Novel acylated lipo-oligosaccharides from the tubers of Ipomoea batatas

Article abstract of DOI:10.1016/j.carres.2008.12.022

Nine new lipo-oligosaccharides, batatosides H-P, were isolated from the tubers of Ipomoea batatas (Convolvulaceae). Spectral and chemical methods allowed to characterize them as tetra- or penta-saccharides that form a macrolactone with the aglycone, (11S)

Full text of DOI:10.1016/j.carres.2008.12.022

Carbohydrate Research 344 (2009) 466–473
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Novel acylated lipo-oligosaccharides from the tubers of Ipomoea batatas
*
Yong-Qin Yin, Jun-Song Wang, Jian-Guang Luo, Ling-Yi Kong
Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
Nine new lipo-oligosaccharides, batatosides H–P, were isolated from the tubers of Ipomoea batatas (Con-
volvulaceae). Spectral and chemical methods allowed to characterize them as tetra- or penta-saccharides
that form a macrolactone with the aglycone, (11S)-hydroxyhexadecanoic acid (jalapinolic acid), the abso-
lute configuration of which was established by Mosher’s method. Batatosides L and O showed a weak
inhibitory effect on the growth of Hep-2 cells, while the others proved to be inactive.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 29 September 2008
Received in revised form 23 December 2008
Accepted 24 December 2008
Available online 3 January 2009
Keywords:
Pentasaccharide
Lipo-oligosaccharides
Cytotoxic activity
Ipomoea batatas
Convolvulaceae
1. Introduction
chloroform-soluble material was subjected to successive column
chromatography over silica gel, Sephadex LH-20, MPLC, and HPLC
A group of glycosides of hydroxyaliphatic acids, such as jalapinol-
ic acid, convolvulonic acid, and ipurolic acid, have already been char-
to yield compounds 1–9. The alkaline hydrolysis of each compound
produced an organic acid fraction and a water-soluble aliphatic
hydroxyacid glycoside. Peaks in the chromatograms of the organic
acid fraction were identified by comparison with authentic sam-
ples16,17 as isobutyric acid methyl ester (tR 2.368 min, m/z 101 (32)
[MꢀH]ꢀ, 87 (48), 71 (50), 43 (100), in 7–9); (S)-2-methylbutyric acid
methyl ester (tR 3.593 min, m/z 117 (5) [M+H]+, 101 (23), 88 (87), 57
(100), 41 (57), in 1, 2, and 4–7); n-decanoyl acid methyl ester (tR
11.422 min, m/z 116 (10) [M]+Å, 143 (45), 87 (64), 74 (100), 55
(55), 43 (80), in 3 and 9); trans-cinnamic acid methyl ester (tR
12.498 min, m/z 131 (100) [M]+Å, 103 (76), 77 (35), in 1–9); and n-
dodecanoyl methyl ester (tR 14.020 min, m/z 162 (45) [M]+Å, 215
(23), 171 (31), 143 (55), 87 (85), 74 (100), 55 (86), 43 (96), 41
(56), in 1–6 and 8). The ether extract (1.1 mg) from the alkaline
hydrolysis of 1 was purified by RP-C18 chromatography, eluted with
1:3 MeOH–H2O, to give 2-methylbutyric acid (0.3 mg). This was
proved to be in the S-configuration by comparing the optical rotation
acterized in the tubers of the genus Ipomoea (Convolvulaceae).1–5
D-
Glucose, D-fucose, L-rhamnose, and L-quinovose are the main mono-
saccharide constituents and are occasionally esterified with short
chain fatty acids. The hydroxyacid aglycone usually cyclizes in the
form of a macrocyclic lactone involving one hydroxyl of the oligosac-
charide chain. Such type of fatty acyl glycoside has been character-
ized previously in various plant extracts, and was named as ‘resin
glycoside’.6–10 Some ‘resin glycosides’ have been claimed to show
antifungal,11 antibacterial,12 and cytotoxic13 activities, as well as
phytogrowth inhibition properties.14 Ipomoea batatas L. is an impor-
tant food produced throughout the world which is known under the
common name of sweet potato, and is used independently in tradi-
tional medicinein China to eliminate abnormalsecretions (apoceno-
sis) and to promote hemostasis.15 We reported previously on the
isolation of several ‘resin glycosides’, batatosides A–G and simonin
IV16 and batatosides I–II17 from I. batatas. From theHPLC–ESIMS pro-
files of extracts from this species, several other glycosides were fur-
ther detected. We now report on the isolation of nine new ether-
soluble ‘resin glycosides’ 1–9, their structure elucidation, and some
studies of their cytotoxic activity.
25
(½aꢁD +19.0) with that of authentic (S)-2-methylbutyric acid. The
structures of the glycosidic acids (Chart 1) were determined by com-
parison of their spectral data with those reported as operculinic acid
A (10)18 for 1 and 2, operculinic acid E (11)19 for 3–5, simonic acid A
(12)18 for 6 and 7, and simonic acid B (13)20 for 8 and 9. Subsequent
acidic hydrolysis of glycosidic acids liberated the aglycone, 11-
hydroxyhexadecanoic acid, which was converted to 11-hydroxy-
hexadecanoic acid methyl ester (14) and then to its methoxyphenyl-
acetic acid (MPA) derivative (15 and 16) (Scheme 1). The chemical
2. Results and discussion
A 95% ethanol extract of the dried tubers of I. batatas was sus-
pended in water and partitioned with chloroform. The jalapin-like
RS
H10
RS
H12
shift differences of 15 and 16 Dd
¼ 0:06, Dd
¼ 0:13,
* Corresponding author. Tel.: +86 25 85391289; fax: +86 25 85301528.
E-mail address: lykong@jlonline.com (L.-Y. Kong).
Cna = trans-cinnamoyl; Deca = n-decanoyl; Dodeca = n-dodecanoyl; Iba = 2-meth-
ylbutanoyl; Mba = (2S)-methylbutanoyl.
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.12.022

Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
Fuc
HO
467
OH
Glc
HO
O
O
O
O
HO
O
11S
HO
Rha
11S
Rha
O
O
O
O
Rha'
O
Rha'
O
HO
O
O
O
HO
Rha''
O
O
O
Rha''
O
O
R5O
R1O
R5O
R4O
OR1
O
R4O
R3O
OR2
R3O
OR2
1
2
3
4
5
1
2
3
4
5
R
R
R
R
R
R
R
H
R
R
R
3
4
5
6
7
Dodeca
H
Cna
Cna
Cna
Cna
H
H
Deca
H
1
2
8
9
Mba
Mba
Iba
Cna
H
H
Dodeca
Dodeca
Dodeca
Iba
Glc
Glc
Rha
Rha
H
Dodeca
Dodeca
Mba
Mba
H
Cna
Cna
Cna
Mba
H
Dodeca
Mba
H
Rha
Rha
Cna
Iba
H
Deca
Fuc
HO
OH
O
O
Glc
HO
HO
O
O
O
11S
Rha
O
HO
11S
O
Rha
O
Rha'
O
HO
O
HO
Rha'
O
O
HO
Rha''
O
OH
Rha''
RO
O
OH
O
HO
HO
O
RO
HO
OH
O
HO
HO
O
OH
HO
OH
11
12
R=H
R=Rha
10 R=Glc
13
R=Rha
Chart 1. Structures of compounds 1–9 and the corresponding glycosidic acids 10–13.
O
OH
CH2N2
H2SO4
MeO
KOH
1–9
10–13
MeO
14
O
OR
(-0.07)
DCC, DMAP
(R) or (S)-MPA
(+0.06)
(-0.03)
15
R = (R)-MPA
R = (S)-MPA
16
Scheme 1. Conversion of 1–9 to the aglycone methyl ester 14 and its MPA derivatives (15 and 16).
Dd(R–S) values are given in ppm.
RS
Dd
¼ 0:07 ppm)29–33 made it possible to conclude that the chiral
two trans-coupled olefinic protons at dH 6.63 (d, J 16.0 Hz, H-2 of
Cna) and 7.88 (d, J 16.0 Hz, H-3 of Cna), a multiplet due to five pro-
tons at dH 7.27–7.45 (m, C6H5 of Cna), and at dH 0.79 (t, J 7.4 Hz, H-4
of Mba), 1.02 (d, J 7.0 Hz, CH3-2 of Mba), and 2.38 (m, H-2 of Mba).
Also a methyl triplet signal at 0.88 ppm and a triplet-like signal for
a methylene group at C-2 (2.48 ppm) of a dodecanoyl group, and
two signals at 2.27 (1H, m) and 2.44 (1H, m) ppm of the non-equiv-
alent protons of the methylene group at C-2 in the aglycone moiety
were observed, suggesting a macrocyclic lactone-type structure. A
group of four non-anomeric ring proton signals was found to be
paramagnetically shifted to d 5.92, 6.33, 6.00, and 6.10 (Table 1),
reflecting the presence of four sites of acylation. The HMQC spec-
trum of 1 indicated that anomeric carbons signals at 104.3, 98.5,
100.3, 103.3, and 105.5 ppm (Table 2) were correlated with the
anomeric protons at 4.69 (d, J 7.5 Hz), 5.50 (br s), 5.77 (br s),
H16
C-11 of the aglycone is in the S-configuration. GC–MS of the aqueous
layers from all acidic hydrolyses allowed to determine the sugar
constituents.
Batatoside H (1) and I (2), obtained as amorphous white pow-
ders, gave quasi-molecular ion at m/z 1419.7647 [M+Na]+ and
1419.7675 [M+Na]+, respectively, in the positive-ion HRESIMS,
which suggested the same molecular formula C72H116O26. Alkaline
hydrolysis afforded operculinic acid A (10),18 and dodecanoic, 2-
methylbutyric, and trans-cinnamic acids. These organic acids were
determined by GC–MS analysis. 2-Methylbutyric acid was found to
have the S-configuration by comparison of its optical rotation value
with that of an authentic sample. All these evidences suggested
that 1 and 2 were isomeric. The 1H NMR data of 1 (Table 1) exhib-
ited four doublet methyl signals for the four 6-deoxyhexose units,

468
Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
Table 1
1H NMR [dY (J, Hz)] data of compounds 1–5 (C5D5N, 600 MHz)
Position
1
2
3
4
5
Fuc-1
4.69 (d, 7.5)
4.71 (d, 7.5)
2
3
4
5
6
4.16 (dd, 7.5, 9.4)
4.13 (dd, 9.4, 3.0)
3.95 (d, 3.0)
3.73 (br q, 7.0)
1.49 (d, 6.4)
4.14 (dd, 7.5, 9.8)
4.03 (dd, 9.8, 3.5)
3.95 (d, 3.5)
3.75 (br q, 6.4)
1.50 (d, 6.4)
RhaI-1
5.50 (br s)
5.50 (br s)
5.60 (br s)
5.60 (br s)
5.60 (br s)
2
3
4
5
6
5.92 (br s)
5.00 (dd, 3.1, 9.4)
4.24 (t, 9.4)
4.31 (dq, 9.4, 6.2)
1.64 (d, 6.2)
5.93 (br s)
5.00 (dd, 3.3, 9.3)
4.16 (t, 9.5)
4.48 (dq, 9.5, 6.2)
1.63 (d, 6.2)
6.06 (br s)
5.08 (dd, 3.1, 9.6)
4.24 (t, 9.6)
4.43 (dq, 9.6, 7.0)
1.63 (d, 7.0)
6.04 (br s)
5.08 (dd, 3.1, 9.5)
4.25 (t, 9.5)
4.41 (dq, 9.5, 6.2)
1.66 (d, 6.2)
6.06 (br s)
5.08 (dd, 3.1, 9.3)
4.24 (t, 9.3)
4.42 (dq, 9.3, 6.2)
1.63 (d, 6.2)
RhaII-1
5.77 (br s)
6.33 (br s)
4.75 (dd, 3.4, 9.2)
4.32 (t, 9.2)
4.36 (dq, 9.2, 6.1)
1.66 (d, 6.1)
5.86 (d, 1.6)
6.30 (br s)
4.50a
6.10 (br s)
6.06 (br s)
4.72 (dd, 3.1, 9.5)
4.32 (t, 9.5)
4.41 (dq, 9.5, 6.1)
1.69 (d, 6.1)
6.18 (br s)
4.95 (br s)
5.77 (dd, 3.1, 9.5)
4.60 (t, 9.5)
4.41 (dq, 9.5, 6.1)
1.64 (d, 6.1)
6.06 (br s)
6.01 (br s)
4.73 (dd, 3.1, 9.5)
4.27 (t, 9.5)
4.38 (dq, 9.5, 6.0)
1.70 (d, 6.0)
2
3
4
5
6
4.79 (dd, 3.4,9.8)
4.00a
1.56 (d, 6.2)
RhaIII-1
6.27 (br s)
6.35 (br s)
6.19 (br s)
5.71 (br s)
6.20 (br s)
2
3
4
5
6
5.25 (br s)
6.31 (br s)
4.82 (dd, 3.5, 9.9)
5.84 (t, 9.8)
4.48 (dq, 9.5, 6.2)
1.68 (d, 5.7)
6.24 (br s)
5.95 (br s)
4.72 (dd, 3.3, 9.8)
5.81 (t, 9.8)
4.41 (dq, 9.8, 6.2)
1.49 (d, 6.2)
6.23 (br s)
4.80 (dd, 3.2, 9.8)
5.84 (t, 9.8)
4.50 (dq, 9.8, 6.2)
1.56 (d, 6.2)
6.00 (dd 3.1, 10.0)
6.10 (t, 10.0)
4.52 (dq, 10.0, 6.2)
1.47 (d, 6.2)
4.79 (dd, 2.5, 10.0)
5.84 (t, 10.0)
4.50 (dq, 10.0, 6.2)
1.56 (d, 6.2)
Glc-1
5.05 (d, 7.7)
3.92 (dd, 7.7, 9.0)
4.17 (t, 9.0)
5.06 (d, 7.7)
3.93 (dd, 7.7, 8.9)
4.09 (t, 8.9)
4.87 (d, 7.6)
3.88 (m)
4.14 (m)
4.12 (m)
3.84 (m)
4.31 (dd, 5.1, 11.5)
4.44 (dd, 2.2, 11.5)
2.27 (m)
4.93 (d, 7.6)
3.87a
4.17 (t, 8.9)
4.11 (t, 8.9)
3.85a
4.32 (dd, 5.1, 11.5)
4.42 (dd, 2.2, 11.5)
2.25 (m)
4.87 (d, 7.6)
3.88a
4.14 (t, 8.9)
4.12 (t, 8.9)
3.84a
4.31(dd, 5.1, 11.5)
4.44 (dd, 2.2, 11.5)
2.25 (m)
2
3
4
5
6
3.80 (t, 9.0)
3.88 (t, 8.9)
3.79 (ddd, 2.6, 5.8, 9.0)
4.07 (dd, 5.8, 11.7)
4.38 (dd, 2.6, 11.7)
2.27 (m)
3.79 (ddd, 2.2, 5.9, 8.9)
4.39 (dd, 2.2, 12.0)
4.05 (dd, 5.9, 12.0)
2.28 (m)
Jal-2
2.44 (m)
2.43 (m)
2.42 (m)
2.37 (m)
2.39 (m)
11
16
3.85 (m)
0.79 (t, 7.4)
3.85 (m)
0.87 (t, 7.1)
3.88 (m)
0.83 (t, 7.2)
3.88 (m)
0.83
3.88 (m)
0.85 (t, 7.0)
Cna-2
3
6.63 (d, 16.0)
7.88 (d, 16.0)
6.63 (d, 16.0)
7.88 (d, 16.0)
6.46 (d, 15.9)
7.74 (d, 15.9)
6.60 (d, 15.9)
7.88 (d, 15.9)
6.46 (d, 15.9)
7.74 (d, 15.9)
Deca-2
10
2.50 (m)
0.83 (t, 6.9)
Dodeca-2
12
2.48 (t, 7.3)
0.88 (t, 6.9)
2.48 (t, 7.3)
0.88 (t, 6.9)
2.33 (t, 7.0)
0.87 (t, 7.2)
2.48 (m)
0.87 (t, 7.1)
2.46 (m)
0.87 (t, 6.9)
Mba-2
2-CH3
4
2.38 (m)
1.02 (d, 7.0)
0.79 (t, 7.4)
2.38 (m)
1.02 (d, 7.0)
0.79 (t, 7.4)
2.78 (m)
1.01 (d, 7.0)
1.21a
2.46 (m)
0.82 (d, 7.4)
1.08 (d, 7.0)
a
Signal pattern unclear due to overlapping.
6.27 (br s), and 5.05 (d, J 7.7 Hz) ppm, respectively. All protons
were assigned sequentially within each saccharide system by a
combination of 2D NMR COSY and TOCSY experiments, leading
to the identification of one glucopyranosyl unit, one fucopyranosyl
unit, and three rhamnopyranosyl units as the monosaccharides
present in 1. The anomeric configurations for the sugar moieties
were assigned as b for the fucopyranosyl and glucopyranosyl
2 of rhamnoseI (dH 5.92) and dC 173.3 (C-1 of aglycone), respec-
tively. The position of the jalapinolic acid unit was finally deter-
mined by HMBC between jalapinolic acid H-11 (3.85 ppm) and
fucose C-1 (104.3 ppm). These correlations established the struc-
ture of 1 (Chart 1).
The NMR spectra (Tables 1 and 2) of 2 were similar to those of 1,
with the only difference being the location of the trans-cinnamoyl
group. In the HMBC spectrum of 2, the H-2 proton of rhamnoseIII at
d 6.31 showed HMBCs to the carbonyl group at d 166.6 (C-1 of
trans-cinnamoyl), which suggested that the trans-cinnamoyl group
was located at C-2 of rhamnoseIII in 2 rather than at C-3 of rham-
noseIII as in 1. Accordingly, the structure of 2 was established as
shown in Chart 1.
Batatoside J (3), amorphous white powder, gave quasi-molecu-
lar ion at m/z 1343.7816 [M+Na]+ (C71H116O22Na), which was
determined by positive-ion HRESIMS. Basic hydrolysis of it affor-
ded operculinic acid E (11) as the glycosidic acid, and dodecanoic,
decanoic, and trans-cinnamic acids as organic acids. The position of
the jalapinolic acid moiety in the oligosaccharide was determined
by correlation between jalapinolic acid H-11 (3.88 ppm) and glu-
moieties, and
a for the rhamnopyranosyl unit by comparison with
values reported for the corresponding residues in oligosaccha-
rides10,19–21 The interglycosidic connectivities were determined
from the following HMBCs (Fig. 1): C-2 (80.0 ppm) of fucose with
H-1 (5.50 ppm) of rhamnoseI; C-4 (82.1 ppm) of rhamoseI with
H-1 (5.77 ppm) of rhamnoseII; C-4 (80.8 ppm) of rhamnoseII with
H-1 (6.27 ppm) of rhamnoseIII; and C-3 (70.6 ppm) of rhamnoseII
with H-1 (5.05 ppm) of glucose. Specification of the sites of ester
linkages of the respective organic acids and jalapinolic acid was
also obtained by HMBC experiments (Fig. 2). Thus, HMBCs were
detected between H-2 of rhamnoseII (dH 6.33) and dC 176.0 (C-1
of Mba); H-3 of rhamnoseIII (dH 6.00) and dC 166.4 (C-1 of Cna);
H-4 of rhamnoseIII (dH 6.10) and dC 173.4 (C-1 of Dodeca); and H-

Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
469
Table 2
13C NMR (dC) data of compounds 1–9 (C5D5N, 150 MHz)
Position
1
2
3
4
5
6
7
8
9
Fuc-1
104.3
80.0
73.4
72.9
70.8
17.3
104.1
81.0
73.1
72.6
70.6
17.1
104.3
80.3
73.4
73.0
70.8
17.4
104.2
80.1
73.2
72.9
70.8
17.3
2
3
4
5
6
RhaI-1
98.5
73.6
70.6
82.1
68.4
19.1
98.3
73.4
69.2
79.8
68.2
18.9
98.6
73.6
70.6
80.1
68.2
18.9
98.7
73.7
70.3
81.1
68.3
18.8
98.6
73.6
70.6
80.1
68.2
18.9
98.7
73.5
69.6
80.4
70.6
19.3
98.7
73.5
69.6
80.5
70.6
19.3
98.8
73.9
69.9
80.3
68.2
19.5
98.7
74.0
69.6
80.1
68.0
19.4
2
3
4
5
6
RhaII-1
100.3
73.9
70.6
80.8
68.4
19.0
99.6
72.6
77.1
79.8
68.5
18.9
100.2
73.9
70.6
80.8
68.3
19.3
103.4
69.6
79.5
75.6
68.6
19.3
100.2
73.9
70.6
80.8
68.3
19.3
99.0
73.0
79.0
80.3
68.3
18.2
99.3
73.0
79.0
80.2
68.3
18.2
99.1
73.1
79.9
80.3
68.6
18.9
98.9
73.1
79.4
79.4
68.6
18.9
2
3
4
5
6
RhaIII-1
103.3
70.0
72.0
71.6
68.2
18.1
99.4
73.8
68.0
74.8
68.5
17.8
100.2
74.0
68.2
75.2
68.8
18.1
100.1
74.1
68.0
75.0
68.8
17.9
100.2
74.0
68.2
75.2
68.8
18.1
100.1
71.1
73.7
73.5
68.6
18.7
103.6
70.2
73.8
71.6
68.4
17.7
100.3
74.1
68.2
75.2
68.5
18.0
100.1
73.9
68.0
74.8
68.6
18.0
2
3
4
5
6
RhaIV-1
104.6
73.5
72.5
72.2
68.6
18.5
104.8
73.4
72.6
72.5
68.7
18.5
104.8
72.2
72.6
73.5
68.6
18.6
104.2
72.2
72.6
73.5
68.6
18.6
2
3
4
5
6
Glc-1
2
3
4
5
6
Jal-1
2
11
16
105.5
75.2
79.0
71.6
77.9
63.0
173.3
33.4
82.4
14.3
104.9
74.8
77.9
68.6
77.6
62.9
172.8
33.0
82.1
14.0
104.5
81.8
76.6
71.9
78.0
62.9
173.4
34.5
82.8
14.3
104.5
82.0
76.5
72.0
77.9
62.9
173.4
33.4
82.1
14.0
104.5
81.8
76.6
71.9
78.0
62.8
173.3
33.4
82.8
14.3
104.4
81.9
76.4
71.8
77.9
62.7
173.2
34.1
82.7
14.2
104.5
81.9
76.5
72.0
77.9
62.9
173.2
34.3
82.7
14.2
173.0
34.3
82.4
14.3
173.0
34.1
82.2
14.2
Cna-1
2
3
166.4
118.7
145.2
166.6
118.7
145.2
166.4
118.7
145.2
166.5
118.5
145.5
166.4
118.7
145.2
166.5
118.1
146.0
166.4
118.3
145.6
166.8
118.5
145.6
166.7
118.3
145.5
Deca-1
2
10
173.6
34.3
14.3
172.8
34.2
14.2
Dodeca-1
2
12
173.4
34.6
14.2
173.4
34.6
14.2
173.3
34.6
14.3
173.3
34.3
14.3
173.4
34.6
14.2
173.5
33.1
14.2
173.5
34.3
14.3
Iba-1
2
3
30
176.4
34.4
19.4
18.9
175.9
34.3
19.1
19.0
176.6
34.2
18.9
19.1
Mba-1
2
2-CH3
4
176.0
41.2
16.6
11.4
176.2
41.2
16.6
11.4
176.5
41.1
16.9
11.8
176.5
41.1
16.9
11.8
175.3
41.3
16. 7
11.7
175.3
41.5
16.8
11.8
cose C-1 (104.5 ppm) in the HMBC spectrum. The esterification
positions of the oligosaccharide core were also revealed by HMBC
long-range correlations. Thus, an n-dodecanoyl unit was attached
to C-2 of rhamnoseII, a trans-cinnamoyl group was attached to C-
2 of rhamnoseIII, and a decanoyl substituent was located at C-4
of rhamnoseIII. The structure of batatoside J was hence assigned
as 3 (Chart 1).
C66H106O22, 146 mass unit less than 2. Their proton and carbon sig-
nals in the 1H and 13C NMR spectra (Tables 1 and 2) were similar to
those of 2, except for the loss of one unit of 6-deoxyhexose in 4 and
5, which was confirmed by alkaline hydrolysis, providing operculi-
nic acid E and the same organic acids mixture as for 2. The HMBC
spectrum allowed the esterification sites to be established through
the correlations between carbonyl and proton signals of the mono-
saccharides: thus for 4 and 5, a trans-cinnamoyl substituent was
located at C-2 of rhamnoseIII, an n-dodecanoyl residue was as-
signed at C-4 of rhamnoseIII, and the jalapinolic acid unit was ester-
Batatosides K (4) and L (5), obtained as amorphous white pow-
der, displayed quasi-molecular ion at m/z 1273.7097 [M+Na]+ from
positive HRESIMS, corresponding to
a molecular formula of

470
Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
OH
sidic acid present in 6 and 7, and simonic acid B (13) in 8 and 9. The
Fuc
location of the jalapinolic acid moiety in the oligosaccharide core
was determined by the observed HMBC cross-peaks from jalapinolic
acid H-11 to glucose C-1 in 6 and 7, and to fucose C-1 in 8 and 9. The
esterification positions were determined by three-bond correlations
between carbonyl and proton signals of the monosaccharides using
HMBC: thus C-2-OH of rhamnoseII was acylated by an n-dodecanoyl
substituent in 6, 2-methylbutanoyl in 7, isobutanoyl in 8, and n-
decanoyl in 9; C-2-OH of rhamnoseIII was acylated by a trans-cin-
namoyl substituent in 6, 8, and 9; C-3-OH of rhamnoseIII was acyl-
ated by a 2-methylbutanoyl substituent in 6 and by a trans-
cinnamoyl in 7; C-4-OH of rhamnoseIII was acylated by an n-dodec-
anoyl substituent in 8; and C-2-OH of rhamnoseI was esterified by
jalapinolic acid in 6–9. Consequently, the structures of 6–9 were
determined as shown in Chart 1.
O
O
11S
HO
O
Rha
O
O
Rha
O
O
HO
O
Rha
O
O
O
O
O
O
OH
O
O
O
Mba
OH
Dodeca
OH
OH
O
HO
Glc
Cna
Compounds 1–9 were subjected to a cytotoxic assay using laryn-
geal carcinoma (Hep-2) cells. Compounds 5 and 8 showed cytotoxic
1
activities against Hep-2 cells with ED50 value at 3.5
lg/mL and
2.0 g/mL, respectively. Other compounds with ED50 over 20
l
l
g/
Figure 1. Key HMBCs from H to C for batatoside H (1).
mL were considered to be inactive. Compound 4, an isomer of 5, dif-
fered from 5 only in the esterification position of 2-methylbutanoyl;
compounds 8 and 9 share simonic acid B as core with the same ester-
ification sites, two of which were acylated by different organic acids.
Thus, these compounds showed surprisingly large differences in
cytotoxicity in spite of minor structural differences. Similar to cyclic
dextrins, the coexistence of both hydrophobic and hydrophilic sec-
tions and the macrolactone ring in ‘resin glycosides’ were suggested
to help the delivery of compounds or iron across the cell mem-
brane,22–25 leading to various biological activities, which, however,
could hardly explain the sensitivity to structure of this type of com-
pounds. Certainly, additional investigations on the mechanisms of
action of these compounds would be of value.
ified at C-1 of glucose. HMBCs also revealed the differences be-
tween the two compounds: thus for 4, a 2-methylbutanoyl was lo-
cated at C-3 of rhamnoseII, whereas for 5, it was at C-2 of
rhamnoseII. A long-range HMBC cross-peak between jalapinolic
acid H-11 (3.88 ppm) and glucose C-1 (104.5 ppm) was observed,
allowing the position assignment of the jalapinolic acid moiety in
the oligosaccharide. Thus, the structures of batatosides K and L
were assigned to 4 and 5 (Chart 1).
Batatosides M–P (6–9), obtained as amorphous white powder,
gavequasi-molecular ionat m/z 1419.7537[M+Na]+ (C72H116O26Na),
1307.6406 [M+Na]+ (C64H100O26Na), 1389.7557 [M+Na]+
(C71H114O25Na), and 1361.7169 [M+Na]+ (C69H110O25Na), respec-
tively. Alkaline hydrolysis afforded simonic acid A (12) as the glyco-
Sweet potato varied greatly in the content of periderm ‘resin
glycosides’, showing inhibitory effect on the growth of pathogenic
Figure 2. HMBC spectrum in C5D5N of 1.

Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
471
fungi of roots.26 Levels ranged from 0.05% to 10.02% of the peri-
derm dry weight, which could be partly due to stress of the envi-
ronment, such as weed, insects, and disease.
‘Resin glycosides’ content was positively correlated with the
relative inhibition of yellow nutsedge (Cyperus esculentum L.)27
and the developmental time of the diamondback moth larvae,28
while it was negatively correlated with insect damage ratings of
sweet potato breeding clones29 and lifetime fecundity of diamond-
back moth.28
(KBr): 3444, 2928, 1727, 1636, 1137, 1073 cmꢀ1
;
1H and 13C NMR
data (C5D5N): see Tables 1 and 2; ESIMS: m/z 1431 [M+Cl]ꢀ; HRE-
SIMS: calcd for C72H116O26Na [M+Na]+: m/z 1419.7645; found: m/z
1419.7647).
3.3.2. Batatoside I (2)
White amorphous powder, ½a D25
ꢀ33.6 (c 0.5, MeOH); UV
ꢁ
(MeOH): kmax (log e): 280(4.33), 217 (4.18), 205 (4.16) nm; IR mmax
(KBr): 3450, 2929, 1724, 1636, 1136, 1070 cmꢀ1 1H and 13C NMR
;
Therefore, these ‘resin glycosides’ may be stored as allelochemicals,
contributing to disease resistance and allelopathy of sweet potato.
data (C5D5N): see Tables 1 and 2; ESIMS: m/z 1431 [M+Cl]ꢀ; HRE-
SIMS: calcd for C72H116O26Na [M+Na]+: m/z 1419.7647; found: m/z
1419.7675.
3. Experimental
3.3.3. Batatoside J (3)
White amorphous powder, ½a D25
ꢀ20.8 (c 0.4, MeOH); UV
ꢁ
3.1. General procedures
(MeOH): kmax (log e): 279 (4.17), 217 (3.99), 205 (4.07) nm; IR mmax
(KBr): 3444, 2927, 1736, 1638, 1134, 1056 cmꢀ1 1H and 13C NMR
;
1H, 13C, and 2D NMR spectra were recorded on a Bruker ACF-
600 spectrometer (600 MHz and 150 MHz, respectively) with
TMS as internal standard. Mass spectra were obtained on a MS Agi-
lent 1100 series LC/MSD ion trap mass spectrometer (ESIMS), an
Agilent TOF MSD 1946D spectrometer, and positive-ion HR-ESIMS
were recorded with an Agilent TOF MSD 1946D spectrometer. UV
spectra were obtained on a Shimadzu UV-2501PC spectrophotom-
eter. The IR (KBr) spectra were obtained on a Nicolet Impact 410
spectrometer. HPLC separations were performed on an Agilent
data (C5D5N): see Tables 1 and 2; ESIMS: m/z 1343 [M+Na]+; HRE-
SIMS: calcd for C71H116O22Na [M+Na]+: m/z 1343.7850; found: m/z
1343.7816.
3.3.4. Batatoside K (4)
White amorphous powder, ½a D25
ꢀ22.3 (c 0.4, MeOH); UV
ꢁ
(MeOH): kmax (log e): 281 (4.15), 217 (3.99), 204 (3.95) nm; IR mmax
(KBr): 3444, 2927, 1736, 1638, 1134, 1056 cmꢀ1 1H and 13C NMR
;
data (C5D5N): see Tables 1 and 2; ESIMS: m/z 1285 [M+Cl]ꢀ; HRE-
SIMS: calcd for C66H106O22Na [M+Na]+: m/z 1273.7067; found: m/z
1273.7097.
1100 series instrument with
a Shim-park RP-C18 column
(200 ꢂ 20 mm i.d.) and UV detector at 280 nm. GC-MS was run
on a Varian CP-3800 instrument. Optical rotations were measured
with a JASCO P-1020 polarimeter in MeOH solution. TLC was per-
formed on pre-coated Silica Gel 60 F254 (Qingdao Marine Chemical
Co. Ltd) and detected by spraying with 10% H2SO4–EtOH. Column
chromatography was carried out with Silica Gel H (Qingdao Marine
3.3.5. Batatoside L (5)
White amorphous powder, ½a D25
ꢀ29.6 (c 0.4, MeOH); UV
ꢁ
(MeOH) kmax (log e): 281 (3.94), 217 (3.79), 204 (3.77) nm; IR mmax
(KBr): 3444, 2927, 1725, 1637, 1136, 1055 cmꢀ1 1H and 13C NMR
;
data (C5D5N): see Tables 1 and 2; ESIMS: m/z 1249 [MꢀH]ꢀ; HRE-
SIMS: calcd for C66H106O22Na [M+Na]+: m/z 1273.7067; found: m/z
1273.7097.
Chemical Co. Ltd), Sephadex LH-20 (20–100
ODS-C18 (100–200 m, Waters).
lm, Pharmacia), and
l
3.2. Plant material
3.3.6. Batatoside M (6)
White amorphous powder, ½a D25
ꢀ36.4 (c 0.4, MeOH); UV
ꢁ
The tubers of I. batatas were collected in Yanlin County, Hunan,
China, in September 2004. The plant material was identified by
Prof. Min-Jian Qin, and a voucher specimen (No. 040912) was
deposited in the Department of Natural Medicinal Chemistry, Chi-
na Pharmaceutical University.
(MeOH): kmax (log e): 280 (4.28), 217 (4.38), 204 (4.28) nm; IR mmax
(KBr): 3450, 2932, 1736, 1638, 1139, 1060 cmꢀ1 13C and 1H NMR
;
data (C5D5N): see Tables 2 and 3; ESIMS: m/z 1395 [MꢀH]ꢀ; HRE-
SIMS: calcd for C72H116O26Na [M+Na]+: m/z 1419.7647; found: m/z
1419.7537.
3.3. Isolation of resin glycosides
3.3.7. Batatoside N (7)
White amorphous powder, ½a D25
ꢀ32.5 (c 0.5, MeOH); UV
ꢁ
To obtain more resin glycosides, we collected 50 kg of I. batatas,
which was extracted with 95% EtOH (3 ꢂ 20 L ꢂ 2 h) at 80 °C, the
extract soln was concentrated under diminished pressure, and al-
lowed to stand overnight so as to fully precipitate the starch. The
supernatant soln was further concentrated to produce a residue,
which was partitioned between chloroform (5 ꢂ 0.5 L) and water
(0.5 L) to give 130 g and 50 g of extracts from these two layers,
respectively. The chloroform extract was chromatographed over
silica gel and eluted with a gradient CHCl3–MeOH, and then sub-
mitted to RP-C18 column chromatography to afford three fractions.
Further purified by successive RP-18 preparative HPLC eluted with
90% MeOH, Fraction 1 gave 12.7 mg 6 at tR 6.44 min, 16.5 mg 7 at tR
8.91 min, and 15.6 mg 9 at tR 5.91 min; with 96% MeOH, Fraction 2
afforded 8.7 mg 4 at tR 5.36 min and 26.0 mg 5 at tR 7.91 min; with
98% MeOH, Fraction 3 gave 38.5 mg 1 at tR 26.5 min, 9.24 mg 2 at tR
27.7 min, 10.4 mg 3 at tR 34.5 min, and 20.3 mg 8 at tR 21.4 min.
(MeOH): kmax (log e): 280 (4.16), 217 (4.00), 205 (3.98) nm; IR mmax
(KBr): 3444, 2932, 1730, 1635, 1135, 1053 cmꢀ1 13C and 1H NMR
;
data (C5D5N): see Tables 2 and 3; ESIMS: m/z 1283 [MꢀH]ꢀ; HRE-
SIMS: calcd for C65H102O25Na [M+Na]+: m/z 1307.6395; found: m/z
1307.6406.
3.3.8. Batatoside O (8)
White amorphous powder, ½a D25
ꢀ26.4 (c 0.6, MeOH); UV
ꢁ
(MeOH): kmax (log e): 280 (4.25), 217 (4.09), 206 (4.12) nm; IR mmax
(KBr): 3446, 2930, 1724, 1635, 1132, 1070 cmꢀ1 13C and 1H NMR
;
data (C5D5N): see Tables 2 and 3; ESIMS: m/z 1365 [MꢀH]ꢀ; HRE-
SIMS: calcd for C71H114O25Na [M+Na]+: m/z 1389.7541; found: m/z
1389.7557.
3.3.9. Batatoside P (9)
White amorphous powder, ½a D25
ꢀ30.6 (c 0.4, MeOH); UV
ꢁ
3.3.1. Batatoside H (1)
(MeOH): kmax (log e): 280 (4.10), 217 (4.02), 205 (4.08) nm; IR mmax
White amorphous powder, ½a D25
ꢀ13.2 (c 0.3, MeOH); UV
ꢁ
(KBr): 3452, 2929, 1739, 1638, 1135, 1051 cmꢀ1
;
13C and 1H NMR
data (C5D5N): see Tables 2 and 3; ESIMS: m/z 1373 [M+Cl]ꢀ; HRE-
(MeOH): kmax (log e): 280 (4.21), 217 (4.06), 205 (4.04) nm; IR mmax

472
Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
Table 3
1H [dY (J, Hz)] data of compounds 6–9 (C5D5N, 600 MHz)
Positionb
6
7
8
9
Glc-1
4.94 (d, 7.6)
3.88a
4.18 (t, 8.9)
4.13 (t, 8.9)
3.85a
4.76 (d, 7.6)
3.88a
4.18 (t, 8.9)
4.13 (t, 8.9)
3.85a
2
3
4
5
6
4.35 (dd, 5.1, 11.5)
4.41 (dd, 2.8, 11.5)
4.35 (dd, 5.1, 11.5)
4.41 (dd, 2.2, 11.5)
Fuc-1
4.75 (d, 7.5)
4.72 (d, 7.5)
2
3
4
5
6
4.16 (dd, 7.5, 9.4)
4.08 (dd, 9.4, 3.5)
3.98 (d, 3.5)
3.77 (q, 6.4)
1.50 (d, 6.4)
4.15 (dd, 7.5, 9.4)
4.07 (dd, 9.4, 3.5)
3.98 (d, 3.5)
3.76 (q, 6.4)
1.49 (d, 6.4)
RhaI-1
5.60 (br s)
5.49 (br s)
5.47 (br s)
5.47 (br s)
2
3
4
5
6
6.06 (br s)
5.07 (dd, 3.2, 9.0)
4.20 (t, 9.0)
4.42 (dq, 9.0, 6.0)
1.57 (d, 6.0)
6.06 (br s)
5.07 (dd, 3.2, 9.0)
4.24 (t, 9.0)
4.36 (dq, 9.0, 6.2)
1.57 (d, 6.2)
5.96 (br s)
5.94 (br s)
5.01 (dd, 3.2, 9.5)
4.21 (t, 9.5)
4.44 (dq, 9.5, 6.1)
1.62 (d, 6.1)
5.01(dd, 3.2, 9.5)
4.21(t, 9.5)
4.44 (m)
1.62 (d, 6.1)
RhaII-1
6.06 (br s)
6.09 (br s)
6.11 (br s)
6.14 (br s)
2
3
4
5
6
6.00 (br s)
4.63 (dd, 3.2, 9.2)
4.35 (t, 9.2)
4.49 (dq, 9.2, 6.2)
1.73 (d, 6.2)
5.97 (br s)
4.66 (dd, 3.2, 9.2)
4.28 (t, 9.2)
4.49 (dq, 9.2, 6.2)
1.63 (d, 6.2)
5.99 (br s)
4.65 (dd, 3.0, 9.1)
4.32 (t, 9.1)
4.37 (dq, 9.1, 5.8)
1.67 (d, 5.8)
6.01 (br s)
4.61 (dd, 3.0, 9.3)
4.34 (t, 9.3)
4.44 (dq, 9.3, 5.8)
1.65 (d, 5.8)
RhaIII-1
5.91 (br s)
5.96 (br s)
5.94 (br s)
5.81 (br s)
2
3
4
5
6
6.17 (br s)
5.94 (dd, 3.2, 9.3)
4.35 (t, 9.3)
4.45 (dq, 9.3, 6.0)
1.57 (d, 6.0)
4.94 (br s)
5.90 (dd, 3.2, 9.3)
6.02 (t, 9.3)
4.39 (dq, 9.3, 6.3)
1.40 (d, 6.3)
6.04 (br s)
4.68 (dd, 3.0, 9.8)
5.78 (t, 9.8)
4.40 (dq, 9.8, 6.1)
1.65 (d, 6.1)
6.01 (br s)
4.68 (dd, 3.0, 9.4)
5.72 (t, 9.4)
4.34 (dq, 9.4, 6.1)
1.65 (d, 6.1)
RhaIV-1
5.60 (br s)
4.72 (br s)
4.44a
4.20 (t, 9.3)
4.30 (dq, 9.3, 6.0)
1.60 (d, 6.0)
5.71 (br s)
4.77 (br s)
4.44a
4.20 (t, 9.3)
4.39 (dq, 9.3, 6.0)
1.40 (d, 6.0)
5.85 (br s)
4.78 (br s)
4.39 (dd, 3.3, 9.0)
4.19 (t, 9.0)
4.26 (dq, 9.0, 5.9)
1.54 (d, 5.9)
5.67 (br s)
4.78 (br s)
4.39 (dd, 3.3, 9.0)
4.19 (t, 9.0)
4.26 (dq, 9.0, 6.4)
1.48 (d, 6.4)
2
3
4
5
6
Ag-2
2.25 (m)
2.38 (m)
3.87 (m)
0.84 (t, 7.0)
2.23 (m)
2.37 (m)
3.87 (m)
0.80 (t, 7.0)
1.91 (m)
2.23 (m)
3.85 (m)
0.89 (t, 6.7)
2.24 (m)
2.38 (m)
3.85 (m)
0.84 (t, 6.7)
11
16
Cna-2
3
6.83 (d, 16.0)
7.92 (d, 16.0)
6.51 (d, 16.0)
7.79 (d, 16.0)
6.55 (d, 15.9)
7.76 (d, 15.9)
6.52 (d, 15.9)
7.74 (d, 15.9)
Deca-2
10
2.31 (t, 7.0)
0.82 (t, 7.2)
Dodeca-2
12
2.42 (m)
0.84 (t, 7.0)
2.34 (t, 7.0)
1.11 (t, 7.2)
Iba-2
2.60 (m)
2.40a
2.62 (m)
3
30
1.10 (d, 5.9)
1.09 (d, 7.5)
1.07 (d, 7.0)
1.16 (d, 7.0)
1.16 (d, 7.0)
1.19 (d, 7.0)
Mba-2
2-CH3
4
2.35 (m)
1.09 (d, 7.0)
0.85 (t, 7.0)
2.34 (m)
1.05 (d, 7.0)
0.83 (t, 7.0)
a
Signal pattern unclear due to overlapping.
SIMS: calcd for C69H110O25Na [M+Na]+: m/z 1361.7228; found: m/z
1361.7169.
model 2200 mass spectrometer (Varian) in EI at 70 eV under the
following conditions: 30 m ꢂ 0.25 mm i.d., 0.25 m, VF-5 ms capil-
lary column (Varian); column temperature, 160–240 °C tempera-
ture programmed at 10 °C/min; carrier gas, N2 (30 mL/min).
3.4. Hydrolysis
3.4.1. Alkaline hydrolysis and determination of organic acids
Compounds 1–9 (3 mg each) in 5% KOH (3 mL) were refluxed at
90 °C for 2 h separately. The reaction mixtures were acidified to pH
4 and extracted with ether (30 mL). The ether layer was washed
with water, dried over anhyd Na2SO4, and esterified with MeOH
using 0.5 N H2SO4 as catalyst. The methyl esters were analyzed
by GC–MS on a model 3800 gas chromatograph interfaced with a
3.4.2. Acid hydrolysis and sugar analysis
After extraction with ether, the alkaline hydrolysate of 1–9 was
further partitioned with n-BuOH (30.0 mL) to afford glycosidic acids
(10–13), which were evaporated to dryness and hydrolyzed by 1 N
H2SO4 in 4 mL THF under reflux for 4 h. The hydrolysate was cooled
to room temperature and extracted three times with ether and then
reacted with an excess of diazomethane to furnish 11-hydroxyhexa-

Y.-Q. Yin et al. / Carbohydrate Research 344 (2009) 466–473
473
decanoic acid methyl ester (14). The aq layer was neutralized by
Acknowledgments
passing through an ion-exchange resin (Amberlite MB-3) column
and was extracted with n-BuOH, and then concentrated to yield a
saccharide residue. An aliquot of this residue was subjected to silica
This research work was supported by the National Natural Sci-
ence Foundation of China (No. 30472144) and the Cultivation Fund
of the Key Scientific and Technical Innovation Project, Ministry of
Education of China (707033). We acknowledge Dr. Bing Ma, Shan-
dong University, for measuring the TOCSY, HMQC, and HMBC NMR
spectra.
gel chromatography (6:4:1 CHCl3–MeOH–H2O) to give
D
-fucose:
½
a 2D5
ꢁ
+66.4 (c 0.8, water);
L
-rhamnose: ½a 2D5
ꢁ
ꢀ9.7 (c 1.0, water); and
D
-glucose: ½a 2D5
ꢁ
+100.0 (c 1.0, water). Another aliquot was treated
with water (0.05 mL) and pyridine (0.03 mL) at 60 °C for 1 h with
stirring. After the solvent was evaporated and the reaction mixture
was dried, pyridine (0.5 mL), hexamethyldisilazane (0.8 mL), and
trimethylsilyl chloride (0.4 mL) were added to the residue. The reac-
tion mixture was heated at 60 °C for 30 min. Under the same condi-
tions as mentioned in Section 3.4.1, the supernatant was identified
Supplementary data
Supplementary data (HRESIMS, 1H- and 13C NMR spectra) of
compounds 1–9. Supplementary data associated with this article
can be found, in the online version, at doi:10.1016/
j.carres.2008.12.022.
by GC–MS; the presence of D-fucose, L-rhamnose, and D-glucose
was confirmed by comparison of the retention times of their TMSi
derivatives with those of standard sugar derivatives prepared in a
similar way, which showed retention times of 4.57 min, 5.09 min,
and 8.03 min, respectively.
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To compound 14 (2.0 mg, in 1.5 mL of CH2Cl2) was added a soln
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For selected
D
d values [d(R) ꢀ d(S)], see Scheme 1.
3.5.1. 11S-hydroxyhexadecanoic acid methyl ester (14)
Colorless oil (CHCl3), ½a D25
ꢁ
+1.1 (c 0.2, CHCl3); IR mmax (KBr):
3333, 2920, 2850, 1207 cmꢀ1
;
1H NMR (600 MHz, CDCl3): dH 3.67
(s, 3, OCH3), 3.58 (m, 1H, OCH-11), 2.30 (t, 2H, J 7.5 Hz, OCOCH2-
2), 1.62 (t, 2H, J 7.0, CH2-10), 1.44 (m, 2H, CH2-12), 0.89 (t, 3H, J
6.9 Hz, CH3-16); ESITOF-MS: m/z 309 [M+Na]+.
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3.5.2. 11-(R-MPA)-hydroxyhexadecanoic acid methyl ester (15)
Colorless oil (CHCl3), ½a D25
ꢁ
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3442, 2927, 2855, 1743, 1261, 802 cmꢀ1
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OCH-11), 4.73 (s, 1H, OCH), 3.67 (s, 3H, OCH3), 3.41 (s, 3H,
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457 [M+Na]+; 435 [M+H]+.
3.5.3. 11-(S-MPA)-hydroxyhexadecanoic acid methyl ester (16)
Colorless oil (CHCl3), ½a D25
ꢁ
+1.4 (c 0.20, CHCl3); IR mmax (KBr):
3453, 2961, 2926, 2852, 1742, 1261 cmꢀ1
;
1H NMR (600 MHz,
CDCl3): dH 7.44 (m, 2H, C6H2), 7.34 (m, 3H, C6H3), 4.90 (m, 1H,
OCH-11), 4.73 (s, 1H, OCH), 3.67 (s, 3H, OCH3), 3.41 (s, 3H,
OCH3), 2.30 (t, 2H, J 7.6 Hz, OCOCH2-2), 1.61 (m, 2H, CH2-10),
1.54 (m, 2H, CH2-12), 0.84 (t, 3H, J 7.1 Hz, CH3-16); ESIMS: m/z
457 [M + Na]+.
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3.6. Cytotoxic activity assays
The assay of cytotoxic activity against laryngeal carcinoma
(Hep-2) cells of compounds 1–9 was performed according to the
published method34 using vinblastine as positive control with an
ED50 value at 0.004 lg/mL.