Spectroscopic analyses and chemical transformation for structure elucidation of two novel indole alkaloids from Gelsemium elegans

Article abstract of DOI:10.1016/j.tetlet.2009.02.092

Two new monoterpenoid oxindole alkaloids, gelsevanillidine (1) having an additional vanillin residue on gelsenicine-type alkaloid and gelseoxazolidinine (2) possessing an unusual oxazolidine ring, were isolated from Gelsemium elegans. To confirm their str

Full text of DOI:10.1016/j.tetlet.2009.02.092

Tetrahedron Letters 50 (2009) 3341–3344
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Tetrahedron Letters
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Spectroscopic analyses and chemical transformation for structure elucidation
of two novel indole alkaloids from Gelsemium elegans
Yousuke Yamada a, Mariko Kitajima a, Noriyuki Kogure a, Sumphan Wongseripipatana b,
Hiromitsu Takayama a,
*
a Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
b Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10500, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
Two new monoterpenoid oxindole alkaloids, gelsevanillidine (1) having an additional vanillin residue on
gelsenicine-type alkaloid and gelseoxazolidinine (2) possessing an unusual oxazolidine ring, were iso-
lated from Gelsemium elegans. To confirm their structures, the chemical transformation of a humante-
nine-type alkaloid into gelsevanillidine (1) and the deacetoxy derivative of gelseoxazolidinine was
performed.
Received 10 January 2009
Revised 7 February 2009
Accepted 12 February 2009
Available online 20 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Gelsemium
Indole
Alkaloid
Gelsedine
Spectroscopy
Chemical transformation
Gelsemium elegans Benth. (Loganiaceae) is a toxic plant that is
widely distributed in Southeast Asia. Gelsemium plants are a rich
source of indole alkaloids: more than 70 alkaloids have been iso-
lated to this day, and they are classified into six types on the basis
of their chemical structures.1–3 G. elegans has been used in tradi-
tional Chinese medicine, and is the origin of ‘Yakatsu’, one of the
New alkaloid 1,10 named gelsevanillidine,11 was found to have
the molecular formula C27H28N2O5 from HRFABMS [m/z 461.2075
(MH+)]. UV spectroscopy (384, 314, 296 (sh), 247 (sh), 207 nm)
suggested the presence of a long conjugated system. 1H and 13C
NMR spectra (Table 1) showed readily assignable signals due to
the gelsenicine (5) part, including signals of four aromatic protons
[d 7.58 (d, H-9), d 7.30 (ddd, H-11), d 7.12 (ddd, H-10), d 6.96 (d, H-
12)], an Na-methoxy group [d 3.89 (3H, s)], and oxygenated protons
[d 4.38 (br dd, H-17), d 4.35 (dd, H-17), d 3.70 (overlapped, H-3)],
and confirmed the presence of a trisubstituted olefin group [dH
7.18 (br s, H-21), dC 130.9 (C-19), dC 139.6 (C-21)]. These spectral
data were very similar to those of gelsecrotonidine,9a the exception
being the existence of a 1,2,4-trisubstituted benzene ring system
[dH 7.10 (br d, H-23), dH 7.01 (br dd, H-27), dH 6.85 (d, H-26), dC
148.7 (C-24), dC 148.3 (C-25), dC 129.8 (C-22), dC 124.8 (C-27), dC
116.2 (C-26), dC 114.6 (C-23)] instead of a methyl carboxylate
group in gelsecrotonidine. Based on the allylic coupling of H-18
and H-21 as confirmed by 1H–1H COSY and the lack of H-19 pro-
tons, the olefin group was elucidated to be at C-19 position. Fur-
thermore, the trisubstituted olefin group and the trisubstituted
benzene ring system could be connected by HMBCs from the pro-
ton at d 7.18 (H-21) to the carbons at d 114.6 (C-23) and d 124.8 (C-
27) (Fig. 2). The substitution pattern of the benzene ring was pre-
sumed on the basis of NOE correlations (Fig. 2) from the proton at d
7.18 (H-21) to the two protons at d 7.10 (H-23) and d 7.01 (H-27),
and from the aromatic methoxy protons at d 3.90 to the proton at d
ancient medicines stored in the Shosoin repository in Japan.4
A
number of pharmacological activities, including analgesic,5 anti-
inflammatory,5 cytotoxic,6,7 and antitumor8 activities, of G. elegans
alkaloids have been reported.
In our continuing chemical studies on the Gelsemium alka-
loids,6,9 we were able to isolate two novel gelsedine-related alka-
loids, gelsevanillidine (1) and gelseoxazolidinine (2), from G.
elegans. Gelsevanillidine (1) possesses a side chain with a vanillin
residue, which is the first example of a monoterpenoid indole alka-
loid. Gelseoxazolidinine (2) consists of a hexacyclic skeleton with
an unprecedented oxazolidine ring. To confirm their unique struc-
tures, the chemical transformation of a known humantenine-type
Gelsemium alkaloid, rankinidine (4), into new alkaloid 1 and the
14-deacetoxy derivative of new alkaloid
2 was performed
(Fig. 1). In this Letter, we report the structure elucidation of these
two new alkaloids 1 and 2 by means of spectroscopic analyses and
chemical transformation.
* Corresponding author. Tel./fax: +81 43 290 2901.
E-mail address: htakayam@p.chiba-u.ac.jp (H. Takayama).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.092

3342
Y. Yamada et al. / Tetrahedron Letters 50 (2009) 3341–3344
R
OMe
O
O
14
H
N
H
3
OH
H
20
5
H
O
H
O
19
21
N
N
N
O
22
OMe
OMe
Gelsevanillidine (1)
R=OAc: Gelseoxazolidinine (2)
R=H: 14-Deacetoxy-
gelseoxazolidinine (3)
Figure 1. Structures of new alkaloids (1 and 2) and the 14-deacetoxy derivative of 2 (3).
Table 1
7.10 (H-23), as well as of the HMBCs depicted in Figure 2. Consid-
ering all these factors as well as the chemical shifts, we proposed
the presence of a p-hydroxy-m-methoxy-substituted benzene ring
system. The double bond between C-19 and C-21 was elucidated to
have the E-configuration based on the NOE correlation of the olefin
proton (H-21) to the proton at d 3.70 (overlapped, H-15). From
these data, the structure of gelsevanillidine was deduced to be that
shown as formula 1.
1H (600 MHz) and 13C (150 MHz) NMR data for gelsevanillidine (1) in CD3OD
Position
1
dH
dC
2
3
5
6
173.2
76.3
73.2
38.4
3.70 (overlapped)
4.56 (m)
2.59 (dd, 15.7, 4.8)
2.20 (dd, 15.7, 1.9)
To confirm the structure inferred from the spectroscopic analy-
sis above, we attempted to synthesize 1 from the known humant-
enine-type alkaloid rankinidine (4),12 which is one of the major
alkaloids in Gelsemium rankinii (Scheme 1). At the start of the syn-
thesis, rankinidine (4) was treated with 2,2,2-trichloroethyl chloro-
formate (TrocCl) in the presence of triethylamine in CH2Cl2 to give
carbamate 6 in 98% yield. Then, the double bond migration from C-
19–C-20 position to C-20–C-21 position was achieved in a quanti-
tative yield by using TMSCl and NaI13 in CH3CN to afford enamine-
carbamate 7. Enamine-carbamate 7 was then treated with m-CPBA
(3 equiv) in CH2Cl2 to afford keto-carbamate 8 in 31% yield, which
would be formed via oxidatively cleaved product Nb-formyl-carba-
mate 9,14 together with a mixture of aminal 10 and aldehyde 11 in
59% yield. The mixture of 10 and 11 could be converted into keto-
carbamate 8 by NaBH4 reduction (94% yield) followed by oxidative
cleavage of resulting diol 12 with NaIO4 in MeOH in 67% yield. Re-
moval of the Nb-carbamate in 8 with Zn and ammonium chloride in
MeOH gave a secondary amine that was spontaneously converted
into gelsenicine (5)13,15 in 69% yield. Condensation of gelsenicine
(5) and vanillin acetate (13) under acidic conditions with TiCl4 in
(CH2Cl)2 afforded 14 in 97% yield E-selectively to avoid the steric
hindrance between a bulky aromatic ring and the gelsenicine part.
Finally, removal of the acetyl group in 14 (K2CO3, MeOH) gave gels-
evanillidine (1) in 99% yield. Synthetic 1 was completely identical
in all respects with the natural one, thereby establishing its struc-
7
8
9
57.6
133.3
126.0
124.7
129.4
107.8
139.1
29.6
7.58 (d, 7.7)
10
11
12
13
14
15
16
17
7.12 (ddd, 7.7, 7.7, 1.1)
7.30 (ddd, 7.7, 7.7, 1.1)
6.96 (d, 7.7)
2.39 (2H, overlapped)
3.70 (overlapped)
2.72 (m)
4.38 (br dd, 11.3, 1.4)
4.35 (dd, 11.3, 3.0)
2.32 (3H, br s)
40.5
40.6
62.6
18
19
20
21
22
23
24
25
26
27
Na–OMe
24-OMe
15.1
130.9
184.2
139.6
129.8
114.6
148.7
148.3
116.2
124.8
63.9
7.18 (br s)
7.10 (br d,1.5)
6.85 (d, 8.2)
7.01 (br dd, 8.2, 1.5)
3.89 (3H, s)
3.90 (3H, s)
56.4
ture including its absolute configuration {natural: ½a D22
ꢁ 79:9
ꢀ
(c 0.24, MeOH), synthetic: ½a D22
ꢁ 81:8 (c 0.12, MeOH)}.
ꢀ
17
14
H
OMe
24
New alkaloid 2,10 named gelseoxazolidinine,16 was shown to
have the molecular formula C23H28N2O6 from HREIMS [m/z
428.1937 (M+)]. UV and NMR spectra indicated the presence of
the characteristic Na-methoxyoxindole chromophore. 1H and 13C
NMR data (Table 2) revealed the presence of a nonsubstituted A
ring of the oxindole system, an Na-methoxy group (dH 4.04, dC
63.5), an oxymethine group (dH 3.61, dC 76.7, C-3), a methine group
bearing nitrogen (dH 3.46, dC 69.8, C-5), two oxymethylene groups
(dH 4.32, 4.26, dC 62.9, C-17 and dH 3.62, 3.41 dC 75.4, C-21), and an
oxymethine group (dH 6.08, dC 67.7, C-14) to which an acetoxy
group [dH 2.00 (3H, s), dC 170.2, 21.1] is attached. 1H–1H COSY cor-
relation between the H-3 oxymethine proton at d 3.61 and the low-
field methine proton at d 6.08 indicated that an acetoxy group was
attached to C-14. This inference was confirmed on the basis of the
HMBC between the proton at d 6.08 (H-14) and the acetoxy car-
bonyl carbon at d 170.2 (Fig. 3). The configuration of the acetoxy
group at C-14 was shown to be b from the coupling constant of
16
H
23
27
O
H
3
9
H
H
22
10
11
OH
6
5
25
26
8
7
15
21
20 19
H
2
N
Me H
H
13
O
12
N
18
HMBC
OMe
Me
H
O
24
23
O
H
H
H
OH
25
26
15
21
27
H
20 19
N
H
Me
18
O
N
NOE
OMe
Figure 2. Selected HMBC and NOE correlation of gelsevanillidine (1).

Y. Yamada et al. / Tetrahedron Letters 50 (2009) 3341–3344
3343
O
O
O
O
H
TMSCl, NaI
CH3CN
m-CPBA, CH2Cl2
-40 °C, 2 h
H
H
H
OH
OH
OH
20
20
19
H
O
H
O
Troc
H
O
Troc
H
N
N
N
NH
+
CHO
N
N
N
rt, 2 h
quant
10 and 11: 59%
8: 31%
21
R
Troc
OMe
OMe
OMe
TrocCl, NEt3
CH2Cl2, rt, 2 h
98%
R=H: Rankinidine (4)
R=Troc: 6
7
10
11
O
H
O
H
N
Tr oc
CHO
9
O
H
O
H
OH
O
NaBH4, MeOH
rt, 1 h, 94%
NaIO4, MeOH
rt, 3 h, 67%
Zn, NH4Cl, MeOH
H
O
Troc
H
O
NH
NH
N
N
Troc
rt, 4 h, 69%
OH
OMe
OMe
(SM recovered 20%)
(SM recovered 24%)
12
8
OMe
OAc
OMe
OR
O
H
O
H
OHC
13
H
N
H
O
19
N
O
N
N
TiCl4, (CH2Cl)2
reflux, 24 h, 97%
OMe
OMe
Gelsenicine (5)
R=Ac: 14
R=H: Gelsevanillidine (1)
K2CO3, MeOH
rt, 11 h, 99%
Scheme 1.
Table 2
1H (400 MHz) and 13C (125 MHz) NMR data for gelseoxazolidinine (2) in CDCl3
O
O
O
Me
H
O
Me
H
Position
2
O
O
14
dH
dC
14
H
N
H
15
20
19
2
3
5
6
171.5
76.7
69.8
37.4
H
H
19
21
20
3.61 (d, 1.8)
3.46 (m)
2.19 (dd, 15.7, 2.8)
2.14 (dd, 15.7, 4.2)
H
5
H
H
21
N
N
H
O
O
22O
N
O
22
H
H
OMe
OMe
7
8
9
53.6
131.2
125.0
123.1
128.3
106.8
138.5
67.7
7.34 (d, 7.5)
HMBC
NOE
10
11
12
13
14
15
16
17
7.08 (ddd, 7.5, 7.5, 1.1)
7.28 (ddd, 7.5, 7.5, 1.1)
6.93 (d, 7.5)
Figure 3. Selected HMBC and NOE correlation of gelseoxazolidinine (2).
6.08 (br s)
2.44 (br d, 6.4)
2.66 (m)
4.32 (dd, 10.8, 4.2)
4.26 (br d, 10.8)
0.85 (3H, dd, 7.2, 7.2)
2.80 (dq, 14.1, 7.2)
1.66 (dq, 14.1, 7.2)
signals (d 89.3) were observed in the 1H and 13C NMR spectra,
respectively, suggesting the existence of an hemiaminal methylene
group (C-22). HMBCs between the hemiaminal protons and the
oxymethylene carbon at d 75.4 (C-21) and carbons bearing nitro-
gen (C-5 and C-20) implied the existence of an oxazolidine ring
consisting of N-4, C-20, C-21, O, and C-22 positions. The NOE cor-
relation of H-14 to H-19 revealed the b-ethyl configuration at C-
20. Therefore, the structure of gelseoxazolidinine was deduced to
be that shown as formula 2.
As this kind of hexacyclic framework that includes an oxazoli-
dine ring is the first instance of a natural product, we attempted
to prepare the skeleton and to compare spectroscopic data. From
a biogenetic point of view, gelseoxazolidinine (2) would be formed
from 14-acetoxygelselegine (17)6 by adding a C1 unit between Nb
and C-21 primary alcohol. With compound 12 as the synthetic
intermediate for gelsevanillidine (Scheme 1) in hand, we utilized
it to construct the basic skeleton of gelseoxazolidinine, that is,
the 14-deacetoxy derivative of gelseoxazolidinine. According to
our previous study,13 diol 12 was converted into epoxide 15 via
45.8
35.7
62.9
18
19
8.9
26.6
a
20
21
3.62 (d, 8.3)
3.41 (d, 8.3)
4.56 (d, 7.2)
4.35 (d, 7.2)
4.04 (3H, s)
75.4
22
89.3
Na–OMe
14-OCOMe
14-OCOMe
63.5
170.2
21.1
2.00 (3H, s)
a
Under CDCl3 signal.
the proton at C-14 (J3,14 = 1.8 Hz), as in the case of other com-
pounds having a hydroxyl or an acetoxy group at C-14.7,9a,e,h Fur-
thermore, low-field methylene proton (d 4.56, 4.35) and carbon

3344
Y. Yamada et al. / Tetrahedron Letters 50 (2009) 3341–3344
Takayama, H. Chem. Pharm. Bull. 2008, 56, 870–872; (d) Kogure, N.; Someya, A.;
O
H
Urano, A.; Kitajima, M.; Takayama, H. J. Nat. Med. 2007, 61, 208–212; (e)
Kogure, N.; Ishii, N.; Kitajima, M.; Wongseripipatana, S.; Takayama, H. Org. Lett.
2006, 8, 3085–3088; (f) Kogure, N.; Nishiya, C.; Kitajima, M.; Takayama, H.
Tetrahedron Lett. 2005, 46, 5857–5861; (g) Kitajima, M.; Kogure, N.; Yamaguchi,
K.; Takayama, H.; Aimi, N. Org. Lett. 2003, 5, 2075–2078; (h) Kitajima, M.;
Urano, A.; Kogure, N.; Takayama, H.; Aimi, N. Chem. Pharm. Bull. 2003, 51,
1211–1214.
(i) Zn, AcOH
rt, 4 h
TMAD, n-Bu3P
H
O
Tr oc
NH
O
12
N
DMF
rt, 4 h, 81%
(ii) standing at
rt for 5 days
50%
OMe
15
10. The roots of Gelsemium elegans Benth. were collected in Phu Laung, Loei
Province, Thailand, and were identified by Dr. Sumphan Wongseripipatana. A
voucher specimen was deposited at the Faculty of Pharmaceutical Sciences,
Chulalongkorn University, Thailand. The roots of G. elegans (1353 g, dry weight)
were extracted with MeOH to give a MeOH extract (109.7 g). The MeOH extract
was dissolved in 20% MeOH/H2O and was extracted successively with n-
hexane, AcOEt, 5% MeOH/CHCl3, and n-BuOH. The 5% MeOH/CHCl3 extract
(6.33 g) was separated by SiO2 flash column chromatography with a CHCl3/
MeOH gradient to give seven fractions. The fraction eluted with 10% MeOH/
CHCl3 (164.5 mg) was purified by MPLC (3% MeOH/AcOEt and then 7% MeOH/
CHCl3) to give gelsevanillidine (1, 5.6 mg). Gelseoxazolidinine (2, 1.7 mg) was
obtained from the crude base (6.76 g) that was prepared from the roots of G.
elegans (600 g, dry weight) by a conventional method. The crude base was
separated by amino silica gel open column chromatography with a CHCl3/
MeOH gradient, and then with an n-hexane/CHCl3/MeOH gradient. The fraction
that was eluted with 70–100% CHCl3/n-hexane (552.5 mg) was purified by SiO2
flash column chromatography (CHCl3/MeOH gradient) and then by MPLC (5%
MeOH/AcOEt) to give gelseoxazolidinine.
R
O
O
H
14
H
Formalin
p-TsOH
20
20
H
O
H
O
21
21
N
N
H
N
O
N
Benzene
45 °C, 2.5 h
86%
OH
22
OMe
OMe
R=H: Gelselegine (16)
R=OAc: 14-Acetoxygelselegine (17)
14-Deacetoxy-
gelseoxazolidinine (3)
Scheme 2.
11. Gelsevanillidine (1): ½a D22
ꢀ
ꢁ 79:9 (c 0.24, MeOH); 1H and 13C NMR data, see Table
the modified Mitsunobu reaction [N,N,N0,N0-tetramethylazodicarb-
oxamide (TMAD), n-Bu3P, DMF] in 81% yield (Scheme 2). Removal
of the Nb-Troc group (Zn, AcOH) afforded a primary amine, which
was gradually cyclized at C-20 position to generate gelselegine
(16).17 Compound 16 was then treated with formalin in the pres-
ence of a catalytic amount of p-TsOH in benzene at 45 °C for
2.5 h to afford target molecule 318 in 86% yield. The 1H and 13C
NMR data and the CD spectral data of 3 resembled those of gels-
eoxazolidinine (2) well, except for the signals around C-14 position
bearing a b-acetoxy group. Thus, we propose that the structure of
gelseoxazolidinine is as shown in formula 2.
In conclusion, the novel structures of two gelsedine-related
oxindole alkaloids, gelsevanillidine (1) and gelseoxazolidinine (2),
isolated from G. elegans were elucidated by spectroscopic and
chemical methods. Gelsevanillidine is the first example of a mono-
terpenoid indole alkaloid with an additional vanillin residue, and
gelseoxazolidinine is a novel skeletal type alkaloid consisting of a
hexacyclic structure with an oxazolidine ring.
1; UV (MeOH) kmax nm (loge) 384 (3.57), 314 (4.05), 296 (sh, 4.01), 247 (sh,
4.02), 207 (4.46); IR (ATR)
m/z 461 (MH+); HRFABMS m/z 461.2075 (MH+, calcd for C27H29N2O5,
461.2076); CD (c 0.219 mmol/L, MeOH, 24 °C) (k nm) 0 (352), +2.81 (306),
m
max cmꢁ1 3263 (br), 2919, 1719, 1578, 1034; FABMS
D
e
0 (278), ꢁ8.15 (258), 0 (243), +3.64 (236), 0 (227), ꢁ23.34 (211).
12. Rankinidine used in this study was isolated from G. rankinii: Schun, Y.; Cordell,
G. A. J. Nat. Prod. 1986, 49, 806–808.
13. Takayama, H.; Tominaga, Y.; Kitajima, M.; Aimi, N.; Sakai, S. J. Org. Chem. 1994,
54, 4381–4385.
14. The possible mechanism for the oxidative cleavage of the enamine double
bond with excess m-CPBA is shown below.
O
H
O
H
O
Ar
HO
O
H
H
N
N
OH
O
Troc
Troc
7
Ar
HO
O
O
H
O
H
O
H
N
Acknowledgments
O
H
N
H
Troc
CHO
Troc
This work was supported by a Grant-in-Aid for Scientific Re-
search from the Japan Society for the Promotion of Science, the Re-
search Foundation for Pharmaceutical Sciences, and The Uehara
Memorial Foundation.
O
O
O
9
Ar
15. Du, X.; Dai, Y.; Zhang, C.; Lu, S.; Liu, Z. Acta Chim. Sin. 1982, 40, 1137–1141.
16. Gelseoxazolidinine (2): ½a D23
ꢀ
ꢁ 93:8 (c 0.07, MeOH); 1H and 13C NMR data, see
Table 2; UV (MeOH) kmax nm (loge) 284 (sh, 3.24), 256 (3.65), 209 (4.25); EIMS
References and notes
m/z (%) 428 (M+, 17), 398 (78), 367 (77), 121 (100); HREIMS m/z 428.1937 (M+,
calcd for C23H28N2O6, 428.1947); CD (c 0.369 mmol/L, MeOH, 24 °C)
0 (305), ꢁ4.46 (260), 0 (249), +7.81(236), 0 (222), ꢁ9.30 (212).
De (k nm)
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9. (a) Yamada, Y.; Kitajima, M.; Kogure, N.; Takayama, H. Tetrahedron 2008, 64,
7690–7694; (b) Kogure, N.; Kobayashi, H.; Ishii, N.; Kitajima, M.;
Wongseripipatana, S.; Takayama, H. Tetrahedron Lett. 2008, 49, 3638–3642;
(c) Kogure, N.; Ishii, N.; Kobayashi, H.; Kitajima, M.; Wongseripipatana, S.;
17. Lin, L.; Cordell, G. A.; Ni, C.; Clardy, J. Phytochemistry 1990, 29, 3013–3017.
18. 14-Deacetoxygelseoxazolidinine (3): 1H NMR (400 MHz, CDCl3) d 7.40 (1H, d,
J = 7.4 Hz, H-9), 7.27 (1H, ddd, J = 7.4, 7.4, 1.2 Hz, H-11), 7.09 (1H, ddd, J = 7.4,
7.4, 1.2 Hz, H-10), 6.92 (1H, d, J = 7.4 Hz, H-12), 4.57 (1H, d, J = 7.3 Hz, H-22),
4.38 (1H, d, J = 7.3 Hz, H-22), 4.21 (1H, dd, J = 12.0, 2.8 Hz, H-17), 4.20 (1H, br d,
J = 12.0 Hz, H-17), 4.01 (3H, s, Na–OMe), 3.59 (1H, d, J = 7.8 Hz, H-21), 3.57 (1H,
d, J = 6.4 Hz, H-3), 3.48 (br ddd, J = 9.2, 4.2, 3.1 Hz, H-5), 3.37 (1H, d, J = 7.8 Hz,
H-21), 2.75 (2H, overlapped, H-14, H-19), 2.62 (1H, br dddd, J = 9.2, 6.0, 2.8,
2.8 Hz, H-16), 2.38 (1H, br ddd, J = 11.2, 6.0, 2.5 Hz, H-15), 2.14 (1H, dd, J = 15.8,
3.1 Hz, H-6), 2.11 (1H, dd, J = 15.8, 4.2 Hz, H-6), 2.04 (1H, ddd, J = 15.5, 11.2,
6.4 Hz, H-14), 1.60 (1H, dq, J = 14.4, 7.5 Hz, H-19), 0.87 (3H, dd, J = 7.5, 7.5 Hz,
H3-18); 13C NMR (125 MHz, CDCl3) d 172.4 (C-2), 138.1 (C-13), 132.3 (C-8),
127.9 (C-11), 125.4 (C-9), 123.2 (C-10), 106.6 (C-12), 89.4 (C-22), 77.7 (C-20),
75.7 (C-21), 74.2 (C-3), 70.9 (C-5), 63.3 (Na–OMe, C-17), 55.9 (C-7), 38.4 (C-15),
37.6 (C-16), 37.5 (C-6), 26.7 (C-19), 23.0 (C-14), 9.2 (C-18); UV (MeOH) kmax nm
(log
HREIMS m/z 370.1892 (M+, calcd for C21H26N2O4, 370.1892); CD (c 0.351 mmol/
L, MeOH, 24 °C) (k nm) 0 (300), ꢁ1.46 (278), ꢁ5.73 (262), 0 (250), +11.08
(234), 0 (223), ꢁ19.82 (212).
e
) 257 (3.66), 208 (4.24); EIMS m/z (%) 370 (M+, 33), 340 (95), 309 (100);
D
e