Three novel constituents from Curculigo capitulata and revision of C-2 stereochemistry in nyasicoside

Article abstract of DOI:10.1021/np980364t

Continuing study of the constituents of the rhizomes of Curculigo capitulata provided three novel compounds, including two norlignan glucosides, curcapicycloside (2) and (1S,2R)-O-methylnyasicoside (3), and a phenanthrofuran, curcapital (9). The former two compounds were characterized as their tetra-O-methyl derivatives. Compound 2 possesses a glucosyl-fused skeleton with 1R,2R configuration. Biogenetic consideration led to a revision of the previously assigned 2S configuration of nyasicoside (1) to 2R, which was confirmed by NOE studies of the acetonide of its tetra-O-methyl derivative. The 2R configuration in tetra-O-methyl-1-O-methyl curculigine (7a) and isocurculigine (8a) was also established by chemical correlation of the former with (1R,2R)-tetra-O-methyl-1-O-methylnyasicoside (10a). Curcapital (9) represents the first natural product having a phenanthro[9,10,b]furan skeleton.

Full text of DOI:10.1021/np980364t

734
J . Nat. Prod. 1999, 62, 734-739
Th r ee Novel Con stitu en ts fr om Cu r cu ligo ca pitu la ta a n d Revision of C-2
Ster eoch em istr y in Nya sicosid e
Wen-Liang Chang,† Chung-Hsiung Chen, and Shoei-Sheng Lee*
School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan, Republic of China
Received August 17, 1998
Continuing study of the constituents of the rhizomes of Curculigo capitulata provided three novel
compounds, including two norlignan glucosides, curcapicycloside (2) and (1S,2R)-O-methylnyasicoside
(3), and a phenanthrofuran, curcapital (9). The former two compounds were characterized as their tetra-
O-methyl derivatives. Compound 2 possesses a glucosyl-fused skeleton with 1R,2R configuration.
Biogenetic consideration led to a revision of the previously assigned 2S configuration of nyasicoside (1)
to 2R, which was confirmed by NOE studies of the acetonide of its tetra-O-methyl derivative. The 2R
configuration in tetra-O-methyl-1-O-methyl curculigine (7a ) and isocurculigine (8a ) was also established
by chemical correlation of the former with (1R,2R)-tetra-O-methyl-1-O-methylnyasicoside (10a ). Curcapital
(9) represents the first natural product having a phenanthro[9,10,b]furan skeleton.
We have reported the isolation and structure character-
ization of a novel glucosyl-fused phenanthrene, curcapito-
side,1 and five acetylenic norlignan glucosides2 from the
rhizomes of Curculigo capitulata (Lour.) O. Kuntze (Ama-
ryllidaceae), alias C. recurvata. These acetylenic norlignan
glucosides, especially nyasicoside (1) and (+)-1-O-butyln-
yasicoside, displayed potent activity against ouabain-
induced arrhythmia.2 To further explore potential anti-
arrhythmic agents, the minor constituents of this plant
were exhaustively investigated. A combination of chro-
matographic techniques and chemical derivatization pro-
vided eight additional compounds (2a , 3a , 4-9) from the
H2O-soluble fraction of EtOH extract of the rhizomes.
Among these, curculigine (4), isocurculigine (5), 1-O-methyl
curculigine (7), and 1-O-methyl isocurculigine (8) were
isolated and characterized as their respective tetra-O-
methyl ethers (4a , 5a , 7a , 8a ). Compound 6 was character-
ized as 1-O-methylcurculigine peracetate.3 In the following,
we report the structure characterization of three novel
compounds, curcapicycloside (2), (1S,2R)-1-O-methylnya-
sicoside (3), and curcapital (9). In addition, the revision of
consistent with two catechol-like moieties, with the latter
being conjugated with a carbonyl function (δC 198.47, s).
That both C-3 and C-4 in each aryl group were methoxy-
lated was revealed by NOE difference studies (Figure 1).
Analysis of the signals of seven sugar protons suggested a
â-D-glucosyl unit with the anomeric proton at δ 4.84 (d, J
) 8.1 Hz). The COSY-45 spectrum also revealed the
coupling pattern of two oxygenated methine protons at δ
4.57 (1H, m) and 4.70 (1H, d, J ) 5.6 Hz), as well as two
methylene protons at δ 1.89 (1H, m) and 2.18 (1H, m), the
latter pair being further coupled to two methylene protons
at δ 3.09 (1H, m) and 3.19 (1H, m). Taking all these
chemical shifts and their coupling relationships into con-
sideration, one would arrive at the structure sequence of
Ar-C(1)H(OR)-C(2)H(OR′)-CH2-CH2-CO-Ar for 2a , thus
allowing the attachment of â-D-glucose moiety at the C-1
or C-2 position, similar to that in nyasicoside (1). However,
the 1H NMR spectrum of the peracetylated product, 2b,
revealed only three acetyl methyl singlets, in contrast with
five signals of tetra-O-methyl nyasicoside peracetate. This
would require a C-1/C-2 glucosyl-fused skeleton for 2a .
Comparison of the chemical shift of the corresponding
sugar proton between 2a and 2b revealed large shift
differences for H-3′′′ (δ 3.44 vs δ 5.20), H-4′′′ (δ 3.44 vs δ
4.96), and H-6′′′ (δ 3.77 and 3.89 vs δ 4.10 and 4.20), in
C-2 stereochemistry in nyasicoside (1) and related com-
pounds and the chemical confirmation of C-2 stereochem-
istry of 4a and 7a and their C-1 epimers are also reported.
Resu lts a n d Discu ssion
Curcapicycloside (2), being unstable during the final step
of purification, was isolated and characterized as its tetra-
O-methylated derivative, 2a . Compound 2a , a white amor-
phous solid, had a molecular formula of C27H35O11 (HR-
FABMS). The IR absorptions at 3400, 1665, 1590, and 1520
cm-1 indicated the presence of hydroxyl functions and an
1
aryl ketone moiety. The H NMR spectrum showed signals
for six aromatic protons in two ABX systems, and seven
sugar protons, both being corroborated by a COSY-45
spectrum, in addition to signals for six aliphatic protons
and four aryl methoxys (δ 3.95, 3.93, 3.90, and 3.88). Both
sets of ABX systems, one at δ 7.03 (d, J ) 1.6 Hz, H-2′),
6.87 (d, J ) 8.6 Hz, H-5′), and 7.03 (dd, J ) 8.6, 1.6, H-6′)
and the other at δ 7.50 (d, J ) 1.3 Hz, H-2′′), 6.92 (d, J )
8.4 Hz, H-5′′), and 7.62 (dd, J ) 1.3, 8.4 Hz, H-6′′), were
* To whom correspondence should be addressed: Tel.: 886-2-23916127.
Fax: 886-2-3919098. E-mail: shoeilee@ha.mc.ntu.edu.tw.
† Current address: School of Pharmacy, National Defense Medical
Center, Taipei 100, Taiwan, ROC.
10.1021/np980364t CCC: $18.00
© 1999 American Chemical Society and American Society of Pharmacognosy
Published on Web 05/07/1999

Constituents of Curculigo
J ournal of Natural Products, 1999, Vol. 62, No. 5 735
F igu r e 1. NOE’s of 2a .
Ta ble 1. 1H and 13C NMR Data (δ/ppm), and 2D NMR Data
for 2a (CDCl3 + CD3OD ) 4:1) and 1H NMR Data of 2b
(CDCl3)
F igu r e 2. Energy-minimized conformation of 2a .
H-2. This would require 1R and 2R stereochemistry in 2a ,
elucidated on the basis of the known stereochemistry of
the â-D-glucosyl unit. The larger NOE of H-2′′′ to H-2 (7.3%)
than that of H-1′′′ to H-1 (1.1%) also suggests a twisted
boat conformation for the dioxan moiety. This was sup-
ported by a computer-assisted modeling study4 of 2a that
afforded an energy-minimized conformation (Figure 2)
consistent with the NOE data. Analysis of HMBC (Table
1) and HMQC data by incorporating the NOE and COSY-
2a
2b
δC
δH mult. HMBC (J ) 8 Hz)
δH mult.
position mult.a
(J /Hz)b
correlated C (#)
(J /Hz)c
1
2
3
78.17 d
74.10 d
25.87 t
4.70 d (5.6) 3, 2, 1′, 2′, 6′, 2′′′ 4.64 d (4.4)
4.57 m
1.89 m,
1′
4.57 m
2.00 d (6.0),
2.33 m
2.18 m
4
33.33 t
3.09 m,
3, 5
3.10 m
3.19 m
5
198.47 s
130.76 s
1
45 correlations, furnished the complete H and 13C NMR
1′
2′
3′
4′
5′
6′
110.74 d 7.03 d (1.6) 1, 4′, 6′
7.91 d (1.5)
assignments (Table 1) for 2a . The MS revealed the base
fragment ions at m/z 165 (A), obtained via R-cleavage of
the aliphatic chain, and a characteristic fragment ion at
m/z 356 (B), obtained via a retro Diels-Alder-type frag-
mentation of the dioxan ring, both supporting the assigned
structure. To our knowledge, 2a represents the first natural
occurrence of a 1,5-diphenylpentanone-type norlignan gly-
coside. The trivial name for the parent compound of 2a ,
curcapicycloside (2), was made after its plant origin.
148.70 s
148.83 s
110.86 d 6.87 d (8.6) 1′, 3′
120.00 d 7.03 dd (8.6, 1, 2′
6.83 d (8.6)
6.98 dd (8.4, 1.5)
1.6)
1′′
2′′
3′′
4′′
5′′
6′′
129.64 s
109.91 d 7.50 d (1.3) 5, 3′′, 4′′, 6′′
7.48 d (1.6)
148.78 s
153.19 s
109.91 d 6.92 d (8.4) 1′′, 3′′
122.69 d 7.62 dd (8.4, 5, 2′′, 4′′
1.3)
6.86 d (8.5)
7.58 dd (8.5, 1.6)
Glc 1′′′ 95.58 d
4.84 d (8.1) 2′′′, 5′′′
4.85 d (8.5)
2′′′
72.22 d
3.64 dd (9.2, 2, 1′′′
3.71 dd (9.6, 8.5)
8.1)
3′′′
4′′′
5′′′
6′′′
77.32 d
70.42 d
74.29 d
61.28 t
3.44b
5.20 dd (9.6, 9.3)
4.96 dd (9.3, 9.3)
3.79 m
4.10 dd (12.7,
1.7)
4.20 dd (12.7, 4.8)
3.86 s, 3.87 s
3.44b
3.60 m
3.77 dd
4′′′
4′′′
(11.8, 4.9)
3.89b
On the basis of biogenetic point of view, the C-2 config-
uration of nyasicoside (1) might be the same (i.e., 2R) as
that in curcapicycloside (2). Previous elucidation of 1R,2S
configuration for 1 by Chifundera et al.5 was based on the
following points: (a) comparison of the CD curves between
1 and (1R)-phenylethanediol or ephedrine‚HCl to derive the
C-1 configuration, (b) the exciton coupling in the CD
spectrum of the 1,2-dibromobenzoate derivative to derive
C-2 configuration; and (c) the coupling constant of H-1 and
H-2 (J ) 8.5 Hz) of the acetonide derivative to establish
the cis relationship between H-1 and H-2. We further
confirmed the 1R configuration in 1 by observation of the
similar CD curve between the prepared tetra-O-methyl-
tetrahydronyasicoside (11) and the model compound adrena-
line, both showing a negative Cotton effect around 230 nm.
To examine the C-2 stereochemistry of 1, we prepared the
same acetonide derivative, tetra-O-methylnyasicol 1,2-
acetonide (12), which has identical physical data to those
reported,5 including the coupling constant of H-1 and H-2.
The NOE studies of 12 (Figure 3) revealed that the signals
of H-1 (δ 4.84) and H-2 (δ 3.96) were enhanced, respec-
tively, upon irradiation of each methyl frequency (δ 1.54,
and δ 1.57) of acetonide. Both signals of H-2′ and H-6′ were
enhanced upon irradiation of H-1 or H-2 frequency. From
a chemical model study, these results could be rationalized
only if H-1 and H-2 were trans oriented. These data
provided solid evidence for a trans relationship between
H-1 and H-2, instead of the reported cis. Based on this
OMe 55.60 q, 3.88 s, 3.90 s
55.70 q
55.50 q
3.92 s, 3.95 s
3.90 s, 3.92 s
(x2)
a
b
Multiplicities were obtained from DEPT experiments. Sig-
nals without multiplicity were assigned from COSY-45 or HMQC
spectra. c Three -OCOMe signals at 1.99 (2 Me, s) and 2.04 (1
Me, s).
contrast with small differences for H-1′′′ (δ 4.84 vs δ 4.85)
and H-2′′′ (δ 3.64 vs δ 3.71). This suggested ether linkage
between C-1 and C-2 of the sugar moiety with C-1 and C-2
of the aglycon to form a 1,4-dioxan skeleton for 2a , which
is consistent with a total ring and double-bond equivalent
of 11, including two catechols, one ketone, and one glucose
unit. Without consideration of stereochemistry, these data
would narrow the structure for 2a to two possibilities,
depending on alternative ways of fusion with glucose
unit: that is, C1-O-C1′′′/C2-O-C2′′′ or C1-O-C2′′′/C2-O-
C1′′′
.
An HMBC spectrum (Table 1) revealed a key coupling
of H-1 to C-2′′′, establishing C-2′′′ of the glucose fused to
C-1 of the aglycon. NOE studies of 2a (Figure 1) revealed
the enhancement of the H-1 signal (δ 4.70) upon irradiation
of H-1′′′ and that of the H-2 signal (δ 4.57) upon irradiation
of H-2′′′, thus confirming the C1-O-C2′′′/C2-O-C1′′′ link-
age. Incorporating the â-D-glucosyl unit, the common
glycone of nyasicoside, and related compounds from the
same plant established the trans relationship of H-1 and

736 J ournal of Natural Products, 1999, Vol. 62, No. 5
Chang et al.
in 4a ). To confirm the assigned 1R,2R stereochemistry
made by the exciton coupling of the benzoate derivatives,3
the stereochemistry at C-1 and C-2 of curculigine-type
norlignans was further elucidated by chemical correlation.
Hydration of tetra-O-methylnyasicoside (1a )6 catalyzed
with mercuric oxide in H2SO4-H2O7 yielded tetra-O-
methylisocurculigine (5a ) in addition to the expected tetra-
O-methylcurculigine (4a ) (Figure 4), a result indicating the
susceptible epimerization at the C-1 benzylic position under
acidic conditions. The same reaction performed on (1R,2R)-
tetra-O-methyl-1-O-methylnyasicoside (10a ) yielded the
desired product, 7a (CD and NMR data), in addition to a
mixture of 4a and 5a (Figure 4), confirming this suggestion.
This result provided solid support for the 1R,2R stereo-
chemistry of 1-O-methylcurculigine tetra-O-methyl ether
(7a ). As the CD curve of 8a was almost a counterpart of
7a , the 1S,2R stereochemistry of 8a was established
inasmuch as the chirality at the benzylic position generally
dominated the Cotton effect as that of C-2 in flavanones.8
Complementary support for the stereochemistry assign-
ment of 4a (1R,2R) and 5a (1S,2R) also comes from the
comparable coupling constant between H-1 and H-2 in 4a
(8.3 Hz) as compared with 7a (5.6 Hz), and in 5a (2.4 Hz)
as compared with 8a (2.9 Hz) (Table 2), a similar situation
being observed for C-1 epimers of 1-O-butylnyasicoside2
and 1-O-methylnyasicoside.
F igu r e 3. NOE’s of compound 12.
study, nyasicoside (1) was revised to have the same 1R,2R
stereochemistry as curcapicycloside (2), instead of the
previously reported 1R,2S configuration.
This revision for C-2 stereochemistry in 1 should be
applicable to other nyasicoside-related compounds, includ-
ing 1-O-methyl-, 1-O-butyl-, and 3′′-dehydroxy-nyasico-
sides.2 That is, they should all possess 2R configuration.
Compound 3a , [R]23 -74.3° (c 0.7, MeOH), has a
D
molecular formula of C28H36O11 as deduced from negative
HRFABMS, which is 56 amu more than that of (+)-(1R,2R)-
1-O-methyl nyasicoside (10).2 Except for the additional four
aryl methoxyl signals at δ 3.83 (3 × OMe) and 3.85, the
1H NMR spectrum of 3a is very similar to that of 10.
Further 1H NMR analysis of 3a and 10a , a tetra-O-
methylated derivative of 10, however, revealed differences
in chemical shifts and coupling constants for H-1, H-2, and
H-3, of which J 1,2 coupling in 3a is 4.2 Hz as compared
with 6.1 Hz in 10a , the former coupling being similar to
that in (-)-(1S,2R)-1-O-butylnyasicoside.2 The 13C NMR
spectrum of 3a is also very similar to that of 10 except for
the differences in signals of two aryl groups. The CD
spectrum of 3a is almost a mirror image of that of 10 with
1R configuration, suggesting 1S stereochemistry for 3a .
These data pooled together would establish the structure
of 3a to be a novel (-)-(1S,2R)-tetramethyl-1-O-methyln-
yasicoside, and the parent compound to be (-)-(1S,2R)-1-
O-methylnyasicoside (3).
This study characterized the structure of tetra-O-meth-
ylcurcapicycloside (2a ), which induced the revision of C-2
stereochemistry of nyasicoside-type norlignan glycosides.
Curculigine (4), a nyasicoside-derived 1,5-diphenylpen-
tanone-type norlignan glycoside, has been demonstrated
by the CD exciton coupling method3 to have the same 2R
stereochemistry as that in 1 and 2a . In view of their
biogenetic relationship, this consistency in C-2 stereochem-
istry among these lignan glycosides lends firm support for
this revision.
1
Having these pure C-1 epimers at hand, the H and 13C
NMR spectral data of 4a , 5a , 7a , and 8a , which were
assigned previously in a mixture stage,3 were examined
directly. The resulting assignments are listed in Tables 2
and 3.
Curcapital (9) was isolated from a MeOH-soluble fraction
as an orange amorphous solid. The molecular formula of 9
was deduced as C17H10O6 from HRFABMS. The UV ab-
sorptions at 221, 250, 276, 309, and 376 nm were similar
to those in curcapitoside peracetate,1 suggesting the pres-
ence of phenanthrene chromophore. It contained an aryl
formyl group as revealed by the presence of an IR absorp-
1
tion at 1630 cm-1, a H NMR signal at δ 9.64 (s), and a 13C
1
NMR signal at δ 179.70 (d). The H NMR (CD3OD) spectra
showed five singlets for aromatic protons at δ 7.40, 7.54,
7.73, 7.74, and 7.96, suggesting the presence of two pairs
of para aryl protons. This was partially corroborated by a
COSY-45 spectrum, which showed a long-range coupling
between the singlets at δ 7.74 (H-5) and 7.54 (H-8). NOE
studies (Figure 5) showed mutual enhancements between
both singlets at δ 7.73 (H-4) and 7.74 (H-5). Mutual
enhancements were also observed between the singlet at
δ 7.96 (H-11) and the singlet at δ 7.40 (H-1) as well as the
signal of aldehydic proton (δ 9.64). Pooling all these data
together one would derive the structure 2,3,6,7-tetrahy-
droxy-phenanthro[10,9-d]furan-2-carboxaldehyde for com-
pound 9.
Compounds 4 and 5 were found to be a 1:1 mixture of
curculigine and isocurculigine.3 Both compounds were
reported to be inseparable and were characterized as
mixture. We found that their tetra-O-methylated deriva-
tives (4a , 5a ) could be separated by reversed-phase pre-
parative HPLC. After Lobar RP18 column separation,
compounds 7 and 8 were found to be a 1:1 mixture of 1-O-
methylcurculigine and 1-O-methylisocurculigine as re-
The HMBC spectrum revealed couplings of H-11 (δ 7.96)
to carbons in the furan moiety, including C-9 (J 3), C-10,
and C-12 (J 2), and the aldehydic carbon (C-13, J 3), of which
C-9 (δ 153.51) and C-10 (δ 120.10) are further three-bond
coupled to H-8 and H-1, respectively, in the phenanthrene
moiety. These data confirmed the assigned structure for
9. Analysis of the 2D NMR spectra, HMQC, and HMBC
also allowed complete 13C NMR assignment for 9 as listed
in Table 4. To our knowledge, 9 represents the first natural
occurrence of phenanthro[10,9d]furan skeleton. The trivial
name curcapital is made for 9 after its plant origin and
structural character.
1
ported,3 based on H NMR spectral analysis. Although we
observed that they could be separated by HPLC (ODS),
decomposition occurred upon concentration of the eluents.
To overcome this problem, the phenolic groups were
protected by treating them with diazomethane to give tetra-
O-methylated derivatives (7a and 8a ), which were found
to be separable by reversed-phase preparative HPLC.
On the basis of biogenetic point of view, the C-1 and C-2
configuration of curculigine (4) might be the same (i.e.,
1R,2R) as that in nyasicoside (1). However, the CD curves
of both compounds are quite different, owing to the distinct
chromophores (i.e., phenylacetylene in 1 vs benzophenone

Constituents of Curculigo
J ournal of Natural Products, 1999, Vol. 62, No. 5 737
F igu r e 4. Hydration of tetra-O-methylnyasicoside and its 1-O-methyl derivative catalyzed by mercuric ion.
Ta ble 2. 1H NMR Data for Compounds 4a , 5a , 7a , and 8a (δ/ppm, J in Hz)a
position
4a b
5a b
7a c
8a c
1
4.40 d (8.3)
3.80 m
1.61 q (7.2)
2.92 m
4.78 d (2.4)
3.80 m
1.72 m
2.91 m
4.48 d (5.6)
4.02 m
4.64 d (2.9)
3.80 m
2
3
4
1.53 dd (5.4, 17.1) 1.93 dd (4.2, 17.1) 1.89 m
3.04 m
2.98 m
3.07 m
3.03 m
3.30 m
3.26 m
2′
5′
6′
2′′
5′′
6′′
6.86 d (1.6)
6.76 d (8.2)
6.83 dd (1.6, 8.2)
7.36 d (1.9)
6.80 d (8.6)
7.47 dd (8.6, 1.9)
6.92 d (1.4)
6.74 d (8.2)
6.81 dd (1.4, 8.2)
7.38 d (1.8)
6.81 d (8.4)
7.48 dd (8.4, 1.8)
7.01 d (1.5)
6.90 d (8.2)
6.93 dd (1.5, 8.2)
6.81 d (1.9)
6.96 d (8.4)
7.59 dd (1.9, 8.4)
6.98 d (1.5)
6.89 d (8.2)
6.89 dd (1.5, 8.2)
6.82 d (1.9)
6.96 d (8.4)
7.61 dd (8.4, 1.9)
Glc
1′′′
2′′′-5′′′
6′′′
4.41 d (7.8)
3.30-3.39
4.38 d (7.6)
3.28-3.39
4.47 d (8.0)
3.30-3.39
4.42 d (7.7)
3.30-3.39
3.67 dd (4.6, 12.1) 3.80 3.68 dd (4.6, 12.1) 3.80 3.69 dd (4.9, 11.8) 3.86 dd (1.4, 11.8) 3.69 dd (4.9, 11.8) 3.86 dd (1.4, 11.8)
Ar-OMe 3.78, 3.82, 3.84, 3.94 s 3.77, 3.81, 3.82, 3.86 s 3.80 (x 2), 3.84, 3.87 s
3.80, 3.81, 3.84, 3.88 s
3.32 s
1-OMe
3.26 s
a
b
Signals without multiplicity were assigned from COSY-45 or HMQC spectra. In CDCl3-CD3OD (4:1). c In CD3OD.
Ta ble 3. 13C NMR Assignments for Compounds 4a , 5a , 7a ,
and 8a (δ/ppm)a
position
4a a
5a a
7a c
8a c
1
77.02 d
75.02 d
86.15 d
87.00 d
2
85.78 d
84.79 d
81.83 d
84.65 d
3
26.94 t
25.11 t
26.32 t
24.86 t
4
33.68 t
34.31 t
34.80 t
35.36 t
5
1′
2′
3′
4′
5′
6′
200.14 s
132.67 s
110.39 d
149.09 s
149.23 s
111.39 d
120.34 d
129.94 s
110.34 d
149.08 s
153.60 s
110.53 d
123.34 d
200.45 s
132.98 s
110.42 d
148.81 s
149.09 s
111.00 d
119.43 d
129.92 s
110.34 d
148.36 s
153.62 s
110.58 d
123.41 d
201.60 s
132.16 s
112.46 d
150.20 s
150.34 s
113.12 d
121.84 d
131.20 s
111.73 d
150.11 s
155.00 s
111.73 d
124.37 d
201.94 s
132.90 s
112.18 d
150.32 s
150.40 s
112.66 d
120.91 d
131.18 s
111.69 d
149.85 s
154.98 s
111.75 d
124.40 d
F igu r e 5. NOE’s (italics, %) of 9 (CD3OD)
Ta ble 4. 1H and 13C NMR Data (δ/ppm) and HMBC Data for 9
in CD3OD
1′′
2′′
3′′
4′′
5′′
6′′
Glc
1′′′
2′′′
3′′′
4′′′
5′′′
6′′′
Ar-
OMe
δH
COSY-45
HMBC
position (mult.) corr. H (#) δC (mult.)a (J ) 8.0 Hz) corr. C (#)
1
2
3
4
4a
4b
5
6
7
8
8a
9
10
10a
11
12
7.40 s
7.73 s
7.74 s
7.54 s
11
8
109.34 d
147.13 s
147.31 s
109.24 d
123.57 s
127.90 s
109.19 d
149.17 s
146.71 s
106.52 d
115.54 s
153.51 s
120.10 s
121.05 s
120.30 d
152.85 s
179.70 d
2, 3, 4a, 10
103.37 d
73.86 d
76.78 d
70.07 d
76.78 d
61.58 t
103.86 d
73.92 d
76.48 d
70.11 d
76.61 d
61.59 t
104.34 d
75.33 d
78.00 d
71.76 d
78.06 d
62.91 t
105.40 d
75.34 d
77.88 d
71.82 d
78.16 d
63.00 t
2, 3, 4a, 4b, 10a
4a, 6, 7, 8a, 9
4b, 6, 7, 9
8, 11
5
55.96, 56.00, 55.94, 55.97, 56.40 (× 2), 56.40, 56.50
56.02,
56.02,
56.12 q
56.60
(× 3) q
57.79 q
56.12 q
(× 2) q
1-OMe
57.31 q
a
b
Multiplicities were obtained from DEPT experiments. In
CDCl3-CD3OD (4:1) c In CD3OD.
7.96 s
9.64 s
1, 5, 13
11
9, 10, 12, 13
12
Exp er im en ta l Section
13
Gen er al Exper im en tal P r ocedu r es. Perkin-Elmer 1760-X
infrared FT spectrometer (KBr); Hitachi 2000 UV (MeOH);
J ASCO J -710 spectropolarimeter (MeOH); J EOL J MX-HX110
mass spectrometer; Bruker AMX-400 NMR spectrometer in
MeOH-d4 (δH 3.30, δC 49.0) or CDCl3 (δH 7.24, δC 77.0) using
Bruker’s standard pulse programs; in the HMQC and HMBC
a
Multiplicities were obtained from DEPT experiments.
experiments, ∆ ) 1 s and J ) 140, 8 Hz, respectively, the
correlation maps consisted of 512 × 1 K data points per
spectrum, each composed of 16 to 64 transients.
P la n t Ma t er ia l. The rhizomes of Curculigo capitulata

738 J ournal of Natural Products, 1999, Vol. 62, No. 5
Chang et al.
(Lour.) O. Kuntze for this study were re-collected in J anuary
1995, from the suburban mountain of Wen-Xi, Taipei, Taiwan.
A voucher specimen has been deposited in the School of
Pharmacy, National Taiwan University.
Extr a ction a n d Isola tion . The ground, dry powders of the
rhizomes (1.1 kg) were percolated with 95% EtOH (7 L × 5).
The EtOH extract (110 g) was partitioned between H2O (1 L)
and CHCl3 (1 L × 3) to give a CHCl3-soluble fraction (8.10 g).
The aqueous layer, after removal of the residual CHCl3 in
vacuo, was passed through an Amberlite XAD-2 column (2 kg),
washed with H2O, and eluted with 30% to 100% MeOH in H2O,
to give fractions of 30% MeOH (35.01 g), 50% MeOH (3.60 g),
and MeOH (0.98 g).
Part of the 30% MeOH fraction (4.96 g) was further
separated on a Lobar RP8 column (B type, Merck), eluted with
MeOH-H2O (3:7) to give six fractions. Fraction 4 (1.31 g) was
pure nyasicoside (1).2,5,6 Fraction 2 (360 mg out of 952 mg),
containing the mixture of curculigine (4) and isocurculigine
(5),3 was dissolved in MeOH and was O-methylated by reacting
with freshly prepared ethereal CH2N2 at 4 °C for 3 days. The
residue (394 mg) obtained after evaporating the organic
solvents was separated on a Lobar RP8 column (B type, 50%
MeOH in H2O) and subsequently on a preparative C18 HPLC
column (32% MeOH in H2O) to give curculigine tetra-O-methyl
ether (4a , 30 mg) and isocurculigine tetra-O-methyl ether (5a ,
20 mg).
(1S)-Tetr a m eth yl-1-O-m eth yln ya sicosid e (3a ): amor-
phous powder; Rf
0.33 [MeOH-CHCl3 (1:9)]; [R]23 -74.3° (c
D
0.7, MeOH); UV λmax (log ꢀ) 223 (sh, 4.44), 257 (4.36), 285 (3.89),
298 (sh, 3.72) nm; IR νmax 3400 (br s), 2940, 1510, 1460, 1410,
1260, 1240, 1140, 1080, 1020, 900, 860, 820, 760, 620 cm-1
;
CD (1.82 × 10-5 M) (∆ꢀ) 315 (0), 283 (-2.06), 252 (-6.62), 234
(-1.10), 224 (-6.18), 211 (-15.96) nm; 1H NMR (CDCl3) δ 6.96
(1H, dd, J ) 1.7, 8.4 Hz, H-6′′), 6.90 (1H, d, J ) 1.4 Hz, H-2′),
6.88 (1H, d, J ) 1.7 Hz, H-2′′), 6.87 (1H, dd, J ) 1.4, 8.6 Hz,
H-6′), 6.82 (1H, d, J ) 8.6 Hz, H-5′), 6.74 (1H, d, J ) 8.4 Hz,
H-5′′), 4.52 (1H, d, J ) 7.7 Hz, Glc H-1), 4.38 (1H, d, J ) 4.2
Hz, H-1), 4.05 (1H, m, H-2), 3.85 (3H, s, Ar-OMe), 3.83 (9H,
s, Ar-OMe × 3), 3.80 (1H, m) and 3.70 (1H, m) (Glc H-6), 3.28
(3H, s, 1-OMe), 2.74 (1H, dd, J ) 7.6, 17.0 Hz) and 2.53 (1H,
dd, J ) 5.3, 17.0 Hz) (H-3); 13C NMR (CDCl3) δ 149.30 (s, C-4′′),
148.90 (s, C-4′ and C-3′′), 148.62 (s, C-3′), 129.68 (s, C-1′),
124.69 (d, C-6′′), 120.41 (d, C-6′), 114.40 (d, C-2′), 114.31 (s,
C-1′′), 111.05 (d, C-5′′), 110.92 (d, C-2′′), 110.70 (d, C-5′), 102.68
(d, Glc C-1), 84.84 (s, C-4), 84.31 (d, C-1), 82.55 (s, C-5), 79.93
(d, C-2), 76.22 (d, Glc C-5), 75.61 (d, Glc C-3), 73.11 (d, Glc
C-2), 70.13 (d, Glc C-4), 62.19 (t, Glc C-6), 57.24 (q, 1-OMe),
55.98 (q), 55.90 (2C, q) and 55.85 (q) (4 × Ar-OMe), 21.89 (t,
C-3); FABMS (pos.) m/z [M + Na]+ 571 (100), [M]+ 548 (4),
413 (24), 391 (16), 181 (25), 176 (41), 91 (55), 77 (55), 69 (75),
55 (100); HRFABMS (pos.) m/z [M + H]+ 549.2438 (calcd for
C
28H37O11 549.2335).
Part of fraction 5 (380 mg out of 960 mg) was separated on
a preparative HPLC column (C18, 32% MeOH in H2O) to give
two subfractions. The compounds in the first eluted subfrac-
tion, however, were decomposed during concentration. Upon
evaporation, the residue of the second subfraction was per-
acetylated with Ac2O-py. After general workup, the acetylated
products were separated on a Si gel column (230-400 mesh,
1% MeOH in CHCl3) to give curcapitoside peracetate (16 mg)1
and 1-O-methylcurculigine peracetate (6, 40 mg).3 Another
portion of fraction 5 (360 mg) was dissolved in MeOH and
O-methylated by reacting with freshly prepared ethereal
CH2N2 at 4 °C for 3 days. The residue (390 mg) obtained after
evaporating the organic solvents was separated on a Lobar
RP8 column (55% MeOH in H2O) to give four subfractions.
Subfractions 1 (140 mg) and 4 (30 mg) gave compound 2a (24
mg) and tetramethylnyasicoside (1a )6 (60 mg) (subfraction 1),
and 3a (8 mg) (subfraction 4) after separation by Si gel column
chromatography (230-400 mesh, 1% MeOH in CHCl3). Sub-
fraction 2 (48 mg), shown to be a mixture of tetramethyl-1-O-
methyl derivatives of curculigine and isocurculigine (7a , 8a )3
Tetr a -O-m eth ylcu r cu ligin e (4a ): amorphous powder; Rf
0.19 [MeOH-CHCl3 (1:9)]; [R]20D -21.7° [c 0.6, CHCl3-MeOH
(1:1)]; IR νmax 3400 (br s), 2950, 1665, 1590, 1510, 1420, 1280,
1160, 1080, 1020 cm-1; UV λmax (log ꢀ) 228 (4.40), 274 (4.12),
301 (3.88) nm; CD (c 1.81 × 10-5 M) (∆ꢀ) 326 (+0.19), 314 (0),
310 (+0.05), 302 (+0.06), 295 (-0.09), 286 (+0.15), 271 (-0.39),
266 (-0.34), 259 (-0.53), 246 (-0.17), 233 (-1.34), 209 (+0.44);
1H and 13C NMR, see Tables 2 and 3; FABMS (neg.) m/z (rel
int.) [M - H]- 551 (4), 537 (3), 377 (4), 303 (4), 287 (13), 229
(7), 197 (33), 179 (8), 153 (21), 139 (20), 107 (100).
Tetr a -O-m eth ylisocu r cu ligin e (5a ): amorphous powder;
Rf 0.19 [MeOH-CHCl3 (1:9)]; [R]20D -6.0° [c 0.5, CHCl3-MeOH
(1:1)]; UV λmax (log ꢀ) 228 (4.33), 274 (4.05), 300 (3.81) nm; IR
ν
max 3400 (br s), 2950, 1665, 1590, 1510, 1420, 1280, 1020 cm-1
;
CD (c 1.81 × 10-5 M) (∆ꢀ) 322 (+0.37), 313 (+0.14), 308
(+0.23), 302(+0.09), 294 (+0.29), 275 (-0.28), 267 (-0.29), 252
(+0.15), 248 (+0.08), 240 (+0.49), 229 (-0.07), 208 (-2.65);
1H and 13C NMR, see Tables 2 and 3; FABMS (neg.) m/z (rel
int.) [M - H]- 551 (4), 537 (3), 377 (6), 303 (4), 287 (18), 229
(12), 197 (36), 179 (9), 153 (12), 139 (26), 107 (100), 105 (15).
1
by H and 13C NMR spectral analysis, was further separated
by successive chromatography on a Lobar RP8 column (55%
MeOH in H2O) and a preparative HPLC column (C18, 40%
MeOH in H2O) to give 7a (16 mg) and 8a (9 mg). Fraction 6
(780 mg) was subjected to a Lobar RP8 column (30% MeOH in
H2O) to give 3′′-dehydroxynyasicoside2 (280 mg) and 1-O-
methylnyasicoside2 (10, 130 mg).
The MeOH-eluted fraction (980 mg) of the initial Amberlite
XAD-2 column was subjected to a Lobar RP8 column (54%
MeOH in H2O) to give compound 9 (98 mg).
1-O-Meth ylcu r cu ligin e Tetr a-O-m eth yl Eth er (7a): amor-
phous powder; Rf 0.33 [MeOH-CHCl3 (1:9)]; [R]23 -9.0° (c
D
1.0, MeOH); UV λmax (log ꢀ) 229 (4.19), 274 (3.90), 304 (sh, 3.68)
nm; IR νmax cm-1: 3400 (br s), 2950, 1665, 1590, 1520, 1420,
1280, 1035, 1020, 810, 770; CD (c 1.77 × 10-5 M) (∆ꢀ) 304
(+0.16), 298 (+0.23), 294 (+0.18), 286 (+0.47), 284 (+0.46),
278 (+0.52), 265 (+0.21), 253 (+0.34), 232 (-0.64), 212 (+0.75);
1H and 13C NMR, see Tables 2 and 3; FABMS (neg.) m/z (rel
int.) [M]- 566 (7), 552 (9), 377 (6), 321 (5), 301 (5), 287 (18),
285 (9), 229 (22), 219 (7), 210 (10), 197 (52), 195 (20), 179 (16),
171 (19), 155 (21), 153 (35), 139 (100), 105 (48), 89 (22).
Tetr a -O-m eth ylcu r ca p icyclosid e (2a ): amorphous pow-
der; mp 135-137 °C; UV λmax (log ꢀ) 230 (4.35), 276 (4.05),
308 (3.80) nm; [R]20 +58.3° [c 0.6, CHCl3-MeOH (1:1)]; IR
D
1-O-Meth ylisocu r cu ligin e Tetr a -O-m eth yl Eth er (8a ):
amorphous powder; Rf 0.33 [MeOH-CHCl3 (1:9)]; [R]23D +1.4°
(c 0.7, MeOH); IR νmax 3500 (br s), 2950, 1665 (CdO), 1590,
1520, 1410, 1280, 1120, 660 cm-1; UV λmax (log ꢀ) 229 (4.19),
274 (3.91), 307 (sh, 3.68) nm; CD (c 1.77 × 10-5 M) (∆ꢀ) 306
(-0.03), 294 (-0.29), 288 (-0.15), 277 (-0.20), 267 (-0.18),
262 (-0.21), 243 (0), 234 (+0.44), 225 (+0.28), 219 (0), [214
ν
max 3400 (br, OH), 2950, 1665 (CdO), 1590, 1520, 1420, 1280,
1020, 870, 800 cm-1; CD (c 1.87 × 10-5 M) (∆ꢀ) 311 (+1.30),
287 (0), 276 (-1.55), 250 (0), 235 (+2.93), 220 (+1.60), 212
(+2.43); H and 13C NMR, see Table 1; FABMS (pos.) m/z [M
1
+ H]+ 535 (4), 417 (5), 385 (8), 373 (12), 327 (12), 311 (12),
287 (10), 237 (27), 197 (40), 181 (42), 179 (33), 165 (49), 163
(25), 147 (43), 131 (26), 105 (32), 91 (100), 57 (51); HRFABMS
(pos.) m/z [M + H]+ 535.2208 (calcd for C27H35O11 535.2179).
P er a cetyla tion of 2a . Compound 2a (10 mg) was peracety-
lated with Ac2O-py at room temperature for overnight and
after general workup gave the peracetyl product 2b.
Tetr a -O-m eth ylcu r ca p icyclosid e Tr ia ceta te (2b): 1H
NMR data (CDCl3), see Table 1; HREIMS m/z [M]+ 660.2410
(calcd for C33H40O14 660.2418); EIMS m/z [M]+ 660 (4), 509
(3), 371 (24), 356 (6), 235 (8), 180 (16), 165 (100), 151 (10), 97
(10), 43 (12).
1
(+0.24), 208 (-0.42)]; H and 13C NMR, see Tables 2 and 3;
FABMS (neg.) m/z (rel int.) [M]- 566 (8), 551 (22), 377 (8), 287
(34), 269 (8), 229 (43), 197 (100), 179 (34), 139 (87), 87 (43).
Cu r ca p ita l (9): amorphous powder; Rf 0.28 [MeOH-H2O
(1:1), RP8]; IR νmax 3300 (br s), 1630, 1560, 1520, 1475, 1420,
1250, 1020, 870, 830, 790, 680 cm-1; UV λmax (log ꢀ) 221 (4.38),
1
250 (4.63), 276 (4.55), 309 (sh, 4.15), 376 (4.25) nm; H and
13C NMR, see Table 4; FABMS (neg.) m/z (rel int.) [M - H]-
309 (30), [M - 2H]- 308 (12), 279 (5), 203 (7), 171 (23), 137

Constituents of Curculigo
J ournal of Natural Products, 1999, Vol. 62, No. 5 739
(18), 113 (100), 89 (18), 87 (20), 77 (14), 75 (20), 64 (20);
HRFABMS (neg.) m/z [M - H]- 309.0412 (calcd for C17H9O6
309.0399).
by treating with CH2N2, was reacted with 2,2-dimethoxy-
propane (2.0 mL) and TsOH (2 mg) at 0 °C for 30 min, followed
by additional stirring for 30 min at room temperature. The
reaction mixture was then diluted with CHCl3, washed with
5% KHCO3 solution and H2O, dried (MgSO4), and evaporated
in vacuo to yield an essentially pure 12 (36 mg), a colorless
viscous liquid: [R]23D +84.3° (c 0.7, CHCl3); UV λmax (log ꢀ) 221
(sh, 4.55), 237 (sh, 4.33), 258 (4.46), 286 (3.97), 297 (3.80) nm;
CD (2.43 × 10-5 M) (∆ꢀ) 310 (0), 298 (0.11), 282 (0.26), 253
P r ep a r a tion of Tetr a m eth yl-(1R)-1-O-m eth yln ya sico-
sid e (10a ): (1R)-1-O-Methylnyasicoside (10) was O-methylated
by reacting with freshly prepared ethereal CH2N2 in the usual
manner, and the reaction mixture was separated on a Si gel
column chromatograph (230-400 mesh, 4% MeOH in CHCl3)
to give 10a : amorphous powder; [R]20 -1.0° (c 1.0, MeOH);
D
1
IR νmax 3400 (br, OH), 2940, 1510, 1460, 1420, 1260, 1240,
1140, 1080, 1020, 860, 820, 760 cm-1; UV λmax (log ꢀ) 258 (4.35),
285 (3.88), 298 (sh, 3.70) nm; CD (1.82 × 10-5 M) (∆ꢀ) 312 (0),
285 (+2.63), 250 (+7.42), 234 (+0.88), 212 (+14.43); 1H NMR
(CDCl3) δ 6.96 (1H, dd, J ) 1.7, 8.3 Hz, H-6′′), 6.90 (1H, d, J
) 1.4 Hz, H-2′), 6.89 (1H, dd, J ) 1.4, 8.1 Hz, H-6′), 6.88 (1H,
d, J ) 1.7 Hz, H-2′′), 6.81 (1H, d, J ) 8.1 Hz, H-5′), 6.74 (1H,
d, J ) 8.3 Hz, H-5′′), 4.55 (1H, d, J ) 7.6 Hz, Glc H-1), 4.40
(1H, d, J ) 6.1 Hz, H-1), 4.02 (1H, ddd, J ) 5.1, 5.3, 6.1 Hz,
H-2), 3.85 (3H, s, Ar-OMe), 3.83 (9H, s, Ar-OMe × 3), 3.80
(1H, m) and 3.70 (1H, m) (Glc H-6), 3.24 (3H, s, 1-OMe), 2.68
(1H, dd, J ) 5.1, 17.0 Hz) and 2.33 (1H, dd, J ) 5.3, 17.0 Hz)
(H-3); 13C NMR (CDCl3) δ 149.28 (s, C-4′′), 149.02 (s, C-4′),
148.97 (s, C-3′′), 148.60 (s, C-3′), 128.98 (s, C-1′), 124.73 (d,
C-6′′), 120.31 (d, C-6′), 114.40 (d, C-2′), 115.40 (s, C-1′′), 110.04
(d, C-5′′), 110.85 (d, C-2"), 110.81 (d, C-5′), 101.80 (d, Glc C-1),
84.37 (s, C-4), 84.37 (d, C-1), 82.78 (s, C-5), 78.83 (d, C-2), 76.16
(d, Glc C-5), 75.79 (d, Glc C-3), 72.93 (d, Glc C-2), 70.02 (d,
Glc C-4), 62.02 (t, Glc C-6), 56.97 (q, 1-OMe), 56.00 (q), 55.90
(q), 55.87 (q) and 55.85 (q) (4 × Ar-OMe), 22.63 (t, C-3);
FABMS (pos.) m/z [M + Na]+ 571 (100), [M]+ 548 (4), 437 (8),
459 (25), 371 (8), 329 (12), 289 (8), 176 (78), 154 (64), 136 (56),
77 (30).
(0.77), 240 (0), 234 (-0.25), 224 (0); H NMR (CDCl3) δ 6.97
(1H, dd, J ) 1.8, 8.2 Hz, H-6′), 6.96 (1H, d, J ) 1.8 Hz, H-2′),
6.90 (1H, dd, J ) 1.8, 8.2 Hz, H-6′′), 6.82 (1H, d, J ) 8.2 Hz,
H-5′), 6.80 (1H, d, J ) 1.8 Hz, H-2′′), 6.73 (1H, d, J ) 8.2 Hz,
H-5′′), 4.84 (1H, d, J ) 8.3 Hz, H-1), 3.96 (1H, dt, J ) 8.3, 4.9
Hz, H-2), 3.84 (9H, s, 3 × OMe), 3.82 (3H, s, 1 × OMe), 2.80
(1H, dd, J ) 17.2, 5.2 Hz, H-3a), 2.69 (1H, dd, J ) 17.2, 4.6
Hz, H-3b), 1.57 (3H, s, â-Me of acetonide), 1.54 (3H, s, â-Me of
acetonide); HREIMS m/z [M]+ 412.1886 (calcd for C24H28O6
412.1885); EIMS m/z [M]+ 412 (2), 397 (3), 354 (7), 337 (25),
295 (8), 189 (9), 175 (100), 165 (37), 151 (33), 131 (18), 107
(11), 43 (11).
Hyd r a tion of Tetr a -O-m eth yln ya sicosid e (1a ) a n d Its
1-O-Meth yl Der iva tive (10a ). The mixture of 1a 6 (36 mg),
HgO (15 mg), concentrated H2SO4 (0.13 mL), and H2O (3 mL)7
was heated at 60° for 30 min. The reaction mixture was diluted
with H2O (10 mL) and passed over an Amberlite XAD-2 column
(20 g) washed with H2O and MeOH in order. The MeOH
fraction (43 mg) was a mixture of 4a and 5a , which were
separated as mentioned above to give each about 9 mg.
Treatment of tetra-O-methyl-1-O-methylnyasicoside (10a ) (38
mg) under similar conditions and fractionation via an Amber-
lite XAD-2 column yielded a mixture (36 mg) of 4a , 5a , and
7a , which were separated on a Si gel column (10 g, 230-400
mesh) eluted with 4% MeOH in CHCl3 to give 7a (8 mg) and
a mixture (6 mg) of 4a and 5a .
P r ep a r a tion of Tetr a -O-m eth yltetr a h yd r on ya sicosid e
(11): A solution of tetramethylnyasicoside (1a ) (48 mg) in
MeOH (5 mL) was catalytically hydrogenated over 10% Pd/C
(2 mg)-1 atm H2 at room temperature for 1.5 h. After general
workup, a colorless viscous product (11, 46 mg) was obtained:
[R]20D -44.0° (c 1.0, MeOH); IR νmax 3400 (br, OH), 2950, 1510,
1460, 1420, 1260, 1230, 1140, 1070, 1020, 800, 760 cm-1; UV
λmax (log ꢀ) 229 (4.35), 279 (3.90) nm; CD (∆ꢀ) 299 (0), 281
Ack n ow led gm en t. This work was supported by NSC,
R.O.C., under grant NSC-86-2314-B-002-081.
1
Refer en ces a n d Notes
(0.03), 258 (0), 235 (-0.22), 218 (0); H NMR (CD3OD) δ 6.77
(1H, dd, J ) 1.4 Hz, H-2′), 6.68 (1H, d, J ) 1.4, 8.1 Hz, H-6′),
6.65 (1H, dd, J ) 1.4, 8.0 Hz, H-6′′), 6.62 (1H, d, J ) 8.1 Hz,
H-5′), 6.50 (1H, d, J ) 1.4 Hz, H-2′′), 6.47 (1H, d, J ) 8.0 Hz,
H-5′′), 4.36 (1H, d, J ) 7.4 Hz, H-1), 4.36 (1H, d, J ) 7.6 Hz,
Glc H-1), 3.87 (3H, s, OMe), 3.84 (m) and 3.70 (m) (Glc H-6),
3.80 (m, H-2), 3.73 (9H, s, OMe × 3), 3.40 (2H, m, Glc H-5,3),
3.35 (1H, m, Glc H-4), 3.30 (1H, m, Glc H-2), 2.30 (2H, m, H-5),
1.63 (1H, m) and 1.45 (1H, m) (H-3), 1.25 (2H, m, H-2);
HRFABMS (neg.) [M]- m/z 538.2382 (calcd for C27H38O11
538.2414); FABMS m/z [M]- 538 (28), [M - H]- 537 (100), 523
(10), 321 (10), 213 (24), 229 (10), 153 (37).
(1) Lee, S. S.; Chang, W. L.; Chen, C. H. Tetrahedron Lett. 1996, 37,
4405-4408.
(2) Chang, W. L.; Su, M. J .; Lee, S. S. J . Nat. Prod. 1997, 60, 76-80.
(3) Chifundera, K.; Palazzino, G.; Messana, I.; Liu, P.; Galeffi, C.;
Cannarsa, G. Phytochemistry 1994, 35, 1343-1348.
(4) Molecular modeling was performed by Systematic Search of Sybyl
using Tripos Force Fields (TRIPOS, Inc.) to obtain the favored
conformation of 2a with minimum energy.
(5) Chifundera, K.; Messana, I.; Galeffi, C.; De Vicente, Y. Tetrahedron
1991, 47, 4369-4374.
(6) Galeffi, C.; G. Multari, G.; Msonthi, J . D.; Nicoletti, M.; Marini-
Bettolo, G. B. Tetrahedron 1987, 43, 3519-3522.
(7) Stacy, G. W.; Mikulec, R. A. Org. Synth. 1955, Coll. Vol. 4, 13-15.
(8) Gaffield, W. Tetrahedron 1970, 26, 4093-4108.
P r ep a r a tion of Tetr a -O-m eth yln ya sicol 1,2-Aceton id e
(12): Tetra-O-methylnyasicol (34 mg),6 obtained from nyasicol2
NP980364T