Novel phenylpropanoids and lignans from Illicium verum

Article abstract of DOI:10.1021/np9800553

Nine new phenylpropanoids (2-7, 10, 12, and 14) and two compounds representing novel structural classes of 7-O-8' and 7-O-8'.8-O-7' lignans (8 and 9, respectively) have been isolated from Illicium verum and their structures established by two-dimensional NMR. Most of these compounds appear to be biogenetically derived from threo-anethole glycol: relative stereochemistries for some members of this series were established by NOESY; absolute stereochemistries of others were determined by formation of Mosher esters.

Full text of DOI:10.1021/np9800553

J . Nat. Prod. 1998, 61, 987-992
987
Novel P h en ylp r op a n oid s a n d Lign a n s fr om Illiciu m ver u m
Lai-King Sy and Geoffrey D. Brown*
Chemistry Department, The University of Hong Kong, Pokfulam Rd., Hong Kong
Received February 19, 1998
Nine new phenylpropanoids (2-7, 10, 12, and 14) and two compounds representing novel
structural classes of 7-O-8′ and 7-O-8′.8-O-7′ lignans (8 and 9, respectively) have been isolated
from Illicium verum and their structures established by two-dimensional NMR. Most of these
compounds appear to be biogenetically derived from threo-anethole glycol: relative stereochem-
istries for some members of this series were established by NOESY; absolute stereochemistries
of others were determined by formation of Mosher esters.
Illicium verum Hook f. (Illiciaceae, Chinese star anise)
is an evergreen tree indigenous to southern China, used
by local people as a stimulant and carminative.1 It is
easily confused with the extremely posionous I. anisa-
tum (containing the GABA antagonist anisatin, which
is reported to be the most powerful poison of plant
origin, and related sesquiterpenes), which is found in
the same geographical region and which produces
morphologically similar fruits.2 Previous chemical in-
vestigations of I. verum have yielded 4-ethoxyphenol,
anisyl ketone,3 the phenylpropanoid, anisoxide,4 and the
sesquiterpenes veranisatins A and B,5 as well as various
cinnamic acid derivatives.6
Resu lts a n d Discu ssion
Extraction of the leaves of I. verum with CH2Cl2
yielded nine new phenylpropanoid derivatives (2-7, 10,
12, and 14) and two new lignans (8 and 9). Many of
these compounds are apparently derived from the
simple phenylpropanoid diol, threo-anethole glycol (1a ),
which was also present as a significant component of
1
the extract. 13C and H NMR assignments for 1a and
for all compounds reported in this paper were rigorously
determined by means of 2D-NMR (HSQC, HMBC, and
1H-1H COSY) (Tables 1 and 2).
Compound 1 was isolated from I. verum predomi-
nantly as the threo form as shown by NMR; in particu-
1
lar, a J 7,8 coupling constant of 7.8 Hz in the H NMR
spectrum is considered diagnostic for this diastereoiso-
mer.7 Smaller amounts of the erythro isomer (1b) were
also obtained, for which this coupling constant has been
shown previously to have a consistently smaller value
(ca. 4 Hz).7 1H and 13C chemical shifts for these two
diastereoisomers of anethole glycol also agreed with
those reported previously.7 A pure sample of 1a had a
significant optical rotation ([R]D +7.7°). Although both
threo and erythro forms of anethole glycol have been
reported from nature, there is apparently no data
available in the literature concerning optical rotations
of either the 7R,8R or 7S,8S threo isomers with which
to make a comparison with our sample from I. verum.
Consequently, we endeavored to determine the absolute
configuration at the 7- and 8-positions of 1a by forma-
tion of esters with the two enantiomers of R-methoxy-
R-(trifluoromethyl)phenylacetyl chloride ((S)-(+)-MTPCl
and (R)-(-)-MTPCl).8 In the event, treatment of 1a with
the (S)-(+) enantiomer of MTPCl yielded four com-
pounds (1c-f), which were separable by HPLC; simi-
larly, application of (R)-(-)-MTPCl yielded the corre-
sponding four mirror image esters 1g-j, respectively.
(Note: R/S nomenclature for the R-methoxy-R-(trifluo-
romethyl)phenylacetate (MTPA) moiety of the esters so
formed is reversed with respect to the acid chloride
derivatizing agent.) Formation of four such distinct
isomers from esterification with each enantiomer of
* To whom correspondence should be addressed. Tel.: 852-2859
7915. Fax: 852-2857 1586. E-mail: GDBROWN@HKUCC.HKU.HK.
S0163-3864(98)00055-X CCC: $15.00
© 1998 American Chemical Society and American Society of Pharmacognosy
Published on Web 07/11/1998

988 J ournal of Natural Products, 1998, Vol. 61, No. 8
Ta ble 1. 13C NMR Assignments (δ) for 1-7
Sy and Brown
atom
1a
1b
2
3
4
5
6
7a
1
2/6
3/5
4
159.4
113.9
128.1
133.3
79.2
159.4
113.8
128.0
132.5
77.3
159.6
114.0
128.3
132.3
77.0
159.7
114.0
128.5
129.9
80.7
159.6
114.1
127.8
130.7
84.6
158.0
113.7
129.7
131.7
59.5
158.4
113.5
130.7
130.4
59.3
158.5
114.3
129.6
133.8
58.9
7
8
72.3
71.3
75.1
70.4
81.3
72.8
68.9
70.3
9
18.8
17.5
16.6
18.8
16.4
22.6
22.2
21.4
1′
163.5
113.7
131.7
122.7
166.2
55.3
163.6
113.7
131.8
122.5
165.7
55.3
160.4
113.8
128.0
130.7
104.0
55.3
158.8
113.4
128.0
135.3
80.4
158.9
113.4
128.0
134.2
75.2
158.2
114.0
129.0
135.1
2′/6′
3′/5′
4′
7′
1-OMe
1′-OMe
55.3
55.3
55.04
55.14
55.24
55.18
55.3
55.2
55.5
55.5
55.4
a
All assignments for 1-4 may be interchanged (as a group) with those for 1′-4′.
Ta ble 2. 1H NMR Assignmentsa (δ) for 1-7
atom
1a
1b
2
3
4
5
6
7b
2/6
3/5
7
6.87 (d, 8.7)
7.23 (d, 8.7)
4.28 (d, 7.8)
6.90 (d, 8.6)
7.29 (d, 8.6)
4.60 (d, 4.5)
6.89 (d, 8.6)
7.32 (d, 8.6)
4.72 (d, 7.4)
6.88 (d, 8.7)
7.34 (d, 8.7)
5.71 (d, 7.2)
6.91 (d, 8.7)
7.34 (d, 8.7)
4.57 (d, 8.1)
6.63 (d, 8.8)
6.74 (d, 8.8)
2.75 (m)
6.74 (d, 8.7)
6.89 (d, 8.7)
2.87 (dd,
6.86 (d, 8.7)
7.28 (d, 8.7)
3.71 (d, 8.7)
8.5, 4.5)
8
3.82 (m)
4.00 (m)
5.30 (dq,
7.4, 6.4)
4.19 (dq,
7.2, 6.3)
4.04 (dq,
8.1, 6.1
4.36 (dq,
9.1, 6.2)
4.23 (dq,
8.5, 6.2)
4.45 (dq,
8.7, 6.1)
9
1.00 (d, 6.3)
1.10 (d, 6.4)
1.17 (d, 6.4)
6.94 (d, 8.9)
8.02 (d, 8.9)
1.13 (d, 6.3)
6.92 (d, 8.9)
8.03 (d, 8.9)
1.42 (d, 6.1)
6.93 (d, 8.7)
7.48 (d, 8.7)
6.17 (s)
3.82 (s)
3.82 (s)
0.94 (d, 6.2)
6.66 (d, 8.7)
6.98 (d, 8.7)
4.97 (d, 9.8)
3.70 (s)
1.06 (d, 6.2)
6.77 (d, 8.7
6.99 (d, 8.7)
5.16 (d, 4.5)
3.78 (s)
1.18 (d, 6.1)
6.82 (d, 8.7)
7.18 (d, 8.7)
2′/6′
3′/5′
7′
1-OMe
1′-OMe
3.81 (s)
3.81 (s)
3.81 (s)
3.87 (s)
3.80 (s)
3.86 (s)
3.78
3.76
3.71 (s)
3.77 (s)
a
b
Multiplicity and coupling constants (Hz) indicated in parentheses. Assignments for 2-6 may be interchanged (as a group) with
those for 2′-6′.
F igu r e 2. Chemical shift differences ((S)-OMTP - (R)-OMTP)
between diastereoisomeric pairs of compounds formed in the
derivatization of threo-7-(4-methoxybenzoloyl)anethole glycol
(3, 7S/8S and 7R/8R) by (S)-(+)- and (R)-(-)-MTPCl. Com-
pounds 3a and 3d derived from threo 7R,8R isomer; com-
pounds 3b and 3c derived from 7S,8S isomer.
demonstrated unambiguously that compound 1a from
I. verum is indeed the threo form of anethole glycol (as
previously supposed from the value of J 7,8) and is an
approximately 2:1 mixture of 7S,8S and 7R,8R isomers.
Compound 2 is the 8-(4-methoxybenzoloyl) derivative
of anethole glycol as shown by a correlation between
C-7′ of the benzoyl substituent and H-8 of the anethole
glycol moiety in the HMBC spectrum. The coupling
constant between H-7 and H-8 in 1H NMR suggests
threo stereochemistry for this natural product, consis-
tent with 2 being derived from 1a . Compound 3 is the
7-(4-methoxybenzoloyl) derivative of anethole glycol (as
shown by a correlation in HMBC from the benzoyl
carbonyl to H-7). An attempt was made to establish the
absolute stereochemistry of the 8-secondary hydroxyl in
3 by formation of Mosher esters using both (S)-(+)- and
(R)-(-)-MTPCl as previously.8 Derivatization with (S)-
(+)-MTPCl yielded two diastereiosmers (3a and 3b),
while use of (R)-(-)-MTPCl yielded the two correspond-
ing mirror images (3c and 3d ). Analysis of chemical
F igu r e 1. Chemical shift differences between diastereoiso-
meric pairs of compounds formed from the derivatization of
threo-anethole glycol (1a , 7S/8S and 7R/8R) by (S)-(+)- and
(R)-(-)-MTPCl. From calculated differences ((S)-MTPA) -((R)-
MTPA) 1c, 1h , 1f, and 1i are derivatives of the 7R,8R threo
isomer (at the 7- and 8- positions), while 1g, 1d , 1j, and 1e
are derived from the 7S, 8S isomer.
MTPCl is only possible if compound 1 is actually present
as a mixture of 7R,8R and 7S,8S forms and if MTPA
esters are formed at both the 7-OH and 8-OH positions.
1
Detailed analysis of H chemical shift differences be-
tween (S)-MTPA and (R)-MTPA derivatives for each of
the four possible products (i.e., ∆ δ1H ((S)-MTPA) - ((R)-
MTPA) for 1g-1d , 1j-1e, 1h -1c and 1i-1f), according
to the preferred conformations normally assumed for
MTPA esters8 (Figure 1), confirmed this supposition and

Phenylpropanoids and Neolignans from Illicium verum
J ournal of Natural Products, 1998, Vol. 61, No. 8 989
ously determined for proposed biogenetic precursors
1-3.
Compounds 5 and 6 are diastereoisomers that appar-
ently arise from direct linkage of a C6C1 substituent at
the reduced 7-position of anethole glycol. Derivatization
of either of the 1,3-diols 5 or 6 with 2,2-dimethoxypro-
pane9) yielded an identical cyclic product 6a , for which
relative stereochemistry around the new six-membered
ring could be determined by NOESY (Figure 3). This
surprising result may be due to the ease of formation
of a phenyl-stabilized carbocation at the 7′ position
under the acid conditions of the derivatization, which
would favor rapid ring opening and closing of the ketal
and accompanying epimerization at C-7′ to yield the
thermodynamically more stable all-equatorially substi-
tuted 1,3-dioxan (Figure 3). Formation of the stilbene
6b as a major byproduct of this reaction is also simply
explained by the above mechanism and lends support
to this hypothesis. Derivatization of 5 and 6 as ketals
thus seemed to show that these compounds are diaste-
reoisomeric at the 7′-position; this is consistent with
their formation from the nonstereospecific addition of
a C6C1 unit to a C6C3 phenylpropanoid derived from
anethole glycol, as proposed above. Compound 7 is a
one-carbon-deficient homologue of 5/6, possibly formed
by the analogous addition of a C6 unit. The two
aromatic rings in 7 are diastereotopic and gave similar
but distinguishable NMR resonances, which were con-
fidently assigned using 2D-NMR methodology employed
throughout this paper.
F igu r e 3. NOESY correlations used in assigning relative
configuration of 4, 6a , and 9 indicated by arrows from 1H to
1H.
shift differences between the two diastereoisomeric
pairs8 (i.e., ∆ δ1H ((S)-MTPA) - ((R)-MTPA) for 3d -3a
and 3c-3b) confirmed the presumed threo stereochem-
istry and indicated that compound 3 was an approxi-
mately 1:1 mixture of 7R,8R and 7S,8S isomers (Figure
2). Given the tendency to partial or complete racem-
ization observed for compounds 1 and 3, no further
attempts were made to establish the absolute stereo-
chemistry of other novel phenylpropanoid and derived
compounds (2, 4-10, and 12) described in this paper;
relative stereochemistry only, as determined by NMR,
is reported. It is proposed that most of these compounds
are at least partially racemic; for simplicity, structures
are drawn with relative stereochemistry corresponding
to the 7S,8S stereoisomer of threo-anethole glycol only.
Compound 4 can be envisaged as being formed from
either 2 or 3 by reduction of the benzoyl ester linkage
accompanied by intramolecular ketal formation with a
free -OH group in the phenylpropanoid moiety. Rela-
tive stereochemistry about the new five-membered ring
in 4 was determined from NOESY experiments (Figure
3) and was consistent with threo stereochemistry previ-
Compound 8 is apparently formed by ether linkage
of two units of threo-anethol glycol. Significant upfield
shifts were observed in the 13C resonances for C-7 and
C-8′ (∆δ +0.21 ppm and +0.10 ppm, respectively) of 8
following a D2O shake, indicating that these carbons
bear -OH groups (the upfield shift is a consequence of
secondary isotope effects following replacement of an

990 J ournal of Natural Products, 1998, Vol. 61, No. 8
Ta ble 3. 13C and1H Assignments for Compounds 8 and 9
Sy and Brown
Exp er im en ta l Section
δ
13C
δ 1Ha
Gen er a l E xp er im en t a l P r oced u r es. Chemical
shifts are expressed in ppm (δ) relative to TMS as
internal standard. All NMR experiments were run on
a Bruker DRX 500 instrument. HSQC and HMBC
spectra were recorded with 1024 data points in F2 and
256 data points in F1. High-resolution MS were re-
corded in EI mode at 70 e.v. on a Finnigan-MAT 95 MS
spectrometer. IR spectra were recorded in CHCl3 on a
BIO-RAD FT S-7 IR spectrometer. Column chromatog-
raphy was performed using silica gel 60-200 µm
(Merck). HPLC separations were performed using a
Varian chromatograph equipped with RI star 9040 and
UV 9050 detectors and a Intersil PREP-SIL 20 mm ×
25 cm column, flow rate 8 mL/min.
P la n t Ma ter ia l. Leaf tissue of I. verum was obtained
from the South China Botanical Garden (plant material
originally collected in Guangxi province by the Guangxi
Institute of Botany). A voucher specimen (Hao Gang103)
has been deposited in the University of Hong Kong
Herbarium (HKU).
atom
8
9
8
9
1
159.1
113.7
127.7
133.0
74.8
159.6
113.9
128.3
131.3
84.2
2/6
3/5
6.88 (d, 8.7)
7.27 (d, 8.7)
6.89 (d, 8.7)
7.33 (d, 8.7)
4
7
8
9
4.82 (d, 4.1)
3.62 (m)
0.84 (d, 6.4)
4.27 (d, 9.0)
3.72 (dq, 9.0, 6.3)
1.00 (d, 6.3)
78.3
15.8
76.9
17.3
1′
159.5
113.8
128.7
131.8
86.9
159.6
113.9
128.3
131.3
84.2
76.9
17.3
55.3
55.3
2′/6′
3′/5′
4′
7′
8′
6.87 (d, 8.7)
7.20 (d, 8.7)
6.89 (d, 8.7)
7.33 (d, 8.7)
4.06 (d, 8.4)
3.82 (m)
0.91 (d, 6.4)
3.81 (s)
4.27 (d, 9.0)
3.72 (dq, 9.0, 6.3)
1.00 (d, 6.3)
3.81 (s)
71.8
18.3
9′
1-OMe
1′-OMe
55.29
55.27
3.80 (s)
3.81 (s)
a
Multiplicity and coupling constants (Hz) indicated in paren-
theses.
-OH group by an -OD group10). Consequently, the
ether linkage in compound 8 is between oxygenated
carbons C-7′ and C-8. The value of the 1H coupling
constant for H-7/H-8 (J 7,8 ) 4.1 Hz) suggested erythro
stereochemistry for this half of the lignan, while that
for H-7′/H-8′ (8.4 Hz) suggested threo stereochemistry.
We propose that 8 is formed by SN2-type attack of the
7′-OH group of one molecule of threo-anethole glycol at
the 8-position of a second such molecule with consequent
inversion of configuration at the 8-position accompany-
ing formation of the 7′-O-8 bond. The 7-O-8′ lignan
skeleton of 8 apparently represents a new structrual
class.11
Extr a ction a n d Isola tion . The fresh sample (1.2
kg) was ground to a fine powder under liquid N2 in order
to ensure complete rupture of plant cell walls and
liberation of intracellular contents and then extracted
with CH2Cl2 over several days. The organic extract was
then dried and evaporated under reduced pressure to
yield a dark green oil (26.5 g; 2.2% w/w). Compounds
1-14 were isolated by column chromatography using
hexane and ethyl acetate (TLC plates used to monitor
the column were visualized using p-anisaldehyde). In
most cases, further purification was required by HPLC,
using ethyl acetate/hexane: 1a (161 mg); 1b (59 mg); 2
(16 mg); 3 (26 mg); 4 (23 mg); 5 (87 mg); 6 (58 mg); 7
(51 mg); 8 (567 mg); 9 (16 mg); 10 (12 mg); 11 (24 mg);
12 (6 mg); 13 (540 mg); 14 (15 mg); trans-anethole (1.28
g); (4-hydroxyphenyl)ethanol (24 mg); anisyl alcohol (75
mg); p-anisaldehyde (83 mg); p-anisic acid (26 mg).
th r eo-An eth ole glycol (1a ): oil; [R]D ) +7.7° (c 2.22,
CHCl3); IR (CHCl3) νmax 3420 (br), 3011, 2970, 2932,
The 1,4-dioxane lignan 9 demonstrated only nine
carbon resonances in the 13C NMR, indicating a sym-
metry element in the structure of this dimer. The
coupling constant between H-7/H-8 (and H-7′/H-8′) in
1H NMR (J ) 9.0 Hz) was indicative of a trans diaxial
relationship between these protons. We propose that
9 is formed from 8 by a second attack of the 8′-OH group
at the 7-center with an accompanying second inversion
at the 7-position. NOESY spectra for 9 (Figure 3)
demonstrated the expected “threo” stereochemistry for
each biogenetic phenylpropanoid moiety and a correla-
tion across the oxygen bridge (H7 f H8′) provided
evidence for the proposed double inversion of absolute
stereochemistry in one of the biogenetic phenylpro-
panoid units. Zero optical rotation was recorded for
compound 9, which was consistent with the foregoing
proposals. Compound 9 is a representative of a second
new structural class of 7-O-8′.8-O-7′ lignans.11
1
2856, 1612, 1514, 1250 cm-1; H NMR and 13C NMR,
Tables 1 and 2; HREIMS m/z 182.0945 (calcd for
C10H14O3, ∆ -0.2 mmu) (10), 137 (100), 109 (30), 94 (15).
er yth r o-An eth ole glycol (1b) isolated as a mixture
with 1a : 1H NMR and 13C NMR, Tables 1 and 2.
Der ivatization of 1a with (S)-(+)-MTP Cl To For m
(R)-MTP A Ester s 1c-f. To a solution of threo-anethole
glycol 1a (19.4 mg) in pyridine (0.36 mL) was added (S)-
(+)-MTPCl (0.02 mL). The solution was allowed to
stand at room temperature for 13 h, and then N,N-
diisopropylethylamine (0.02 mL) was added and the
mixture allowed to stand for 10 min. Solvent was
evaporated, and the products were separated by HPLC
in 15% ethyl acetate/hexane yielding compounds 1c-f.
Com p ou n d 1c: tR 21.5 min (23.7% of total reaction
product); 1H NMR (CDCl3) δ 7.49 (2H, m, H-4′/8′), 7.37
(3H, m, H-5′-7′), 7.27 (2H, d, J ) 8.0 Hz, H-3/5), 6.90
(2H, d, J ) 7.7 Hz, H-2/6), 5.31 (1H, dq, J ) 7.3, 6.3
Hz, H-8), 4.62 (1H, dd, J ) 7.3, 4.2 Hz, H-7), 3.82 (3H,
s, 1-OMe), 3.54 (3H, q, J ) 1.0 Hz, 2′-OMe), 2.17 (1H,
d, J ) 4.3 Hz, 7-OH), 1.12 (3H, d, J ) 6.3 Hz, H-9).
Com p ou n d 1d : tR 24.8 min (47.5% of total reaction
product); 1H NMR (CDCl3) δ 7.53 (2H, m, H-4′/8′), 7.40
(3H, m, H-5′-7′), 7.21 (2H, d, J ) 8.0 Hz, H-3/5), 6.85
Two other simple novel phenylpropanoids were also
isolated from the extract. Compound 10 is the acetate
of the known compound p-coumaryl alcohol 11 (com-
pound 11 was also present in the extract and was
identified from its NMR spectrum12); compound 12
incorporates a 3-hydroxyl group. Compound 13 is a
known lignan13,14 belonging to the well-established
furan class.11
Known compounds from the extract which were
identified from their 1D-NMR spectra included trans-
anethole,15,16 (4-hydroxyphenyl)ethanol,17 anisyl alco-
hol,18 p-anisaldehyde,19 and p-anisic acid.20

Phenylpropanoids and Neolignans from Illicium verum
J ournal of Natural Products, 1998, Vol. 61, No. 8 991
(2H, d, J ) 8.7 Hz, H-2/6), 5.29 (1H, dq, J ) 7.5, 6.4
Hz, H-8), 4.57 (1H, dd, J ) 7.5, 3.4 Hz, H-7), 3.80 (3H,
s, 1-OMe), 3.57 (3H, q, J ) 1.1 Hz, 2′-OMe), 2.11 (1H,
d, J ) 3.4 Hz, 7-OH), 1.19 (3H, d, J ) 6.4 Hz, H-9).
(3H, s, 1′-OMe), 3.79 (3H, s, 1-OMe), 3.42 (3H, s, 2′′-
OMe), 1.17 (3H, d, J ) 6.4 Hz, H-9).
Com p ou n d 3b: tR 32.2 min (48.3% of total reaction
1
product); H NMR (CDCl3) δ 7.95 (2H, d, J ) 8.9 Hz,
Com p ou n d 1e: tR 32.4 min (18.4% of total reaction
product); 1H NMR (CDCl3) δ 7.42 (2H, m, H-4′/8′), 7.38
(3H, m, H-5′-7′), 7.29 (2H, d, J ) 8.7 Hz, H-3/5), 6.89
(2H, d, J ) 8.7 Hz, H-2/6), 5.63 (1H, d, J ) 8.1 Hz, H-7),
4.07 (1H, m, H-8), 3.82 (3H, s, 1-OMe), 3.44 (3H, q, J )
0.7 Hz, 2′-OMe), 1.90 (1H, d, J ) 3.7 Hz, 8-OH), 1.00
(3H, d, J ) 6.4 Hz, H-9).
H-3′/5′), 7.42 (2H, d, J ) 7.8 Hz, H-4′′/8′′), 7.30 (2H, d,
J ) 8.7 Hz, H-3/5), 7.27 (1H, t, J ) 7.8 Hz, H-6′′), 7.15
(2H, t, J ) 7.8 Hz, H-5′′/7′′), 6.90 (2H, d, J ) 8.9 Hz,
H-2′/6′), 6.83 (2H, d, J ) 8.7 Hz, H-2/6), 5.87 (1H, d, J
) 7.7 Hz, H-7), 5.67 (1H, dq, J ) 7.7, 6.5 Hz, H-8), 3.86
(3H, s, 4′-OMe), 3.77 (3H, s, 1-OMe), 3.46 (3H, d, J )
0.7 Hz, 2′′-OMe), 1.24 (3H, d, J ) 6.5 Hz, H-9).
Der iva tiza tion of 3 w ith (R)-(-)-MTP Cl To F or m
(S)-MTP A Ester s 3c a n d 3d . The same procedure was
adopted as for 3 with (S)-(+)-MTPCl. Chromatographic
data for 3c were identical with 3a within 0.1 min (2%
peak integral). NMR data for 3c were identical to 3a
within 0.01 ppm. Chromatographic data for 3d were
identical with 3b within 0.1 min (2% peak integral).
NMR data for 3d were identical to 3b within 0.01 ppm.
Com p ou n d 1f: tR 35.4 min (10.4% of total reaction
product); H NMR (CDCl3) δ 7.41-7.34 (5H, m, H-4′-
8′), 7.15 (2H, d, J ) 8.7 Hz, H-3/5), 6.84 (2H, d, J ) 8.7
Hz, H-2/6), 5.58 (1H, d, J ) 8.1 Hz, H-7), 4.09 (1H, m,
H-8), 3.81 (3H, s, 1-OMe), 3.53 (3H, q, J ) 1.0 Hz, 2′-
OMe), 2.05 (1H, d, J ) 2.5 Hz, 8-OH), 1.05 (3H, d, J )
6.4 Hz, H-9).
1
Der iva t iza t ion of 1a w it h (R)-(-)-MTP Cl To
F or m (S)-MTP A Ester s 1g-j (1g Is Mir r or Im a ge
of 1c, 1h Is Mir r or Im a ge of 1d , 1i Is Mir r or Im a ge
of 1e, 1j Is Mir r or Im a ge of 1f). The same experi-
mental procedure was adopted as for (S)-(+)-MTPCl.
Chromatographic data were identical to within 0.1 min
(2% peak area) for 1g and 1c. NMR data for 1g were
identical to within 0.01 ppm with 1c (except 7-OH).
Chromatographic data were identical to within 0.1 min
(2% peak area) for 1h and 1d . NMR data for 1h were
identical within 0.01 ppm with 1d (except 7-OH).
Chromatographic data were identical to within 0.1 min
(2% peak area) for 1i and 1e. NMR data for 1i were
identical within 0.01 ppm with 1e (except 8-OH).
Chromatographic data were identical to within 0.1 min
(2% peak area) for 1j and 1f. NMR data for 1j were
identical within 0.01 ppm with 1f (except 8-OH).
Ver im ol C (4): oil; [R]D +2.1° (c 0.08, CHCl3); IR
(CHCl3) νmax 3013, 2961, 2934, 2839, 1614, 1516, 1248
cm-1; 1H NMR and 13C NMR, Tables 1 and 2; HREIMS
m/z 300.1357 (5) (calcd for C18H20O4, ∆ 0.5 mmu), 256
(10), 227 (50), 164 (100), 135 (30), 120 (45).
Ver im ol D (5): oil; [R]D -1.5° (c 0.58, CHCl3); IR
(CHCl3) νmax 3393 (br), 3009, 2966, 2936, 2839, 1612,
1514, 1248 cm-1; 1H NMR and 13C NMR, Tables 1 and
2; HREIMS m/z 302.1508 (5) (calcd for C18H22O4, ∆ 1.0
mmu), 301 (30), 255 (30), 240 (100), 225 (55), 165 (90),
137 (100), 119 (60).
Ver im ol E (6): oil; [R]D +7.0° (c 0.43, CHCl3); IR
(CHCl3) νmax 3609, 3420 (br), 3011, 2970, 2936, 2840,
1
1612, 1514, 1250 cm-1; H NMR and 13C NMR, Tables
1 and 2; HREIMS m/z 302.1511 (35) (calcd for C18H22O4,
∆ 0.7 mmu) (30), 301 (100), 284 (35), 137 (100).
8-(4-Meth oxyben oloyl)a n eth ole glycol, ver im ol A
Der iva tiza tion of 6 w ith 2,2-Dim eth oxyp r op a n e.
Compound 6 (20.2 mg) was dissolved in benzene (3 mL)
and 2,2-dimethoxypropane (0.16 mL) added with a trace
of p-toluenesulfonic acid. The mixture was stirred
under reflux for 90 min and 0.32 mg K2CO3 added and
then stirred for a further 4 h at room temperature. The
mixture was extracted with CH2Cl2 and dried (MgSO4).
Purification of the crude product yielded 6a (2.1 mg).
(2): oil; IR (CHCl3) νmax 3400 (br), 3013, 2936, 2841,
1
1707, 1607, 1514, 1254, 1169 cm-1; H NMR and 13C
NMR, Tables 1 and 2; HREIMS m/z 255 (10), 227 (20),
165 (30), 148 (35), 135.0444 (calcd for C8H7O2, ∆ 0.2
mmu, i.e., MeO(C6H4)CO+) (100).
7-(4-Meth oxyben zoloyl)a n eth ole glycol, ver im ol
B (3): oil; IR (CHCl3) νmax 3612, 3443 (br), 3013, 2974,
1
2928, 1713, 1607, 1514, 1252 cm-1; H NMR and 13C
1
Com p ou n d 6a : H NMR (CDCl3) δ 7.00 (2H, d, J )
NMR, Tables 1 and 2; HREIMS m/z 272 (12) [M+
-
8.7 Hz, H-2′/6′), 6.85 (2H, br d, H-2/6), 6.71 (2H, d, J )
8.7 Hz, H-3/5), 6.68 (2H, d, J ) 8.7 Hz, H-3′/6′), 4.87
(1H, d, J ) 10.5 Hz, H-7′), 4.29 (1H, dq, J ) 10.5, 6.0
Hz, H-8), 3.74 (3H, s, 1-OMe), 3.71 (3H, s, 1′-OMe), 2.46
(1H, t, J ) 10.5 Hz, H-7), 1.71 (3H, s, H-2′′), 1.56 (3H,
s, H-3′′), 1.02 (3H, d, J ) 6.0 Hz, H-9); 13C NMR (CDCl3)
δ 158.8 C (C-1′), 158.2 (C-1), 132.7 C (C-4′), 130.5 C (C-
4), 129.5 CH × 2 (br) (C-3/5), 128.3 CH × 2 (C-3′/5′),
113.8 CH × 2 (C-2/6), 113.3 CH × 2 (C-2′/6′) 98.7 C (C-
1′′), 76.9 CH (C-7′), 70.0 CH (C-8), 55.5 CH (C-7), 55.15
CH3 (1′-OMe), 55.11 CH3 (1-OMe), 30.3 CH3 (C-3′′), 20.1
CH3 (C-9), 19.9 CH3 (C-2′′).
C2H4O], 227 (8), 148 (10), 135.0444 (calcd for C8H7O2,
∆ 0.2 mmu, i.e., MeO(C6H4)CO+) (100).
Der iva tiza tion of 3 w ith (S)-(+)-MTP Cl To F or m
(R)-MTP A Ester s 3a a n d 3b. To a solution of 3 (15.0
mg) in pyridine (0.16 mL) was added (S)-(+)-MTPCl
(0.016 mL). The solution was allowed to stand at room
temperature for 13 h, and then N,N-diisopropylethy-
lamine (0.016 mL) was added and the mixture allowed
to stand for 10 min. The solvent was evaporated to yield
a crude product that was purified by HPLC in 15% ethyl
acetate/hexane, yielding compounds 3a and 3b.
1
Com p ou n d 3a : tR 29.1 min (51.7% of total reaction
Com p ou n d 6b: H NMR (CDCl3) δ 7.43 (4H, d, J )
1
product); H NMR (CDCl3) δ 7.97 (2H, d, J ) 8.8 Hz,
8.8 Hz, H-3/3′/5/5′), 6.93 (2H, s, H-7/7′), 6.88 (4H, d, J
) 8.8 Hz, H-2/2′/6/6′), 3.83 (6H, s, 1-OMe, 1′-OMe);13C
NMR (CDCl3) δ 150.9 C × 2 (C-1/1′), 130.5 C × 2 (C-4/
4′), 127.4 CH × 4 (C-3/3′/5/5′), 126.2 CH × 2 (C-7/7′),
114.1 CH × 4 (C-2/2′/6/6′), 55.3 CH3 × 2 (1-OMe/1′-
OMe).
H-3′/5′), 7.38 (2H, d, J ) 8.0 Hz, H-4′′/8′′), 7.34 (2H, d,
J ) 8.6 Hz, H-3/5), 7.28 (1H, t, J ) 8.0 Hz, H-6′′), 7.16
(2H, t, J ) 8.0 Hz, H-5′′/7′′), 6.90 (2H, d, J ) 8.8 Hz,
H-2′/6′), 6.86 (2H, d, J ) 8.6 Hz, H-2/6), 5.91 (1H, d, J
) 7.8 Hz, H-7), 5.67 (1H, dq, J ) 7.8, 6.4 Hz, H-8), 3.86

992 J ournal of Natural Products, 1998, Vol. 61, No. 8
Sy and Brown
Ver im ol F (7): oil; [R]D +5.5° (c 0.52, CHCl3); IR
(CHCl3) νmax 3583, 3458 (br), 3011, 2974, 2936, 2847,
Ver im ol K (14): oil; 1H NMR (CDCl3) δ 9.69 (2H, br
s, 1′/3′-OH), 7.43 (5H, m, H-3-7), 7.31 (1H, t, J ) 8.3
Hz, H-5′), 6.46 (2H, d, J ) 8.3 Hz, H-4′/6′), 5.50 (2H, s,
H-1); 13C NMR (CDCl3) δ 169.5 C (C-7′), 161.0 C (C-1/
3), 136.8 CH (C-5′), 133.9 C (C-2), 129.4 CH (C-5), 129.1
CH (C-4/6), 128.8 CH (C-3/7), 108.3 CH (C-4′/6′), 100.1
C (C-2′), 68.3 CH2 (C-1); HREIMS m/z 244.0737 (15)
(calcd for C14H12O4, ∆ -0.2 mmu), 91 (100).
1
1609, 1510, 1250 cm-1; H NMR and 13C NMR, Tables
1 and 2; HREIMS m/z 272.1414 (2) (calcd for C17H20O3,
∆ -0.2 mmu), 227 (100), 212 (5).
Ver im ol G (8): oil; [R]D +1.6° (c 1.67, CHCl3); IR
(CHCl3) νmax 3620, 3420 (br), 3013, 2976, 2930, 2899,
1
1610, 1510, 1250 cm-1; H NMR and 13C NMR, Table
3; HREIMS m/z 301.1438 [M+ - C2H5O] (10) (calcd for
C18H21O4, ∆ 0.2 mmu), 165 (35), 148 (100), 137 (95), 121
(20).
Ack n ow led gm en t. We thank Dr. Richard Saunders
of the Department of Ecology and Biodiversity for
identifying the sample of I. verum and Dr. Hao Dang
for collecting the sample. This research was funded by
a CRCG grant for research into the chemotaxonomy of
the Illiciales.
Ver im ol H (9): oil; [R]D 0.0° (c 1.23, CHCl3); IR
(CHCl3) νmax 3007, 2932, 2857, 1612, 1516, 1464, 1250
1
cm-1; H NMR and 13C NMR, Table 3; HREIMS m/z
328.1670 (10) (calcd for C20H24O4, ∆ 0.4 mmu), 148 (100).
Ver im ol I (10): oil; 1H NMR (CDCl3) δ 7.33 (2H, d, J
) 8.7 Hz, H-3/5), 6.86 (2H, d, J ) 8.7 Hz, H-2/6), 6.60
(1H, d, J ) 15.9 Hz, H-7), 6.15 (1H, dt, J ) 15.9, 6.6
Hz, H-8), 4.70 (2H, d, J ) 6.6 Hz, H-9), 3.81 (3H, s,
1-OMe), 2.10 (3H, s, MeCO); 13C NMR (CDCl3) δ 170.9
C (CdO), 159.6 C (C-1), 134.1 CH (C-7), 129.0 C (C-4),
127.9 CH × 2 (C-3/5), 120.9 CH (C-8), 114.1 CH × 2
(C-2/6), 65.4 CH2 (C-9), 55.3 CH3 (1-OMe), 21.1 CH3
(MeCO).
Refer en ces a n d Notes
(1) Claus, E. P.; Tyler, V. E. Pharmacognosy, 5th ed.; Lea and
Febiger: Philadelphia, 1965.
(2) Small, E. Econ. Bot. 1996, 50, 337-339.
(3) Tardy, E. Bull. Soc. Chim. Fr. 1990, 1902.
(4) J ackson, R. W.; Short, W. F. J . Chem. Soc. 1937, 513-516.
(5) Okuyama, E.; Nakamura, T.; Yamazaki, M. Chem. Pharm. Bull.
1993, 41, 1670-1671.
(6) Wolf, R. B. J . Nat. Prod. 1986, 49, 156-158.
(7) Pelter, A.; Peverall, S.; Pitchford, A. Tetrahedron 1996, 52,
1085-1094.
(8) Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J . Am. Chem.
Soc. 1991, 113, 4092-4096.
(9) Gleye, C.; Laurens, A.; Hocquemiller, R.; Laprevote, O.; Serani,
L.; Cave´, A. Phytochemistry 1997, 44, 1541-1545.
(10) Christofides, J . C.; Davies, D. B. J . Am. Chem. Soc. 1983, 105,
5099-5105.
Ver im ol J (12): oil; IR (CHCl3) νmax 3419 (br), 3011,
1
2974, 1610, 1510, 1220 cm-1; H NMR (CDCl3) δ 6.91
(1H, d, J ) 8.3 Hz, H-5), 6.51 (1H, d, J ) 2.6 Hz, H-2),
6.41 (1H, dd, J ) 8.3, 2.6 Hz, H-6), 4.20 (1H, m, H-8),
3.77 (3H, s, 1-OMe), 2.82 (1H, dd, J ) 14.7, 2.6 Hz, H-7a)
2.69 (1H, dd, J ) 14.7, 7.2 Hz, H-7b), 1.26 (3H, d, J )
6.2 Hz, H-9); 13C NMR (CDCl3) δ 160.0 C (C-1), 156.7 C
(C-3), 132.1 CH (C-5), 117.5 C (C-4), 106.2 CH (C-6),
102.8 CH (C-2), 70.7 CH (C-8), 55.3 CH3 (1-OMe), 39.9
CH2 (C-7), 23.2 CH3 (C-9); HREIMS m/z 182.0945 (35)
(calcd for C10H14O3, ∆ -0.2 mmu), 164 (45), 137 (100).
Com p ou n d (13): oil; IR (CHCl3) νmax 3531, 3003,
2932, 2855, 1610, 1514, 1269 cm-1; 1H NMR (CDCl3) δ
6.79 (2H, d, J ) 7.9 Hz, H-6/6′), 6.58 (2H, dd, J ) 7.9,
1.9 Hz, H-5/5′), 6.49 (2H, d, J ) 1.9 Hz, H-3/3′), 3.91
(2H, dd, J ) 8.6, 6.6 Hz, H-9a/9a′), 3.82 (6H, s, 2-OMe,
2′-OMe), 3.56 (2H, dd, J ) 8.6, 5.3 Hz, H-9b/9b′), 2.58
(2H, dd, J ) 13.7, 7.7 Hz, H-7a/7a′); 2.52 (2H, dd, J )
13.7, 7.7 Hz, H-7b/7b′), 2.16 (2H, m, H-8/8′); 13C NMR
(CDCl3) δ 146.4 C (C-2/2′), 143.9 C (C-1/1′), 132.3 C (C-
4/4′), 121.4 CH (C-5/5′), 114.1 CH (C-6/6′), 111.1 CH (C-
3/3′) 73.3 CH2 (C-9/9′), 55.8 CH3 (2/2′-OMe), 46.5 CH
(C-8/8′) 39.2 CH2 (C-7/7′); HREIMS m/z 344.1619 (100)
(calcd for C20H24O5, ∆ 0.5 mmu), 165 (5), 148 (20), 138
(60).
(11) Whiting, D. A. Nat. Prod. Rep. 1985, 191-211.
(12) Daubresse, N.; Francesch, C.; Mhamdi, F.; Rolando, C. Synthesis
1994, 369-371.
(13) Fang, J .-M.; Hsu, K.-C.; Cheng, Y.-S. Phytochemistry, 1989, 28,
3553-3555.
(14) Pan, H.; Lundgren, L. N. Phytochemistry 1995, 39, 1423-1428.
(15) Mohan, R. S.; Whalen, D. L. J . Org. Chem. 1993 58, 2663-2669.
(16) Pouchert, C. J .; Behnke, J . Aldrich Library of 13C and 1H FT
NMR spectra; Aldrich Chemical Co.: Milwaukee, 1993; Vol. 2,
p 208A.
(17) Pouchert, C. J .; Behnke, J . Aldrich Library of 13C and 1H FT
NMR spectra; Aldrich Chemical Co.: Milwaukee, 1993; Vol. 2,
p 409A.
(18) Pouchert, C. J .; Behnke, J . Aldrich Library of 13C and 1H FT
NMR spectra; Aldrich Chemical Co.: Milwaukee, 1993; Vol. 2,
p 352B.
(19) Pouchert, C. J .; Behnke, J . Aldrich Library of 13C and 1H FT
NMR spectra; Aldrich Chemical Co.: Milwaukee, 1993; Vol. 2,
p 941A.
(20) Pouchert, C. J .; Behnke, J . Aldrich Library of 13C and 1H FT
NMR spectra; Aldrich Chemical Co.: Milwaukee, 1993; Vol. 2,
p 1079B.
NP9800553