
(3) and tetrahydroberberine16
(7);
four flavonoids, kaempferol17 (8), kaempferol-3-O-
arabinoside18 (9), quercetin17 (10 ), and quercetin-3-O-
rhamnoside19 (11 ); one p-quinone, 2,6-dimethoxy-p-
quinone20 (13); one cyclohex-2-en-1-one, blumenol A21,22
(14); five benzenoids,p-hydroxybenzoic acid14
(16), vanillic
acid14
(17), syringic acid14
(18), 3,4,5-trimethoxybenzoic
acid14 (19), and 3-(3,4-dihydroxyphenyl) propionic acid23
(20) were obtained from the n-Butanol layer. Among them 1is
a new compound, and others are known compounds which
were isolated for the first time from this plant and character-
ized by comparison of their physical and spectral data (UV,
IR, NMR and MS) with values previously reported in the liter-
ature.
The alkaloid 1was recrystallized from methanol as col-
orless needles. Its molecular formula was established as
C20H18O5NCl by HREI mass spectrometry m/z M+
(found
387.0867, calcd 387.0874), with a mp over 300 C. The IR
spectrum with peaks at 1660 and 1620 cm-1, was suggestive of
an amidic functional group. The UV absorptions showed max
at 272sh, 281, 302, and 312sh nm, indicating alkaloid 1pos-
sessed a 1, 2, 3, 9, 10-substituted aporphine24
. EI-MS spec-
trum showed that one chlorine is bonded to alkaloid 1with a
spectrum of 3 to 1 ratio at m/z (rel. int %): 387(23, M+)/389;
351(52, [M-Cl]+)/353; 329(100)/331. The molecular ion m/z
387(23, M+)/389, and base peak m/z329(100)/331 are due to
loss of (CH2-N-CHO+H) from the molecular ion. It followed
that the amidic function was in the shape of an N-formyl
group. Moreover, the two species were actually present in so-
lution, due to isomerism about the amidic bond could be im -
mediately derived from the 1H-NMR spectrum. Broad down-
field singlets at 8.25 and 8.36 represented theN-formyl pro-
ton. The integrals of these peaks indicated that the isomers
were present in a ratio of 2:1.
The spectra for the two isomers could be clearly differ-
entiated, even though the two isomers could not be separated.
While the differences in chemical shifts were minimal in the
case of the methoxyl and methylenedioxy signals, they were
clearly noticeable for the aromatic protons, with signals at
6.78 (H-8) and 7.91 (H-11) for the major isomer 1a, and at
6.76 and 7.92 for the minor isomer 1b . The divergence be-
tween the two isomers was quite prominent in the aliphatic
range. Some of the more salient differences in chemical shifts
occurred in the resonances for the hydrogens bonded to C-5,
C-6a and C-7. For the major isomer 1a, the signals for H-6a
The Constituents ofLindera glauca J. Chin. Chem. Soc., Vol. 47, No. 2, 2000 375
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and H-7 were downfield at 4.91 and 2.97, respectively. On
the other hand, for 1b, these two protons are relatively upfield
at 4.45 and 2.75, respectively. For both isomers, the H-7
signals were characterized by small coupling constants withH-6a (ca. 4.0 Hz), but the H-7 signals were denoted by large
constants (ca. 14.0 Hz).
The disparity in geometry between the two isomers also
came to the fore when NOESY measurements were obtained.
In particular, the proximity of the formyl proton to H-5 (
3.86) in the major isomer and to H-6a ( 4.45) in the minor iso-
mer was clearly evident. With both isomers, a strong nOe
could be observed between H-7 and H-8 (see Fig. 1). A simi-
lar observation for alkaloid 2has been found in the literature.9
In view of alkaloid 2, the H-3 signal disappeared in
those of 1. It strongly indicates that the chlorine atom was sub-
stituted at 3-position. Since neither chlorine gas nor HCl was
even used during extraction or chromatography, an artifact is
excluded. On the basis of the result mentioned above, the
structure was thus determined as (+)-3-chloro-N-formyl-
nornantenine. In addition, the biological activities of these
compounds are currently under investigation.
EXPERIMENTAL SECTION
General Methods
Uncorrected melting points were determined on a
Mel-Temp II apparatus. Optical rotation was taken on a Jasco
DIP-370 digital polarimeter. Ultraviolet (UV) and infrared
(IR) spectra were obtained using a Hitachi U-2000 spectro-
photometer and a Hitachi 260-30 spectrophotometer, respec-
tively. NMR spectra were recorded with a Varian Gemini
NMR Spectrometer (200 MHz) and a Varian Unity Plus NMR
Spectrometer (400 MHz) using TMS as an internal standard.
Mass Spectra (MS) were recorded on a JEOL JMS-HX 110
mass spectrometer. Active charcoal (Wako) and silica gel 60
(E. Merck, 230-400 mesh) were used for open column chro-
matography and precoated silica gel plates (E. Merck,
Kieselgel 60 F-254, 0.25 mm) were used for preparative TLC.
Plant MaterialL. glauca Sieb. Zucc.(Lauraceae) was collected from
Taipei county, Taiwan in July 1996. A voucher specimen is on
deposit in the Graduate Institute of Natural Products,
Kaohsiung Medical University, Kaohsiung, Taiwan, Republic
of China.
Extraction and Separation
Air-dried, aerial parts (9.8 Kg) of L. glauca were ex-
tracted repea tedly with MeOH at room temperature. The
methanolic extracts were concentrated and partitioned be-
tween chloroform and water to form a chloroform layer and an
aqueous layer. The chloroform layer was concentrated to
leave a brownish viscous residue (8.8 g). The residue was
placed on a silica gel column and eluted with CHCl3 which
was gradually enriched with MeOH to afford eleven fractions.
Fr.2 (2.1 g) eluted with a gradient of n-hexane/CHCl3/EtOAC
was separated using silica gel CC and prep. TLC and gave
(+)-3-chloro-N-formylnornantenine (1) (3 mg), (+)-N-
formylnornantenine (2)(5 mg),akolactone A (12) (3 mg),
phytol (21) (20 mg) and squalene (22) (20 mg), respectively.
Fr.5 (1.4 g) eluted with CHCl3 was isolated using repeatedly
silica gel CC and prep. TLC (CHCl3) and gave -sitosterol
(23) (50 mg). (+)-norboldine (4) (10 mg), (-)-norboldine (5) (4
mg)andmethylparaben (15) (10 mg) were obtained from Fr.7
(1.3 g) by means of repea tedly silica gel CC eluting with
CHCl3-MeOH (20:1). Fr.8 (0.6 g) eluted with CHCl3-MeOH
(15:1) was further separated using silica gel CC and prep.
TLC and gave lysicamine (6) (5 mg). Fr.10 (0.8 g) eluted with
CHCl3-MeOH (10:1) was separated using silica gel CC and
prep. TLC and gave -si tostenone (24) (10 mg), stigmasta-
4,22-dien-3-one (25)(15 mg), 6 -hydroxy- -sitostenone (26)
(10 mg) and 6 -hydroxystigmasterone (27) (10 mg), respec-
tively. Fr.11(1.1 g) eluted with CHCl3-MeOH (8:1) was fur -
ther separated using silica gel CC and gave -sitosteryl-D-glucoside (28) (30 mg).
The aqueous layer was partitioned with n-Butanol to
give a n-Butanol layer and an aqueous layer. The n-Butanol
layer was concentrated (4.8 g) and chromatographed over sil-
ica gel using CHCl3/EtOAC/MeOH as an eluent to produce
ten fractions. Fr.3 (0.8 g) eluted with CHCl3was further puri-
fied in silica gel column using the same solvent to obtain com-
pound 2,6-dimethoxy-p-quinone (13) (10 mg). Fr.4 (2.3 g)
eluted with CHCl3-MeOH (10:1) was further separated using
silica gel CC and prep. TLC and gave kaempferol (8) (10 mg),
quercetin-3-O-rhamnoside (11) (50 mg); blumenol A (14) (30
mg),p-hydroxybenzoic acid (16) (20 mg), vanillic acid (17)
376 J. Chin. Chem. Soc., Vol. 47, No. 2, 2000 Chang et al.
Fig. 1. NOESY correlations for 1.
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2113-M-037-009)
Received August 4, 1999.
Key Words
Lindera glauca; Alkaloids; Flavonoids;
Benzenoids; Diterpenes; Triterpens; Steroids;
(+)-3-Chloro-N-formylnornantenine.
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