Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties

Abstract

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural–activity relationships (SARs) of sea cucumber glycosides are also discussed briefly.

Full text

marine drugs
Review
Sea Cucumber Glycosides: Chemical Structures,
Producing Species and Important
Biological Properties
Muhammad Abdul Mojid Mondol 1, Hee Jae Shin 2, *, M. Aminur Rahman 3
and Mohamad Tofazzal Islam 4,*
1School of Science and Technology, Bangladesh Open University, Board Bazar, Gazipur 1705, Bangladesh;
drmojidmondol@gmail.com
2Marine Natural Products Laboratory, Korea Institute of Ocean Science and Technology, 787 Haeanro,
Ansan 427-744, Korea
3
World Fisheries University Pilot Programme, Pukyong National University (PKNU), 45 Yongso-ro, Nam-gu,
Busan 48513, Korea; aminur1963@gmail.com
4Department of Biotechnology, Bangabandhu Sheikh Mujibur Rahman Agricultural University,
Gazipur 1706, Bangladesh
*Correspondence: shinhj@kiost.ac.kr (H.J.S.); tofazzalislam@yahoo.com (M.T.I.);
Tel.: +82-31-400-6172 (H.J.S.); +880-2920-5310-14 (ext. 2252) (M.T.I.);
Fax: +82-31-400-6170 (H.J.S.); +880-2920-5333 (M.T.I.)
Received: 27 June 2017; Accepted: 11 October 2017; Published: 17 October 2017
Abstract:
Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and
other Asian countries. They produce abundant biologically active triterpene glycosides. More than
300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers,
which are classified as holostane and nonholostane depending on the presence or absence of a specific
structural unit
γ
(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain
up to six monosaccharide units mainly consisting of D-xylose, 3-O-methy-D-xylose, D-glucose,
3-O-methyl-D-glucose, and D-quinovose. Cytotoxicity is the common biological property of
triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also
exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our
understanding on diverse chemical structures of triterpene glycosides from various species of sea
cucumbers and their important biological activities. Mechanisms of action and structural–activity
relationships (SARs) of sea cucumber glycosides are also discussed briefly.
Keywords: holostane; nonholostane; cucumarioside; cytotoxic; antifungal; glycosides
1. Introduction
Nature is the largest source of pharmaceutical lead drugs for the remedies of many diseases.
Earlier scientists mainly focused on terrestrial samples (plants and microorganisms) for the discovery
of lead bioactive compounds. With the passage of time, the search for new drugs or agrochemicals has
been switching from land to ocean due to re-isolation of known natural products from terrestrial
samples. Marine organisms produce diversified bioactive compounds because of large species
biodiversities and living in extremely harsh environment.
Among so many sources, numerous bioactive metabolites have been isolated from marine
invertebrates such as echinoderms with a broad spectrum of biological activities [
1
]. The echinoderms
are divided into five classes, i.e., Holothuroidea (sea cucumbers), Asteroidea (starfishes), Echinoidea
(sea urchins), Crinoidea (sea lilies), and Ophiuroidea (brittle stars and basket stars), which live
exclusively in the marine habitat, distributed in almost all depths and latitudes, as well as reef
Mar. Drugs 2017,15, 317; doi:10.3390/md15100317 www.mdpi.com/journal/marinedrugs

Mar. Drugs 2017,15, 317 2 of 35
environments or shallow shores [
2
,
3
]. The importance of these echinoderms as a potential source
of bioactive compounds for the development of new therapeutic drugs/agrochemicals has been
growing rapidly [
1
]. Compounds isolated from echinoderms showed numerous biological activities
including antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, anti-tuberculosis,
anti-inflammatory, antitumor, and antiviral activities [1].
Sea cucumber traditionally has been used as tonic food in China and other Asian countries
for thousands of years. Besides being used as food, sea cucumbers are also promising source
of bioactive natural products which predominantly belong to triterpene glycosides exhibiting
antifungal, cytotoxic, hemolytic, cytostatic, and immunomodulatory and antiviral activities [
4
]. Several
monographs concerning the structures and biological properties of triterpene glycosides obtained
from sea cucumbers have been published but not presented in a systematic way [
5
,
6
]. This report
comprehensively reviews in depth structural features of sea cucumber glycosides with corresponding
producing species. Important biological activities, mechanism of action, and structure–activity
relationships (SARs) of the diverse glycosides produced by the different species of sea cucumber
are also discussed briefly.
2. Taxonomy, Distribution and Nutritive Value of Sea Cucumbers
One of the predominant invertebrate lives in marine environment is sea cucumber, which belong to
the class Holothuroidea under the phylum Echinodermata. Holothuroidea has been divided into three
subclasses, Aspidochirotacea, Apodacea and Dendrochirotacea, and further into six orders, Apodida,
Elasipodida, Aspidochirotida, Molpadida, Dendrochirotida and Dactylochirotida [
7
]. Majority of the
harvestable species of sea cucumbers belong to three families, viz., Holothuriidae (genera Holothuria
and Bohadschia), Stichopodidae (genera Stichopus,Actinopyga,Thelenota,Parastichopus and Isostichopus),
and Cucumariidae (genus Cucumaria) [8].
Sea cucumbers are elongated tubular or flattened soft-bodied marine benthic invertebrates,
typically with leathery skin, ranging in length from a few millimeters to a meter [
9
]. Holothuroids
encompass 14,000 known species occur in most benthic marine habitats worldwide, in both temperate
and tropical oceans, and from the intertidal zone to the deep sea, and are considered as the very
important parts of oceanic ecosystem [10].
Economically, sea cucumbers are important in two reasons: first, some species produce triterpene
glycosides that are interested to pharmaceutical companies finding their medical use and second, use
as food item. About 70 species of sea cucumbers have been exploited worldwide; out of which
11 species have been found to be commercially important [
11
]. Sea cucumbers have been well
recognized as a tonic and traditional remedy in Chinese and Malaysian literature for their effectiveness
against hypertension, asthma, rheumatism, cuts and burns, impotency and constipation [
12
,
13
].
Nutritionally, sea cucumbers have an impressive profile of valuable nutrients such as vitamin A,
vitamin B
1
(thiamine),vitamin B
2
(riboflavin), vitamin B
3
(niacin), and minerals, especially calcium,
magnesium, iron and zinc [14,15].
3. Extraction, Purification and Characterization
To extract glycosides, first sea cucumbers will be freeze dried, then cut into pieces and extracted
twice with refluxing EtOH. The combined extracts will be concentrated under reduced temperature
and the residue will be dissolved in H
2
O. Desalting will be carried out by passing this fraction through
a Polychrom column (Teflon), eluting first the inorganic salts and crude polar impurities with H
2
O and
then the glycosides fraction with 50% EtOH. The fraction will be sub-fractionated by silica gel column
chromatography using suitable gradient solvent system. The glycosides from each sub-fraction can be
purified by reverse phase HPLC developing suitable solvent system (MeOH-H2O).
Triterpene glycosides have two parts: carbohydrate and triterpene. The number of monosaccharide
units present in the carbohydrate chain can be deduced by observing the number of anomeric carbons
(~103 ppm) and protons (~5 ppm, d) resonances in
13
C and
1
H NMR spectra, respectively. The sequence

Mar. Drugs 2017,15, 317 3 of 35
of monosaccharide units in the carbohydrate chain can be established by the analysis of anomeric
H/C correlations in the HMBC spectrum which can also be confirmed by NOE corrections between
anomeric protons and MALDI-TOF mass spectroscopic data analysis. The position of attachment of
glycone with aglycone can be confirmed by the HMBC experiment.
The presence of diverse types of monosaccharide units and their repetitions in the carbohydrate
chain can be established by acid hydrolysis followed by GC-MS analysis of the corresponding
aldononitrile peracetates [
16
]. The site of attachment of sulfate group at monosaccharide units can
be determined by observing chemical shift of esterification carbon atoms. The chemical shifts of
α
(esterification) and
β
-carbons are shifted ~5 ppm downfield and ~2 ppm up field, respectively, compare
to their corresponding nonsulfated derivatives.
The structure of the aglycone can be established based on its spectroscopic data (
1
H NMR,
13
C NMR, COSY, HMBC, HSQC, and TOCSY) and by comparing with the literature data. Configuration
can be determined by the analysis of NOE data, stable conformers, coupling constants and comparing
chemical shifts of chiral centers with literature.
4. Structural Features of Triterpene Glycosides Isolated from Sea Cucumbers
Triterpene glycosides, also known as holothurins or saponins, are secondary metabolites typically
produced by sea cucumbers (class Holothuroidea). These glycosides are amphiphilic in nature
having two parts: aglycone (lipophilic, lipid-soluble) and glycone (hydrophilic, water-soluble).
The majority of the glycosides contain so called holostane type aglycone comprise of lanostane-3β-ol
with a
γ
(18,20)-lactone in the E-ring of the pentacyclic triterpene [(3
β
,20S-dihydroxy-5
α
-lanostano-
γ
(18,20)-lactone] (Figure 1). A few of the glycosides contain nonholostane type aglycone which do not
have γ(18,20)-lactone in the tetracyclic triterpene.
The glycone parts may contain up to six monosaccharide units covalently connected to C-3 of
the aglycone. The sugar moieties mainly consist of D-xylose (Xyl), D-quinovose (Qui), D-glucose
(Glc), 3-O-methyl-D-glucose (MeGlc), 3-O-methyl-D-xylose (MeXyl) (Figure 2) and sometimes
3-O-methyl-D-quinovose (MeQui), 3-O-methyl-D-glucuronic acid (MeGlcA) and 6-O-acetyl-D-glucose
(AcGlc). In the carbohydrate chain, the first sugar unit is always a xylose and a majority case second
is quinovose, whereas 3-O-methyl-D-glucose and/or 3-O-methyl-D-xylose are always the terminal
monosaccharide units. The presence of two quinovose residues in a carbohydrate chain is unique for
sea cucumber and starfish glycosides.
In glycone part, the sugar units are generally arranged in a straight or branched chain
(Figure 3). The majority of tetrasaccharides show a linear chain with the most common
3-O-Me-Glc-(1
→
3)-Glc-(1
→
4)-Qui-(1
→
2)-Xyl. Hexaglycosides are generally nonsulfated with a linear
3-O-Me-Glc (1
→
3)-Glc (1
→
4)-Xyl (2
→
1)-Qui (4
→
1)-Glc (3
→
1)-3-O-MeGlc unit. Pentasaccharides
have a linear chain like tetrasaccharides but a branching at C-2 of quinovose (Figure 3).
Sixty percent of the triterpene glycosides isolated so far from sea cucumbers have sulfate groups
linked to the monosaccharide units of the carbohydrate chain. Most of them are monosulfsated,
but many di- and trisulfated glycosides have also been isolated. Most tetrasaccharides and
pentasaccharides are sulfated at C-4 of xylose unit. In both the cases, additional sulfate groups
at C-6 of the 3-O-methylglucose and glucose units have also been found. The term “Ds” stands for
desulfated. Sea cucumber triterpene glycosides are chemotaxonomic markers specific for groups of
genera within each family.

Mar. Drugs 2017,15, 317 4 of 35
Mar. Drugs 2017, 15, 317 3 of 35
the analysis of anomeric H/C correlations in the HMBC spectrum which can also be confirmed by
NOE corrections between anomeric protons and MALDI-TOF mass spectroscopic data analysis. The
position of attachment of glycone with aglycone can be confirmed by the HMBC experiment.
The presence of diverse types of monosaccharide units and their repetitions in the carbohydrate
chain can be established by acid hydrolysis followed by GC-MS analysis of the corresponding
aldononitrile peracetates [16]. The site of attachment of sulfate group at monosaccharide units can be
determined by observing chemical shift of esterification carbon atoms. The chemical shifts of α
(esterification) and β-carbons are shifted ~5 ppm downfield and ~2 ppm up field, respectively,
compare to their corresponding nonsulfated derivatives.
The structure of the aglycone can be established based on its spectroscopic data (1H NMR, 13C
NMR, COSY, HMBC, HSQC, and TOCSY) and by comparing with the literature data. Configuration
can be determined by the analysis of NOE data, stable conformers, coupling constants and
comparing chemical shifts of chiral centers with literature.
4. Structural Features of Triterpene Glycosides Isolated from Sea Cucumbers
Triterpene glycosides, also known as holothurins or saponins, are secondary metabolites
typically produced by sea cucumbers (class Holothuroidea). These glycosides are amphiphilic in
nature having two parts: aglycone (lipophilic, lipid-soluble) and glycone (hydrophilic,
water-soluble). The majority of the glycosides contain so called holostane type aglycone comprise of
lanostane-3β-ol with a γ(18,20)-lactone in the E-ring of the pentacyclic triterpene
[(3β,20S-dihydroxy-5α-lanostano- γ(18,20)-lactone] (Figure 1). A few of the glycosides contain
nonholostane type aglycone which do not have γ(18,20)-lactone in the tetracyclic triterpene.
The glycone parts may contain up to six monosaccharide units covalently connected to C-3 of
the aglycone. The sugar moieties mainly consist of D-xylose (Xyl), D-quinovose (Qui), D-glucose
(Glc), 3-O-methyl-D-glucose (MeGlc), 3-O-methyl-D-xylose (MeXyl) (Figure 2) and sometimes
3-O-methyl-D-quinovose (MeQui), 3-O-methyl-D-glucuronic acid (MeGlcA) and
6-O-acetyl-D-glucose (AcGlc). In the carbohydrate chain, the first sugar unit is always a xylose and a
majority case second is quinovose, whereas 3-O-methyl-D-glucose and/or 3-O-methyl-D-xylose are
always the terminal monosaccharide units. The presence of two quinovose residues in a
carbohydrate chain is unique for sea cucumber and starfish glycosides.
In glycone part, the sugar units are generally arranged in a straight or branched chain (Figure
3). The majority of tetrasaccharides show a linear chain with the most common
3-O-Me-Glc-(1→3)-Glc-(1→4)-Qui-(1→2)-Xyl. Hexaglycosides are generally nonsulfated with a linear
3-O-Me-Glc (1→3)-Glc (1→4)-Xyl (2→1)-Qui (4→1)-Glc (3→1)-3-O-MeGlc unit. Pentasaccharides have
a linear chain like tetrasaccharides but a branching at C-2 of quinovose (Figure 3).
Sixty percent of the triterpene glycosides isolated so far from sea cucumbers have sulfate
groups linked to the monosaccharide units of the carbohydrate chain. Most of them are
monosulfsated, but many di- and trisulfated glycosides have also been isolated. Most
tetrasaccharides and pentasaccharides are sulfated at C-4 of xylose unit. In both the cases, additional
sulfate groups at C-6 of the 3-O-methylglucose and glucose units have also been found. The term
“Ds” stands for desulfated. Sea cucumber triterpene glycosides are chemotaxonomic markers
specific for groups of genera within each family.
Figure 1. Structures of lanostane, holostane and holostanol.
H
H
H
H
1
4
6
8
9
10
11 13
14
17
18
19
20
21 22
25
26
27
30 31
32
5α-lanostane
H
H
H
1
4
6
8
9
10
11 13
19
30 31
32
20S-hydroxy-5α-lanostano-γ(18,20)-lactone
(Holostane)
O
O
3
16
17
20
21
23 25
26
18
27
H
H
H
1
4
6
8
9
10
11 13
19
30 31
32
3β,20S-dihydroxy-5α-lanostano-γ(18,20)-lactone
(Holostanol)
O
O
3
16
17
20
21
23 25
26
18
27
HO
AB
CD
E
Figure 1. Structures of lanostane, holostane and holostanol.
Mar. Drugs 2017, 15, 317 4 of 35
Figure 2. Common sugar units present in sea cucumber glycosides.
Figure 3. Some common carbohydrate architectures found in sea cucumber glycosides.
Triterpene glycosides can be classified as holostane type having 3β-hydroxy-5α-lanostano-
γ(18,20)-lactone structural feature and nonholostane type do not have a γ(18,20)-lactone but have
other structural features like holostane type glycosides.
4.1. Holostane Type Triterpene Glycosides
Depending on the position of double bond in the B and C ring of the aglycone (Figure 1),
holostane type glycosides can be further subdivided into three groups: glycosides with
3β-hydroxyholost-7(8)-ene, 3β-hydroxyholost-9(11)-ene, and 3β-hydroxyholost-8(9)-ene aglycone
skeletons. There are eight pentacyclic triterpene and 30 alkane side chain aglycone architectures
commonly found in holostane type glycosides (Figure 4). In these architectures, certain functional
groups are generally attached to the specific carbons: keto and β-acetoxy groups at C-16, and
α-hydroxy group at C-12 and C-17.
(a)
O
HO
MeO OH
O
HO
OH
HO
OH
HO
D-glucose
HO
OH
3-O-methyl-D-glucose
O
HO
HO OH
OH
D-xylose
O
HO
MeO OH
OH
3-O-methyl-D-xylose
O
HO
HO OH
OH
D-quinovose
O
O
HO O
O
HO
OH
HO
O
HO
MeO OH
HO
O
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
O
HO O
O
HO
OH
HO
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
HO
O
HO
HO O
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
HO
HO O
O
O
HO
O
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
O
HO O
O
HO
OH
HO
O
HO
HO OH
O
HO
O
HO
HO O
O
HO
HO OH
O
O
HO
HO OH
O
HO
HO O
OH
1
2
3
4
5
61
2
3
4
5
1
2
3
4
1
2
1
2
3
1
2
3
4
5
Xyl
Glc
MeGlc
Qui
Glc
MeGlc
O
O
O
O
O
O
O
OAc
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
HO HO
OH
1
46
8
9
10
11 13
30 31
32
3
16
17
20
21
18
HO
OH
O
HO
III III IV
VVI VII VIII
Sugar Sugar Sugar Sugar
Sugar Sugar Sugar Sugar
OH
OAc
Figure 2. Common sugar units present in sea cucumber glycosides.
Mar. Drugs 2017, 15, 317 4 of 35
Figure 2. Common sugar units present in sea cucumber glycosides.
Figure 3. Some common carbohydrate architectures found in sea cucumber glycosides.
Triterpene glycosides can be classified as holostane type having 3β-hydroxy-5α-lanostano-
γ(18,20)-lactone structural feature and nonholostane type do not have a γ(18,20)-lactone but have
other structural features like holostane type glycosides.
4.1. Holostane Type Triterpene Glycosides
Depending on the position of double bond in the B and C ring of the aglycone (Figure 1),
holostane type glycosides can be further subdivided into three groups: glycosides with
3β-hydroxyholost-7(8)-ene, 3β-hydroxyholost-9(11)-ene, and 3β-hydroxyholost-8(9)-ene aglycone
skeletons. There are eight pentacyclic triterpene and 30 alkane side chain aglycone architectures
commonly found in holostane type glycosides (Figure 4). In these architectures, certain functional
groups are generally attached to the specific carbons: keto and β-acetoxy groups at C-16, and
α-hydroxy group at C-12 and C-17.
(a)
O
HO
MeO OH
O
HO
OH
HO
OH
HO
D-glucose
HO
OH
3-O-methyl-D-glucose
O
HO
HO OH
OH
D-xylose
O
HO
MeO OH
OH
3-O-methyl-D-xylose
O
HO
HO OH
OH
D-quinovose
O
O
HO O
O
HO
OH
HO
O
HO
MeO OH
HO
O
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
O
HO O
O
HO
OH
HO
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
HO
O
HO
HO O
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
HO
HO O
O
O
HO
O
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
O
HO O
O
HO
OH
HO
O
HO
HO OH
O
HO
O
HO
HO O
O
HO
HO OH
O
O
HO
HO OH
O
HO
HO O
OH
1
2
3
4
5
61
2
3
4
5
1
2
3
4
1
2
1
2
3
1
2
3
4
5
Xyl
Glc
MeGlc
Qui
Glc
MeGlc
O
O
O
O
O
O
O
OAc
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
HO HO
OH
1
46
8
9
10
11 13
30 31
32
3
16
17
20
21
18
HO
OH
O
HO
III III IV
VVI VII VIII
Sugar Sugar Sugar Sugar
Sugar Sugar Sugar Sugar
OH
OAc
Figure 3. Some common carbohydrate architectures found in sea cucumber glycosides.
Triterpene glycosides can be classified as holostane type having 3
β
-hydroxy-5
α
-lanostano-
γ
(18,20)-lactone structural feature and nonholostane type do not have a
γ
(18,20)-lactone but have other
structural features like holostane type glycosides.
4.1. Holostane Type Triterpene Glycosides
Depending on the position of double bond in the B and C ring of the aglycone (Figure 1),
holostane type glycosides can be further subdivided into three groups: glycosides with
3
β
-hydroxyholost-7(8)-ene, 3
β
-hydroxyholost-9(11)-ene, and 3
β
-hydroxyholost-8(9)-ene aglycone
skeletons. There are eight pentacyclic triterpene and 30 alkane side chain aglycone architectures
commonly found in holostane type glycosides (Figure 4). In these architectures, certain functional
groups are generally attached to the specific carbons: keto and
β
-acetoxy groups at C-16, and
α
-hydroxy
group at C-12 and C-17.
Mar. Drugs 2017, 15, 317 4 of 35
Figure 2. Common sugar units present in sea cucumber glycosides.
Figure 3. Some common carbohydrate architectures found in sea cucumber glycosides.
Triterpene glycosides can be classified as holostane type having 3β-hydroxy-5α-lanostano-
γ(18,20)-lactone structural feature and nonholostane type do not have a γ(18,20)-lactone but have
other structural features like holostane type glycosides.
4.1. Holostane Type Triterpene Glycosides
Depending on the position of double bond in the B and C ring of the aglycone (Figure 1),
holostane type glycosides can be further subdivided into three groups: glycosides with
3β-hydroxyholost-7(8)-ene, 3β-hydroxyholost-9(11)-ene, and 3β-hydroxyholost-8(9)-ene aglycone
skeletons. There are eight pentacyclic triterpene and 30 alkane side chain aglycone architectures
commonly found in holostane type glycosides (Figure 4). In these architectures, certain functional
groups are generally attached to the specific carbons: keto and β-acetoxy groups at C-16, and
α-hydroxy group at C-12 and C-17.
(a)
O
HO
MeO OH
O
HO
OH
HO
OH
HO
D-glucose
HO
OH
3-O-methyl-D-glucose
O
HO
HO OH
OH
D-xylose
O
HO
MeO OH
OH
3-O-methyl-D-xylose
O
HO
HO OH
OH
D-quinovose
O
O
HO O
O
HO
OH
HO
O
HO
MeO OH
HO
O
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
O
HO O
O
HO
OH
HO
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
HO
O
HO
HO O
O
O
HO OH
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
HO
HO O
O
O
HO
O
O
HO
OH
O
HO
MeO OH
HO
O
O
HO
O
O
HO O
O
HO
OH
HO
O
HO
HO OH
O
HO
O
HO
HO O
O
HO
HO OH
O
O
HO
HO OH
O
HO
HO O
OH
1
2
3
4
5
61
2
3
4
5
1
2
3
4
1
2
1
2
3
1
2
3
4
5
Xyl
Glc
MeGlc
Qui
Glc
MeGlc
O
O
O
O
O
O
O
OAc
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
HO HO
OH
1
46
8
9
10
11 13
30 31
32
3
16
17
20
21
18
HO
OH