Employing BINOL-Phosphoroselenoyl Chloride for Selective Inositol Phosphorylation and Synthesis of Glycosyl Inositol Phospholipid from Entamoeba histolytica

Article abstract of DOI:10.1002/chem.201701298

The chemical synthesis of glycosyl inositol phospholipids from Entamoeba histolytica is reported. The key feature of this synthesis is a regioselective phosphorylation reaction that occurs through desymmetrization of a myo-inositol derivative with phosphoroselenoyl chloride. A new protecting-group strategy was developed that utilizes allyl and alloc groups to synthesize complex glycolipids bearing unsaturated lipids. These developments provided an efficient synthetic route for various complex inositol phospholipids and their analogues. Furthermore, the binding affinity of the synthetic inositol phospholipids with mouse CD1d molecules has been evaluated, as well as the immunostimulatory activity.

Full text of DOI:10.1002/chem.201701298

A Journal of
Accepted Article
Title: Employing BINOL-phosphoroselenoyl chloride for selective
inositol phosphorylation and chemical synthesis of glycosyl
inositol phospholipid from Entamoeba histolytica
Authors: Toshihiko Aiba, Sae Suehara, Siew-Ling Choy, Yuuki
Maekawa, Hannelore Lotter, Toshiaki Murai, Shinsuke Inuki,
Koichi Fukase, and Yukari Fujimoto
This manuscript has been accepted after peer review and appears as an
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the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201701298
Link to VoR: http://dx.doi.org/10.1002/chem.201701298
Supported by

10.1002/chem.201701298
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Employing BINOL-phosphoroselenoyl chloride for selective
inositol phosphorylation and chemical synthesis of glycosyl
inositol phospholipid from Entamoeba histolytica
Toshihiko Aiba,[a],[b] Sae Suehara,[a] Siew-Ling Choy,[c] Yuuki Maekawa,[d] Hannelore Lotter,[c] Toshiaki
Murai,[d] Shinsuke Inuki,[a] Koichi Fukase,[b] and Yukari Fujimoto*[a]
Abstract: Here we describe the chemical synthesis of glycosyl
inositol phospholipids from Entamoeba histolytica. The key feature of
this synthesis is a regioselective phosphorylation reaction that
development in a mouse model through the host’s immune
responses.[7] EhLPPG has unique GPI-like structure:
Gal1Man2GlcN-myo-inositol-PO3-lipid,[8] which contains the
inositol phospholipids; EhPIa and EhPIb.[7]
occurs via desymmetrization of
a myo-inositol derivative with
phosphoroselenoyl chloride. We also developed a new protecting
group strategy that utilizes allyl and alloc groups to synthesize
complex glycolipids bearing unsaturated lipids. These developments
provided an efficient synthetic route for various complex inositol
phospholipids and their analogues. Furthermore, we have evaluated
the binding affinities of the synthetic inositol phospholipids against
mouse CD1d molecule and the immunostimuratory activities.
These structures have
a
characteristic long-chain
unsaturated fatty acid moiety either 28 or 30 carbon atoms in
length. An additional fatty acid exists at the 2-position of myo-
inositol in EhPIb (Figure 1). The configuration of the sn-2
position of the glycerol moiety and the galactose-linked site were
not clearly determined by spectroscopic data and were inferred
based on the previously reported configurations and
glycosylation site on similar types of protozoan GPI anchor, as
the sn-1 position of the glycerol connected to a long fatty acid
chain as a 2R configuration[7] and α-1,2 glycosidic linkage
between the terminal glycan and mannose. The diacylated
inositol phospholipid structure, EhPIb, showed similar
immunostimulatory activity to EhLPPG.[7] Although the isolated
EhLPPG and EhPI have been demonstrated to have intriguing
biological activities including immunomodulation via CD1d
binding, the effects of unique lipids and glycan structures on
their biological activities remain unclear due to the heterogeneity
of isolated compounds.
Introduction
Glycosylphosphatidylinositols (GPIs) are
a
class of
complex glycolipids that are widely expressed in eukaryotes.[1] In
protozoa, these glycoconjugates are major components of the
cell surface that were originally identified as virulence factors.[2]
They also have critical functions in host cell invasion[3] and in
evading innate immune responses[4] during infection. Owing to
their biological importance, particularly in the development of
diagnostic agents or vaccines, several total syntheses of
protozoan GPIs have been described.[5]
m
HO
HO
R1 = H
OR
O
m = 0, n = 0 :EhPIa
R1 = –COC15H31
Entamoeba histolytica, an intestinal protozoan parasite,
causes severe amoebiasis such as amoebic liver abscess (ALA)
and accounts for 100,000 deaths worldwide annually[6]. It has
HO
m = 1, n = 1: GIPL
m = 0, n = 0: EhPIb
O
HO
HO
HO
Acyl = R2 1a: 2S, 1b: 2R
m = 0, n = 1: GlcN-EhPIb
Acyl = R2 2a: 2S, 2b: 2R
Acyl = R2 3a: 2S, 3b: 2R
Acyl = R3 4a: 2S, 4b: 2R
Acyl = R45a: 2S, 5b: 2R
O
OH
O
recently
lipopeptidophosphoglycan (EhLPPG), which is
component of the cell membrane, plays an important role in ALA
been
reported
that
E.
histolytica
O
HO
HO
n
a
major
OH
O
O
O
R2
R3
=
=
HO
OR1
19
19
7
7
H3N
O
HO
O
O
OH
OH
O
Acyl
O
1
O
P
[a]
[b]
T. Aiba, S. Suehara, Dr. S. Inuki, Prof. Dr. Y. Fujimoto
Department of Chemistry, Faculty of Science and Technology
Keio University
3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan
E-mail: Fujimotoy@chem.keio.ac.jp
2
3
OH
OAcyl
R4
=
O
24
T. Aiba, Prof. Dr. K. Fukase
Figure 1. Proposed structure of glycosyl inositol phospholipid and inositol
phospholipid from Entamoeba histolytica.
Department of Chemistry, Graduate school of Science
Osaka University
1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan
S.-L. Choy, Dr. H. Lotter
Bernhard Nocht Institute for Tropical Medicine
Bernhard-Nocht- Str.74, Hamburg, 20359, Germany
Y. Maekawa, Prof. Dr. T. Murai
[c]
[d]
Department of Chemistry and Biomolecular Science, Faculty of
Engineering, Gifu University
1-1 Yanagido, Gifu, 501-1193, Japan
Supporting information for this article is given via a link at the end of
the document.
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Scheme 1. Retrosynthesis of glycosylinositolphospholipids 1a, 1b. Lev = levulinoyl, Alloc = allyloxycarbonyl, Bn = benzyl, Ph =
phenyl, Nap = naphthylmethyl, MOM = methoxymethyl,
Several synthetic studies of GPIs in recent years have
focused on synthesizing GPIs that bear unsaturated lipids. This
outcome is incompatible with the conventional protecting group
strategy using benzyl group.[9] In 2006, Nikolaev’s group
demonstrated a strategy utilizing benzoyl ester for permanent
protection of hydroxyl groups for the synthesis of GPI from T.
cruzi containing unsaturated lipids.[10] More recently, strategies
that employ an acid-labile protecting group such as para-
methoxybenzyl (PMB)[11] and 2-naphthylmethyl (Nap)[12] have
been developed. While these strategies have enabled the
syntheses of various functionalized GPIs, there are some
limitations to their use due to the undesired saponification of
fatty acid ester under basic conditions and the undesirable need
for the removal of acid-labile protecting groups under acidic
Here, we report an efficient strategy for synthesizing
glycosyl inositol phospholipids from E. histolytica bearing
unsaturated lipids. For the structure-activity relationship (SAR)
study of the sn-2 position of glycerol and glycan structures, we
aimed to synthesize the tetrasaccharide derivatives (GIPL) of
both stereoisomers of glycerol (1a and 1b) and monosaccharide
derivatives (GlcN-EhPIb) (2a and 2b). The key features of our
strategy include the use of allyl and allyloxycarbonyl (alloc)
groups to protect hydroxy groups permanently, and the
regioselective phosphorylation of myo-inositol using BINOL-
derived phosphoryl chlorides, such as phosphoroselenoyl
chloride, to ensure greater reactivity and selectivity. Furthermore,
we evaluated the binding affinity between synthesized
compounds and mouse CD1d (mCD1d) molecule and also their
immunostimulatory activities.
conditions.[11b] Thus, we planned
a new protecting group
strategy to enable the removal of the protecting group under
neutral conditions at the final stage.
The site-selective introduction of a phosphate to myo-
inositol was required to synthesize inositol lipids. Typical
methods for preparing chiral inositol building blocks are chiral
resolution[13] and chiral pool synthesis.[14] Recently, several
approaches for generating chiral inositol phosphate directly from
meso-inositol have also been reported. Miller and co-workers
Results and Discussion
The retrosynthetic analysis of 1a and 1b is shown in
Scheme 1. Considering the unique acyl modification at the myo-
inositol, unsaturated lipid structures at the acylglycerol, and also
the effect for the selective phosphorylation, we designed the
protecting group strategy. We planned to use allyl and alloc
groups for permanent protection of hydroxyl groups. In the final
step, these protecting groups were removed by a transition-
metal-catalyzed deallylation reaction. The compounds 7a and 7b
were delivered from α-selective glycosylation using azido-
glucose donor 8 and
inositol 9 and subsequent coupling with acylglycerols 10a and
10b bearing long-chain unsaturated lipids, which were prepared
by a Ni-catalyzed alkyl-alkyl cross coupling reaction.[18] The
phosphate group of inositol 9 was introduced during an early-
stage in this synthesis through regioselective phosphorylation
with BINOL-derived phosphoryl chlorides having O, S or Se.
We initially investigated the regioselective introduction of
phosphate group to meso-inositol 13,[17] by using chiral
phosphatizing reagents 14a, 14b or 14c (Table 1). In the case of
reported
desymmetrization of a meso-inositol derivative using peptide
catalysts,[15] and Jessen and co-workers reported
diastereoselective phosphorylation using chiral
an
enantioselective
phosphorylation
via
a
a
phosphoramidite reagent.[16] We have demonstrated a more
effective diastereoselective phosphorylation with utilizing BINOL
derived phosphoramidite reagent.[17] The method enabled us to
obtain the desired isomer with relatively higher selectivity and
was also advantageous for separating diastereomers. On the
other hand, our previous method using BINOL-phosphoramidite
required an excess of the phosphatizing reagent due to the
lower reactivity of BINOL-phosphoramidite compared with
BINOL-phosphorochloridate. Therefore, in this study, we aimed
to develop an efficient diastereoselective phosphorylation of
meso-inositol based on our previous results.
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phosphoryl chloride 14a (X = O), as we have previously
observed,[17] we did not achieve regioselectivity under the
present conditions either (entry 1 and 2). Specifically, the
reaction of 13 with (R)-BINOL-derived phosphoryl chloride (14a)
gave the desired product 11 at very low yield and with no
The inositol building block 9 for the synthesis of inositol
phospholipids 1a and 1b was prepared from compound 11
(Scheme 2). O-Allyl protection of 11 with allyl alcohol and
catalytic [CpRu(C3H5)(C9H6NCO2)]PF6 in 1,2-dichloroethane[20]
gave the desired compound 15 in 55% yield. Selective cleavage
of 4-O-PMB in 15 with DDQ generated the corresponding
alcohol in 57% yield (71% brsm). The sterically hindered
environment of 6-O-PMB by BINOL presumably caused this
regioselectivity. Transesterification to allyl ester gave the inositol
16. After protecting group manipulations and introduction of a
palmitoyl group, we obtained the desired inositol acceptor 9.
With the inositol building block 9 in hand, we advanced the
synthesis of inositol phospholipids 1a, 1b, 2a and 2b (Scheme
7). Glycosylation between 9 and azido-glucose donor 8 using
TMSOTf in Et2O/CH2Cl2 provided 19 in 81% yield (α/β = 4:1).
The pseudodisaccharides 7a and 7b were obtained by
Mitsunobu coupling[21] of mono-acylglycerol 10a or 10b and
removal of the Nap group. The deallylation reaction with
Pd(PPh3)4 in a high polarity solvent[22] proceeded smoothly and
was followed by reduction of the azide group with Zn-Cu.
selectivity (11:12
= 50:50, entry 1). Although using two
equivalents of 14a increased the yield, the regioselectivity was
not improved (entry 2). We next examined phosphatizing
reagents having sulfur or selenium atoms on phosphorus (14b
(X = S), 14c (X = Se)). These reagents have been developed as
chiral derivatizing agents for racemic alcohols and amines.[19]
Either the sulfur or selenium atom of these reagents can be
easily converted to oxygen by the subsequent addition of an
oxidant such as mCPBA. The use of phosphorothioyl chloride
14b provided the desired product but at a very low yield.
However, the selectivity was slightly increased (11:12 = 67:33)
(entry 3). Changing the reagent to phosphoroselenoyl chloride
14c improved the yield to 79% with good regioselectivity (11:12
= 86:14) (entry 4). These results indicate that as atomic radius
increases (O<S<Se), diastereoselectivity improves. Conducting
the reaction on a larger scale (ca. 10 g) also gave a similar yield
of the desired product with similar selectivity (74%, 11:12 =
88:12) (entry 5). Switching the reaction solvent from CH2Cl2 to
either THF or toluene decreased both the yield and selectivity
(entry 6, 7). The diastereomixture of 11 and 12 was separated
by the reported procedure to isolate the desired isomer 11. This
method using the phosphoroselenoyl chloride will be also
applicable for the various types of substrates.
Subsequent purification with
a Sephadex LH-20 column
produced GlcN-EhPIb 2a and 2b at 75% and 66% for the two
steps, respectively. The glycosylation of trisaccharide 6 (see
Supporting Information) and inositol 7a and 7b followed by
cleavage of the Lev group generated 20a and 20b. Finally,
global deprotection in a similar manner led to 1a and 1b (58%
for 1a, 60% for 1b in two steps). Structures of the target
compounds were characterized with 1H, 13C, 31P and 2D
NMRspectroscopy and ESI-Q-TOF mass spectrometry.
X
O
P
Cl
O
O
P
O
O
OMOM
OMOM
HO
O
HO
OH
X = O (14a), S (14b)
= Se (14c)
3
1
3
1
PMBO
OPMB
PMBO
OPMB
DMAP (2.0 equiv.)
O
P
O
P
OH
11 (12:3-P)
OH
13
O
O
O
O
OMOM
O
0 ºC, over night
then mCPBA
OMOM
O
AllylO
HO
a
Table 1. Regioselective phosphorylation of 13
PMBO
OPMB
PMBO
OPMB
OAllyl
OH
Entry
1 [c]
2 [c]
3
X (equiv.)
O (1.0)
Solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
Yield (%)[a]
d.r. (11:12) [b]
50:50
11
15
O
P
O
P
2
OAllyl
OAllyl
OAllyl
OAllyl
OMOM
O
OMOM
O
AllylO
AllylO
AllocO
O (2.0)
56
4 [d]
79
74
16
3
50:50
b, c
d, e, f
S (2.0)
67:33
HO
OPMB
OLev
OAllyl
OAllyl
4 [e]
5 [f]
6
Se (2.0)
Se (2.0)
Se (2.0)
Se (2.0)
86:14
16
17
O
O
88:12
O
C15H31
O
C15H31
OAlloc
OAllyl
AllylO
AllylO
76:24
i
g, h
OAlloc
OAllyl
LevO
O
HO
O
O
O
7
Toluene
61:39
P
P
OAllyl
OAllyl
AllylO
AllylO
[a] Isolated yield. [b] Determined by 1H NMR analysis. [c] Without mCPBA. [d]
Yield was determined by 1H NMR analysis. [e] 0.21 mmol of 14c was used. [f]
18
9
20 mmol of 14c was used. d.r.
dimethylaminopyridine, mCPBA = meta-chloroperoxybenzoic acid
= diastereomeric ratio, DMAP = 4-
Scheme 2. Synthesis of inositol building block 9. Reagents and conditions: a)
[CpRu(C3H5)(C9H6NCO2)]PF6, allyl alcohol, 1,2-dichloroethane, reflux, 55%; b)
DDQ, CH2Cl2/pH 7 phosphate buffer, 0 ºC, 57% (71% brsm); c) allyl alcohol,
NaH, THF, 60%; d) AllocOBt, DMAP, CH2Cl2, 97%; e) DDQ, CH2Cl2/pH 7
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phosphate buffer, 96%; f) levulinic acid, EDCI•HCl, DMAP, CH2Cl2, 80%; g)
50% TFA in CH2Cl2, 0 ºC; h) palmitic acid, DCC, DMAP, CH2Cl2, 76% for two
steps; i) H2NNH2·AcOH, CH2Cl2/MeOH, 97%. THF = tetrahydrofuran, DDQ =
activate NKT cells by the presence of CD1d and simultaneously
TLR receptor signaling.[7] The synthesized fragment structures of
EhLPPG will lead to further investigations of the
immunomodulatory mechanism of the EhLPPG.
2,3-dichloro-5,6-dicyano-p-benzoquinone, Bt
=
benzotriazole, TFA
=
trifluoracetic acid, EDCI = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.
OAllyl
O
OAllyl
O
O
HO
AllylO
O
NapO
AllylO
O
C15H31
N3
AllylO
O
C15H31
8
+
9
a
N3
b, c, d
e, f
OAlloc
OAllyl
AllylO
O
2a, 2b
O
OAlloc
OAllyl
O
O
O
1
O
P
O
OAllyl
P
2
3
OAllyl
AllylO
O
AllylO
19
7
19
7a: 2S, 7b: 2R
O
AllocO
AllylO
OH
O
AllylO
O
AllocO
AllocO
AllylO
O
OAlloc
O
O
AllocO
AllylO
6
+
i, j
g, h
1a, 1b
OAlloc
O
O
7a or 7b
O
AllocO
O
C15H31
N
3 AllylO
OAlloc
OAllyl
O
O
O
1
O
P
2
3
OAllyl
AllylO
O
19
7
20a: 2S, 20b: 2R
O
Scheme 3. Synthesis of GlcN-EhPIb 2a, 2b and GIPL 1a, 1b. Reagents and
conditions: a) TMSOTf, MS4A, CH2Cl2/Et2O, –20 ºC to rt, 81% (a/b = 4/1); b)
LiBr, acetone, reflux; c) 10a (for 7a) or 10b (for 7b), DEAD, PPh3, THF; d)
DDQ, CH2Cl2/pH 7 phosphate buffer, 7a: 27%, 7b: 32% for three steps; e)
Pd(PPh3)4, 1,3-DMBA, CH2Cl2/MeOH/H2O, 40 ºC; f) Zn-Cu, AcOH,
THF/MeOH/H2O, 2a: 75%, 2b: 66% for two steps; g) TMSOTf, MS4Å,
CH2Cl2/Et2O, –20 ºC to rt; h) H2NNH2·AcOH, CH2Cl2/MeOH, 20a: 38%, 20b:
22% for two steps; i) Pd(PPh3)4, 1,3-DMBA, CH2Cl2/MeOH/H2O, 40 ºC; j) Zn-
Cu, AcOH, THF/MeOH/H2O, 1a: 60%, 1b: 58% for 2 steps. DEAD = diethyl
azodicarboxylate, 1,3-DMBA = 1, 3-dimethylbarbituric acid.
Figure 2. A) The binding affinity of synthesized compounds 1b, 2b and α-
GalCer against mCD1d with the competitive ELISA. The assays were done in
duplicate and the error bars indicate Standard Deviation (SD). B) Induction of
IFN-γ in murine spleen cells by synthetic inositol phospholipids 1b and 2b in
comparison with the isolated EhLPPG. The assays were done in duplicate and
the error bars indicate Standard Deviation (SD).
We next investigated the binding affinity between mCD1d
and the synthesized glycosyl inositol phospholipids possessing
R-configuration at glycerol, tetrasaccharide 1b and GlcN-EhPIb
2b, by competitive binding ELISA based on reported protocols[23]
We used protein G coated plate for capturing mCD1d-Fc fusion
protein and 18:1 biotinylated phosphatidylethanolamine (PE) as
an indicator, which was shown to bind mCD1d molecule (IC50
value of non-labeled PE: 1.33 µM.[23]) In this competition assay,
1b and 2b indicated direct binding to mCD1d and showed lower
affinity than the known CD1d ligand, α-galactosylceramide (α-
GalCer; 0.257 µM), and 2b (1.62 µM) displayed slightly lower
IC50 value than 1b (3.89 µM). The data demonstrated that this
type of inositol phospholipids directly bind to mCD1d, for the first
time. We also analyzed the immunostimulatory activities of the
synthesized glycosyl inositol phospholipids compared to the
isolated natural EhLPPG. The cytokine induction of mouse
spleen cells was analyzed by enzyme-linked immunosorbent
assay (ELISA) (Figure 2B). The GlcN-EhPIb 2b showed higher
IFN-γ inducing activities than tetrasaccharide 1b and EhLPPG in
the cytokine induction assay. The EhLPPG has been shown to
.
Conclusions
In conclusion, we have developed
a regioselective
phosphorylation of myo-inositol using phosphoroselenoyl
chloride, and successfully implemented the protecting group
strategy utilizing allyl/alloc groups for permanent protection of
hydroxyl groups. Using these methods, we successfully
accomplished the chemical synthesis of glycosyl inositol
phospholipids 1a, 1b, 2a, and 2b from E. histolytica. The
synthetic method we presented in this report has the potential
for synthesizing various inositol phospholipids bearing reduction-
sensitive, acid or base-labile functionalities. We evaluated the
binding affinity of the synthesized 1b and 2b against mCD1d,
and obtained the direct binding against mCD1d. We also
analyzed the immunostimulatory activities of synthesized
compounds, revealing that 2b induced higher levels of IFN-γ
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10.1002/chem.201701298
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secretion than EhLPPG. The further investigation of their
biological activities including 1a and 2a is now underway.
Yamaguchi, Dr. S. Yanaka and Dr. N. Inazumi for NMR
spectroscopy experiment.
Keywords: inositol phospholipid • phosphorylation • synthetic
strategy • Entamoeba histolytica • CD1d
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Pierce protein G coated 96 well plates (Thermo Fisher Scientific)
were washed with 200 µL of PBST (PBS containing 0.05%
Tween-20) three times. 50 µL of mouse CD1d:Ig fusion protein
(BD bioscience) (10 µg/mL in PBS) for 1h at room temperature.
25 µL of Serially diluted inositol phospholipids and
α-galactosylceramide (GalCer) with PBS were added to the
plates and then added 25 µL of 18:1 biotinyl PE (1,2-dioleoyl-sn-
[9]
Y. H. Tsai, X. Y. Liu, P. H. Seeberger, Angew. Chem. 2012, 124,
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[11]
glycero-3-phosphoethanolamine-N-(Biotinyl),
Avanti
Polar
Lipids) (8 µg/mL in PBS) and incubated for overnight at 37 ºC.
After washing the plates with PBST three times, mCD1d:Ig-
biotinyl PE complex was detected with HRP-labeled Avidin
(Biolegend). Inhibition curves were constructed using GraphPad
Prism software (ver. 7.02, GraphPad).
[12]
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B. Y. Lee, P. H. Seeberger, D. V. Silva, Chem. Commun. 2016, 52,
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[14]
[15]
Mouse spleen cell stimulation assay
Spleen cells were isolated from C57BL/6 mice, seeded at a
concentration of 2x105/well and incubated with isolated EhLPPG
or synthetic inositol phospholipids at indicated concentrations for
48 h. IFN-γ induction in the supernatant was determined by
ELISA.
[16]
[17]
[18]
Acknowledgements
[19]
This work was supported in part by Grants-in-Aid for Scientific
Research (Nos. JP26282211, JP26102732, JP16H01162 and
JP16H01139) from the Japan Society for the Promotion of
Science, by ERATO Murata Lipid Active Structure Project, by a
funding program for Next Generation World Leading
Researchers (NEXT Program; LR025) from JSPS and CSTP, by
Yamada Science Foundation, and by The Sumitomo Foundation,
by Mizutani Foundation for Glycoscience, by Nagase Science
Technology Foundation. We thank Prof. K. Kato, Dr. T.
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This article is protected by copyright. All rights reserved.

10.1002/chem.201701298
Chemistry - A European Journal
FULL PAPER
FULL PAPER
Toshihiko Aiba, Sae Suehara, Hannah
Bernin, Yuuki Maekawa, Hannelore
Lotter, Toshiaki Murai, Shinsuke Inuki
Koichi Fukase, Yukari Fujimoto*
Page No. – Page No.
Employing BINOL-phosphoroselenoyl
chloride for selective inositol
phosphorylation and chemical synthesis
of glycosylinositolphospholipid from
Entamoeba histolytica
Text for Table of Contents
This article is protected by copyright. All rights reserved.