A Concise Synthesis of Oligosaccharides Derived From Lipoarabinomannan (LAM) with Glycosyl Donors Having a Nonparticipating Group at C2

Article abstract of DOI:10.1002/ejoc.201901915

Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death over the world, and lipoarabinomannan (LAM) has been confirmed to play significant roles in this process. In this study, a convenient synthetic approach ha

Full text of DOI:10.1002/ejoc.201901915

DOI: 10.1002/ejoc.201901915
Full Paper
Glycoconjugates
A Concise Synthesis of Oligosaccharides Derived From
Lipoarabinomannan (LAM) with Glycosyl Donors Having a
Nonparticipating Group at C2
Zhihao Li,[a] Changping Zheng,[a] Marco Terreni,[b] Teodora Bavaro,[b] Matthieu Sollogoub,[a]
and Yongmin Zhang*[a]
Abstract: Mycobacteria infection resulting in tuberculosis (TB) It's noteworthy that enzymatic hydrolysis was applied to pre-
is one of the top ten leading causes of death over the world,
and lipoarabinomannan (LAM) has been confirmed to play sig-
nificant roles in this process. In this study, a convenient syn-
thetic approach has been developed for the synthesis of oligo-
saccharides derived from LAM starting with commercially avail-
able substrates and reagents. The key steps for stereoselective
construction of glycosidic bonds by acceptors glycosylated with
donors without neighboring participating group were achieved.
pare mannose building blocks and one step of birch reaction
was used to deprotect acetyl and benzyl groups as well as re-
duce the azide group, which can avoid multiple chemical proce-
dures. Finally, five oligosaccharides with terminal amino group
at the anomeric substituent were furnished which could be
used for conjugation with proteins as potential vaccines against
TB.
Introduction
an α-1,6-and α-1,2-linked mannan backbone, in which it con-
tains an arabinan domain containing an α-1,5-linked D-arabino-
furanosyl chain.[2a,5]
As one of the top 10 causes of death worldwide in 2018, tuber-
culosis (TB) killed 1.5 million individuals including 251 000 HIV
affected cases. Although great effort has been made that 7 mil-
lion people have received record levels of lifesaving TB treat-
ment, lots of individuals still missed out.[1] Since the efficacy of
drugs is limited by multiple drug resistance (MDR) and exten-
sively-drug resistance (XDR), patients need to take a combina-
tion of three specific drugs to avoid the problem which is time
and money consuming.[2] So vaccine is still an ideal therapy
fighting against TB. However, the only licensed vaccine BCG
(Bacillus Calmette-Guérin) existing for 99 years is not effective
enough, especially for the teenagers and adults.[3] It is essential
to develop novel vaccines for TB prevention and immunother-
apy.
Carbohydrates are one kind of complicated and diverse class
of biomolecules commonly found in nature playing important
roles in a multitude of biological processes and a series of phar-
maceuticals and vaccines are based on carbohydrates.[4] As the
major component in the cell wall of mycobacterium, lipoarabi-
nomannan (LAM), a polysaccharide, has been attracting re-
searchers′ interests. Its structure is well-established containing
Due to the significant role of LAM in mycobacterium infec-
tion, nowadays researchers have paid much attention to LAM-
based vaccines and got some positive results.[6] However, it is
extremely difficult to synthesize the LAM using the current
technology due to its complicated structure, therefore studying
its simplified analogues or derivatives is becoming a matter of
research. Recently, a series of works on LAM mimetic synthesis
have been reported. Bundle et al. succeeded in synthesizing
three oligosaccharides, after conjugating them to the polymers,
the conjugates displayed great characteristics for assay of anti-
body.[7] Guo et al. prepared several oligosaccharides as candi-
dates for protein conjugation with decent biological activity
and they concluded that the oligosaccharide part is important
for the activity.[8] Wattanasiri et al. synthesized LAM mimetic
polysaccharide using rapid synthetic approach and evaluated
its immunological properties with positive results.[9] Bavaro et
al. used monosaccharide, disaccharide and trisaccharide to con-
jugate the TB protein and all the three glycoproteins showed
certain activity.[10] Besides, several linkers have been reported
to conjugate sugar with protein, polypeptide or other func-
tional substances[2b,11] which is also helpful for LAM-based re-
search development. The glycoprotein as vaccine candidates
has received considerable critical attention in this field.
[a] Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR
8232,
4 Place Jussieu, 75005 Paris, France
E-mail: yongmin.zhang@upmc.fr
Although LAM has been proved to play important roles in
the process of Mycobacterium tuberculosis (M.TB) infection,
there is no obvious evidence to show which part is the core
unit for the immunological activity. Since little work has been
devoted to looking for the key section, the oligosaccharide fun-
http://www.ipcm.fr/ZHANG-Yongmin?lang=fr
[b] University of Pavia, Drug Sciences Department,
Viale Taramelli 12, 27100 Pavia, Italy
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201901915.
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damental study is crucial for the LAM-based vaccine. Besides,
In this study, we describe our efforts for the synthesis of a
during the LAM synthesis study, highly stereoselective construc- variety of oligosaccharides derived from LAM. The key steps for
tion of glycosidic bond has always been regarded as a chal- stereoselective construction of glycosidic bonds by acceptors
lenge.
glycosylated with donors without neighboring participant were
Figure 1. Five synthesized oligosaccharides.
Figure 2. Comparison of retrosynthetic analysis for synthesizing trisaccharide 30 and tetrasaccharide 32.
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achieved. In addition, enzymatic hydrolysis was used to prepare charide acceptor J will be conducted, and if “2+2” strategy, the
the mannose building blocks, and one step of birch reaction glycosylation between disaccharide donor g with no neighbor-
was used to deprotect acetyl and benzyl groups as well as re- ing participant and disaccharide acceptor h will be conducted.
duce the azide group, avoiding redundant procedures. Finally, For both strategies, avoiding isomer is still an issue during the
five oligosaccharides with terminal amino group at the ano- glycosylation.
meric substituent derived from LAM were successfully synthe-
sized, as shown in Figure 1, which can be used to conjugate
with protein as potential TB vaccines.
Taken “Top to Bottom” and “3+1” strategies, based on the
retrosynthetic analysis, intermediates needed are shown in Fig-
ure 3 for synthesis of five protected oligosaccharides. At first,
synthesis of compound 29 would start with disaccharide 26
and monosaccharide 9, while the disaccharide 26 is con-
structed by monosaccharide 3 and 23. Next, for compound 12,
except using monosaccharide 9, a different disaccharide 6
would be used which can be constructed by monosaccharide
3 and 5. Finally, for compound 21 and 22, applying “3+1” strat-
egy, trisaccharide 19, 20 and monosaccharide 9 are needed.
And the trisaccharide 19 or 20 can be formed by disaccharide
6 and monosaccharide 18 with two different configurations. As
for 15′, trisaccharide 15 made by compound 6 and 13 as well
as monosaccharide 9 need to be acquired as building blocks to
finish the construction.
Results and Discussion
Synthetic Strategy Analysis
In this work, for the oligosaccharide construction, we directly
adopted “Top to Bottom strategy”, and “Bottom to Top strat-
egy” was not tested. Taking targeting compound 30 in Fig-
ure 2A as an example, whether synthesizing from top to bottom
or from bottom to top, it seems that both strategies have no
significant difference. If using “Bottom to Top strategy”, all the
glycosylations will be carried out with donors having neighbor-
ing participant, which is helpful for stereoselectivity. However,
applying “Top to Bottom strategy”, the building block C can
be easily prepared by enzymatic hydrolysis, avoiding redundant
procedures. In addition, as another example of oligosaccharide
Synthesis of Oligosaccharides with Neighboring
Nonparticipating Arabinose Donor
32 shown in Figure 2B, “Top to Bottom with 3+1” strategy will As shown in Scheme 1, the synthesis started with commercially
be used. For “3+1” strategy, the glycosylation between disac- available -arabinose 1. Since in the acetylation process of
D
D-
charide donor I with no neighboring participant and monosac- arabinose, it may transfer from furanose form to pyranose form,
Figure 3. Retrosynthetic analysis for compound 12, 15′, 21, 22 and 29.
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Scheme 1. Reagents and conditions: Transformations (a–c) have been conducted using reported protocols;[8,13,14] (d) CH3OH, CH3ONa, RT, 2 h, 96 %; (e)
BF3·Et2O, 4Å MS, CH2Cl2, -50 °C, 30 min, 86 %.
in order to obtain the peracetylated arabinose with furanose reaction was carried out at 0 °C, almost 2/3 of product turned
form 2, hydroxy group at C-1 or C-5 position always needs to into 7 because the Lewis acid activated the STol group, and
be protected in advance. Although compound 2 was reported when the temperature reached –10 °C and –30 °C, the ratio
to be obtained directly by one step in the literature,[12] using dropped to 1/2 and 1/3, respectively. If temperature decreased
the same method, furanose and pyranose mixture was obtained to –50 °C or lower, no by-product 7 was found in 1H NMR spec-
which was confirmed by 13C NMR spectrum (see supporting trum since the sulfur group is not activated at low temperature.
information). So, in our hand, peracetylated arabinose 2 was
In Scheme 2, mono-deprotected compound 9 bearing a free
C-6 OH was prepared by enzymatic hydrolysis from known com-
pound 8 in high yield. In this step, the enzymatic hydrolysis
was used to prepare building block 9, which can avoid multiple
chemical procedures. The enzyme CRL can selectively remove
the acetyl group at C-6 position of monosaccharides. Further,
the glycosylation reaction was carried out between acceptor 9
and donor 6 to furnish the trisaccharide 12 by NIS/AgOTf as
promoters in CH2Cl2. Due to no neighboring group participa-
tion during the glycosylation, isomers of α and ꢀ (1:2) were
formed. On the other hand, the STol group in disaccharide 6
was removed using NIS, AgOTf and 2,4,6-Tri-tert-butylpyrimi-
dine (TTBP) in wet CH2Cl2 to get compound 10 with free
hydroxy at the anomeric center and then intermediate 10 was
transformed into trichloroacetimidate 11 at 0 °C with CCl3CN
synthesized by methyl glycoside intermediate, acetylation and
anomeric acetylation from D
-arabinose for three steps.[13] Then
compound 2 was used to prepare the intermediate 3 by selec-
tively anomeric acetyl deprotection and imidate introduc-
tion.[14] Meanwhile the known compound 4 was furnished by
anomeric introduction of bromide, ortho-ester formation, acetyl
deprotection, benzylation and anomeric p-methylphenyl thio-
glycoside (STol) introduction for five steps from the same start-
ing material 2 according to the literature.[8] Next, the acetyl
group at C-2 position in compound 4 was removed by Zemplén
transesterification (CH3ONa/CH3OH) to give the acceptor 5. At
last, a glycosylation between acceptor 5 and donor 3 was con-
ducted to furnish disaccharide 6 in the yield of 86 % at low
temperature catalyzed by BF3·Et2O.
In the process of forming disaccharide 6, we found that reac- and DBU. At last, the imidate 11 was used as donor to glycosyl-
tion temperature has an effect on the ratio of by-product 7, ate with acceptor 9 using BF3·Et2O catalyst in Et2O to obtain
and low temperature can avoid the by-product 7. When the the trisaccharide 12 with good α selectivity successfully. We
Scheme 2. Reagents and conditions: (a) immobilized CRL enzyme (1400 IU/g), acetonitrile, KH2PO4, pH = 4, RT, 24 h, 85 %; (b) NIS, AgOTf, 4Å MS, CH2Cl2,
–10 °C, 30 min, 30 %; (c) NIS, AgOTf, TTBP, wet CH2Cl2, 0 °C–RT, 1 h, 91 %; (d) CCl3CN, DBU, CH2Cl2, 0 °C, 30 min, 90 %; (e) BF3·Et2O, 4 Å MS, Et2O, –30 °C, 1 h,
12 (69 %), 15 (60 %), 16 (65 %), respectively; (f) NIS, TMSOTf, 4 Å MS, CH2Cl2, –10 °C, 1 h, 78 %.
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propose that Et2O firstly combined the anomeric carbon in do-
It's well known that donors with neighbouring group partici-
nor 11 leading to more ꢀ configuration product, and then the pation are always used for stereoselective construction of glyc-
acceptor 9 attacked the intermediate from back with Et2O leav-
ing, producing more α compound 12. Besides, the known com-
pound 13 and 14 were synthesized by the similar enzymatic
method with excellent yield[11b] and used as acceptor to furnish
15 and 16 in Et2O. Next, in order to get 15′ the glycosylation
was tried between trisaccharide 15 and monosaccharide 11 by
NIS and AgOTf. However, the formal promoter cannot remove
the sulfur group in 15′ because of pyranose′s poor activity as
well as the disarming of acetyl. Fortunately, changing catalyst
to NIS and TMSOTf can achieve the activation and 15′ was
formed with decent yield at low temperature.
In Scheme 3, compound 18 was synthesized from monosac-
charide 17, which was obtained by C-5 OH protection with TBS
group and then acetylation. By adding BF3·Et2O at 0 °C to intro-
duce the STol group at the anomeric center and deprotecting
the TBS group at C-5 position was achieved in one step to pre-
pare compound 18 with the yield of 66 %. With building blocks
11 and 18 in hand, the glycosylation was performed to furnish
trisaccharide 19 and 20 using Lewis acid as promoter. The dif-
ferent configurations were confirmed by the 13C NMR spec-
trum,[2b] and the coupling constant for 19 was 105 ppm and
for 20 was 101 ppm. In this step, it needs the careful chroma-
tography to separate them. Then catalyzed by NIS and AgOTf
at –10 °C, donors 19 and 20 were used directly to glycosylate
acceptor 9 to furnish compounds 21 and 22 in excellent yields,
respectively.
osidic bonds. In our work, the arabinose donor with neighbor-
ing nonparticipant was used for glycosylation, and glycosyl-
ations were studied and compared in Table 1. In entry 1, com-
pound 6 was used as donor to directly react with acceptor 11,
more ꢀ isomer was obtained distinguished from the 13C NMR
spectrum. Since DMF may affect the configuration in pyranose
donor according to the literature,[15] in the entry 2, DMF along
with NIS/AgOTf as promoters were used at low temperature.
However, it was seen that preactivating the donor with DMF
added can slightly affect the isomer ratio, and the yield de-
ceased obviously because the donor intermediate is activated
that by-product may appear before adding acceptor 9. Further
in the entry 3, Et2O was used for donor 6 and acceptor 9 glyc-
osylation with NIS/AgOTf as promoters. However, no reaction
was observed due to the poor solubility and catalytic ability of
promoters in Et2O. Next, the donor imidate 11 with BF3·Et2O as
catalyst in the Et2O solvent (entry 4) at –30 °C produced more
α than ꢀ isomer with the ratio of α and ꢀ 3:1. Then given the
results of entry 5 and 6, compared with entry 4, different
groups at C-1 position of the acceptors (13 and 14) did not
affect isomer ratio too much. When acceptor 18 was used as
donor to glycosylate 11 at the same temperature in Et2O, the
ratio changed in some degree, which indicated changing the
acceptor from pyranose to furanose may affect isomer ratio (en-
try 7).
Scheme 3. Reagents and conditions: (a) thiocresol, BF3·Et2O, CH2Cl2, 0 °C, 2 h, 66 %; (b) BF3·Et2O, 4Å MS, Et2O, 1 h, –30 °C, 19 (58 %), 20 (29 %); (c) NIS, AgOTf,
4Å MS, CH2Cl2, –10 °C, 30 min, 82 %; (d) NIS, AgOTf, 4Å MS, CH2Cl2, –10 °C, 30 min, 84 %.
Table 1. Arabinose donors without neighbouring group participation for glycosylation.
Entry
Donor
Acceptor
Solvent
Catalyst
Temperature
Targeted Product
Total Yield
(Ratio of α/ꢀ)
1
2
3
4
5
6
7
6
6
6
11
11
11
11
9
9
9
9
13
14
18
CH2Cl2
CH2Cl2
Et2O
Et2O
Et2O
NIS, AgOTf
NIS, AgOTf, DMF
NIS, AgOTf
BF3·Et2O
BF3·Et2O
BF3·Et2O
–10 °C
–30 °C
–10 °C
–30 °C
–30 °C
–30 °C
–30 °C
12
12
–
12
15
16
19
90 % (1:2)
40 % (1:1.8)
–
92 % (3:1)
80 % (3:1)
87 % (3:1)
88 % (2:1)
Et2O
Et2O
BF3·Et2O
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Scheme 4. Reagents and conditions: (a) BF3·Et2O, 4Å MS, CH2Cl2, –50 °C, 30 min, 90 %; (b) NIS, AgOTf, 4Å MS, CH2Cl2, –10 °C, 30 min, 53 %; (c) NIS, AgOTf,
TTBP, wet CH2Cl2, 0 °C-RT, 1 h, 85 %; (d) CCl3CN, DBU, CH2Cl2, 0 °C, 1 h, 90 %; (e) BF3·Et2O, 4Å MS, Et2O, –30 °C, 3 h, 75 %; (f) BF3·Et2O, 4Å MS, Et2O/CH2Cl2
(15:1), –30 °C, 3 h, 45 %.
Synthesis of Oligosaccharides with Neighboring
Nonparticipating Mannose Donor
construct trisaccharide 28 using BF3·Et2O at –30 °C in mixed
solution of Et2O and CH2Cl2 (15:1), because compound 27 is
not well soluble in Et2O. The pure α product was obtained with
decent yield.
In Scheme 4, the known compound 23 was synthesized by 6
steps according to the literature[16] and then it was taken as
acceptor to furnish disaccharide 24 with donor 3 at low temper-
ature using Lewis acid. Since STol is less reactive in mannose
than arabinose, no by-product was found when temperature
changed. Then compound 24 was used as donor directly to
glycosylate 9 by NIS/AgOTf at –10 °C to furnish trisaccharide
29, where isomer mixture was obtained (α/ꢀ = 2:1). On the
other hand, the STol group at C-1 position of 24 was removed
by NIS, AgOTf and TTBP in wet CH2Cl2 to obtain intermediate
25 which was transformed into imidate 26. Surprisingly, when
imidate 26 was used as donor to glycosylate acceptor 9 in Et2O
for furnishing 29, pure α isomer was formed at low temperature
with high yield.
In this study, mannose donor without neighboring partici-
pant for glycosylation was also studied and compared in
Table 2. Comparison of entry 1 and 2 indicated that using Et2O
as solvent can promote α isomer ratio without getting ꢀ isomer.
In entry 3, when acceptor 18 was used, no desired compound
was found. That is because the activity of furanose is generally
higher than that in pyranose during glycosylation, leading to
catalyst first activated the STol group in acceptor 18. In entry
4, with compound 27 as acceptor, pure α isomer 28 can be
obtained in Et2O and CH2Cl2 mixed solution (15:1). However,
when decreasing the ratio to 8:1 in entry 5, ꢀ isomer also ap-
peared, which demonstrated that Et2O taking the huge part in
mixed solvent that promotes α product forming.
In addition, building block 27[11b] that was prepared by en-
zyme catalyst was also glycosylated with intermediate 26 to
Table 2. Mannose donor without neighbouring group participation for glycosylation.
Entry
Donor
Acceptor
Solvent
Catalyst
Temperature
Targeted Product
Total Yield
(Ratio of α/ꢀ)
1
2
3
4
5
24
26
26
26
26
9
9
18
27
27
CH2Cl2
Et2O
Et2O
Et2O/CH2Cl2 (15:1)
Et2O/CH2Cl2 (8:1)
NIS, AgOTf
BF3·Et2O
BF3·Et2O
BF3·Et2O
BF3·Et2O
–10 °C
–30 °C
–30 °C
–30 °C
–30 °C
29
29
–
28
28
80 % (2:1)
75 % (1:0)
–
45 % (1:0)
50 % (3:1)
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Scheme 5. Reagents and conditions: (a) to (e) liquid NH3, Na, CH3OH, THF, –60 °C, 30 min, 30 (59 %), 31 (53 %), 32 (55 %), 33 (54 %) and 34 (55 %), respectively.
Deprotection and Reduction
which can avoid multiple chemical procedures. Finally, five
oligosaccharides with amino group at reducing end were fur-
nished which can be used for conjugation with TB protein as
potential vaccines.
These are just our preliminary results. Although conjugation
with proteins and investigations of the ability of glycoconju-
gates on the mycobacteria will be studied and reported in the
future, it is clear that this work can accelerate the study of LAM-
based vaccines and oligosaccharides related with human dis-
eases.
Finally, in Scheme 5, with two trisaccharides (12 and 29) and
three tetrasaccharides (15′, 21 and 22) in hand, one step full-
deprotection was performed to deprotect benzyl and acetyl
groups using sodium in liquid ammonia at –60 °C. Meanwhile,
azide group was reduced during the birch reaction. The yields
for the five reactions are all around 55 %. The five compounds
will be used to conjugate TB proteins and evaluated biological
activity in the future. Since it is reported that SCH2CN can also
be used for protein conjugation,[11b] we tried to deprotect the
benzyl groups in compound 28. However, no targeting com-
pound was detected by birch reaction, catalytic hydrogenation
and other methods. For birch reaction, SCH2CN group changed
to SH according to the mass spectrum, while catalytic hyd-
rogenation failed to remove the benzyl group because sulfur
poisoned the palladium promoter.
Experimental Section
General: All chemicals were purchased as reagent grade and used
without further purification. All reactions were carried out under Ar
atmosphere and anhydrous conditions with freshly distilled sol-
vents, unless otherwise noted. Reactions were monitored by thin-
layer chromatography (TLC) on a pre-coated plate of silica gel 60
F254 (Merck) and detection by charring with sulfuric acid. Solvents
were evaporated under reduced pressure and below 40 °C (water
bath). Column chromatography was performed on silica gel 60
(230–400 mesh, Merck). All the new compounds were fully charac-
Conclusion
In this study, a concise synthesis of five oligosaccharides de-
rived from LAM was achieved. The key steps for highly stereo-
selective construction of glycosidic bonds by acceptors glyco-
sylated with donors without neighbouring group participantion
were achieved, during which the effect of Et2O was significant.
Using the solvent effect of Et2O can provide products with high
α selectivity for arabinose donor 11 and pure α products for
mannose donor 25. It's noteworthy that enzymatic hydrolysis
was applied to prepare mannose building blocks and one step
1
1
terized by H and 13C NMR, as well as HRMS. H NMR and 13C NMR
spectra were recorded at 400 MHz and 100 MHz with Bruker
AVANCE DRX 400 spectrometer. The chemical shifts were referenced
to the solvent peak, 7.26 ppm (1H) and 77.16 ppm (13C) for CDCl3
at 25 °C, chemical shifts (δ) are given in parts per million downfield
from internal Me4Si or with DHO signal as a reference when D2O
was used as the solvent, and coupling constants were given in Hz.
Complete assignment of all NMR signals was performed using a
of birch reaction was used for deprotection and reduction, combination of 1H,1H-COSY and 1H,13C-HSQC experiments. High-
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resolution mass spectra (HRMS) were recorded with a Bruker Micro-
61.26, 48.13, 28.68, 20.87, 20.74, 20.70. HR ESI-TOF MS (m/z): calcd.
TOF spectrometer in electrospray ionization (ESI) mode, using for C30H46N6O18Na [2M + Na]+, 801.2761, found 801.2748.
Tuning-Mix as reference.
3-Azidopropyl (2,3,4-Tri-O-acetyl-α-D-arabinofuranosyl)-(1→2)-
4-Methylphenyl 3,5-Di-O-benzyl-1-thio-α-D-arabinofuranoside
(3,5-di-O-benzyl-α-D-arabino-furanosyl)-(1→6)-2,3,4-tri-O-
(5): To a solution of 4 (500 mg, 1.04 mmol) in CH2Cl2 (5 mL) was
acetyl-α-D-mannopyranoside (12): To a solution of 6 (600 mg,
added MeONa in MeOH (1
M) until the pH value reached 10. The
0.86 mmol) in 16 mL of wet CH2Cl2 (20 % H2O) was added NIS
(390 mg, 1.72 mmol), AgOTf (221 mg, 0.86 mmol) and TTBP
(640 mg, 2.58 mmol). The solution was stirred for 1 h until no 6
left. The crude was purified by column chromatography to give 10
(462 mg, 91 %) as colorless syrup. Rf = 0.5 (cyclohexane/ethyl acet-
ate = 1:1). All the 10 was immediately put into 6 mL of dry DCM
under argon and then CCl3CN (780 μL, 8.6 mmol) and DBU (130 μL,
0.86 mmol) were added to the solution at ice bath. The solution
was stirred for 1 h at 0 °C and solution was removed under vacuo
and purified by column chromatography with 1 % triethylamine
added cyclohexane/ethyl acetate (3:2). Rf = 0.5 (cyclohexane/ethyl
acetate = 3:2). 11 should be used without delay for its poor stability.
The dried 11 (50 mg, 0.068 mmol), 9 (43 mg, 0.11 mmol) and acti-
vated 4Å MS (100 mg) were mixed together in anhydrous Et2O
(1.5 mL). The mixture was stirred for 1 h at RT under argon. BF3·Et2O
(10 μL, 0.07 mmol) was added and the reaction was left for 1 h at
–30 °C before being quenched by triethylamine. The resulting crude
product was purified by column chromatography (DCM/ethyl acet-
ate = 8:1) getting 12 (45 mg, 69 %) as colorless syrup. Rf = 0.3
solution was stirred at RT for 2 h before TLC showing the disappear-
ance of 4. The mixture was neutralized with Amberlite IR 120 (H+),
filtered, and concentrated. Then the crude was purified by column
chromatography to give 5 (438 mg, 96 %) as colorless syrup. Rf =
0.35 (cyclohexane/ethyl acetate = 4:1). 1H NMR (400 MHz, CDCl3)
δ = 7.44 (d, J = 7.8 Hz, 2H, Ph), 7.39–7.28 (m, 10H, Ph), 7.14 (d, J =
7.8 Hz, 2H, Ph), 5.50 (s(br.), 1H, H-1), 4.76 (d, J = 11 Hz, 1H, Bn), 4.66
(d, J = 11 Hz, 1H, Bn), 4.51 (d, J = 11 Hz, 1H, Bn), 4.50 (dd, J3,4
1.7 Hz, J4,5 = 2.5 Hz, 1H, H-4), 4.47 (d, J = 11 Hz, 1H, Bn), 4.37 (dt,
1,2 < 1 Hz, J2,3 = 1.1 Hz, J2,OH = 10.3 Hz, H-2), 3.99 (dd, J2,3 = 1.1 Hz,
=
J
J3,4 = 1.7 Hz, 1H, H-3), 3.77 (d, J = 10.3 Hz, 1H, OH), 3.74 (m, 1H, H-
5), 3.59 (dd, J4,5 = 2.5 Hz, J5,5′ = 10.5 Hz, 1H, H-5′), 2.35 (s, 3H, Tol).
13C NMR (100 MHz, CDCl3) δ = 137.56, 137.16, 136.92, 131.91,
129.70, 128.59, 128.49, 128.12, 127.89, 127.86, 127.82, 95.43 (C-1),
85.15, 83.42, 79.03, 73.82, 72.10, 69.63, 21.09. HR ESI-TOF MS (m/z):
calcd. for C26H28O4SNa [M + Na]+, 459.1601; found 459.1605.
4-Methylphenyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-3,5-
di-O-benzyl-1-thio-α-D-arabinofuranoside (6): The dried
5
1
(DCM/ethyl acetate = 8:1). H NMR (400 MHz, CDCl3) δ = 7.27–7.18
(438 mg, 1.01 mmol), 3 (635 mg, 1.15 mmol) and activated 4Å MS
(1 g) were mixed together in anhydrous DCM (4 mL). The mixture
was stirred for 1 h at RT under argon. BF3·Et2O (35 μL, 0.23 mmol)
was added and the reaction was left for 20 min at –50 °C. The
mixture was stirred at RT for 1 h before adding triethylamine. After
concentration the resulting crude product was purified by column
chromatography (cyclohexane/ethyl acetate = 4:1) getting com-
pound 6 (600 mg, 85 %) as colorless syrup. Rf = 0.4 (cyclohexane/
ethyl acetate = 2:1). 1H-NMR (400 MHz, CDCl3) δ = 7.46–7.28 (m,
12H, Ph), 7.14–7.07 (d, J = 9.58 Hz, 2H, Ph), 5.44 (d, J = 3.25 Hz, 1H,
H-1Ara-A), 5.11 (s, 1 H, H-1Ara-B), 5.04 (d, J = 1.60 Hz, 1H, H-2Ara-B),
4.97 (dd, J2,3 = 1.60 Hz, J3,4 = 5.14 Hz, 1H, H-3Ara-B), 4.20 (m, 1H,
H-4Ara-B ), 4.43–4.35 (m, 1H, H-5Ara-B), 4.30 (m, 1H, H-4Ara-A), 4.27 (m,
1H, H-2Ara-A), 4.26–4.19 (m, 1H, H-5′Ara-B), 4.04 (m, 1H, H-3Ara-A), 3.61
(m, 2H, H-5Ara-A), 2.27 (s, 3H, Tol), 2.06 (s, 3H, Ac), 2.00 (s, 3H, Ac),
1.99 (s, 3H, Ac). 13C NMR (100 MHz, CHCl3) δ = 138.02, 137.65,
137.56, 132.44, 130.65, 129.67, 128.38, 127.83, 127.73, 127.66, 106.61
(C-1Ara-B), 91.10 (C-1Ara-A), 86.65, 83.11, 81.62, 80.63, 80.21, 73.34,
72.43, 68.99, 63.24, 26.93, 21.11, 20.75, 20.70. HR ESI-TOF MS (m/z):
calcd. for C37H42O11S [M + Na]+, 717.2340, found 717.2340.
(m, 10H, Ph), 5.26–5.11 (m, 3H), 4.99–4.97 (m, 2H, H-1Ara-A, H-1Ara-B),
4.70 (s, 1H, H-1Man), 4.97–4.96 (m, 1H), 4.94–4.92 (m, 1H), 4.52 (d,
J = 11.8 Hz, 2H, Bn), 4.47 (d, J = 11.8 Hz, 1H, Bn), 4.45 (d, J = 11.8 Hz,
1H, Bn), 4.33–4.28 (m, 1H), 4.21–4.11 (m, 4H), 3.87–3.67 (m, 4H),
3.59–3.52 (m, 2H), 3.51–3.34 (m, 2H, CH2), 3.28 (t, J = 6.7 Hz, 2H,
CH2), 2.03 (s, 3H, Ac), 2.02 (s, 3H, Ac), 1.99 (s, 3H, Ac), 1.98 (s, 3H,
Ac), 1.94 (s, 3H, Ac), 1.92 (s, 3H, Ac), 1.75–1.70 (m, 2H, CH2). 13C NMR
(100 MHz, CDCl3) δ = 170.45, 170.14, 170.03, 169.95, 169.70, 169.57,
138.06, 137.84, 128.33, 128.31, 127.75, 127.73, 127.69, 127.63, 106.46
(C-1Ara-A), 105.31 (C-1Ara-B), 97.41 (C-1Man), 86.52, 83.43, 81.76, 80.77,
80.41, 76.86, 73.34, 72.13, 69.64, 69.59, 69.42, 69.33, 66.99, 66.18,
64.73, 63.06, 48.19, 28.60, 20.80, 20.76, 20.73, 20.71, 20.69. HR ESI-
TOF MS (m/z): calcd. for C45H57N3O20NH4 [M + NH4]+, 977.3880;
found 977.3874.
4-Methylphenyl (2,3,4-Tri-O-acetyl-α-D-arabinofuranosyl)-
(1→2)-(3,5-di-O-benzyl-α-D-arabino-furanosyl)-(1→6)-2,3,4-tri-
O-acetyl-1-thio-α-D-mannopyranoside (15): The dried 11 (50 mg,
0.068 mmol), 13 (45 mg, 0.11 mmol) and activated 4Å MS (100 mg)
were mixed together in anhydrous Et2O (1.5 mL) stirred for 1 h at
RT under argon. Then BF3·Et2O (10 μL, 0.07 mmol) was added and
the reaction was left for 1 h at –30 °C before quenching by triethyl-
amine. After filtering by Celite and concentration, the resulting
crude product was purified by column chromatography (DCM/ethyl
3-Azidopropyl 2,3,4-Tri-O-acetyl-α-D-mannopyranoside (9): The
enzymatic hydrolysis of compound 8 (0.45 g, 1.04 mmol) was car-
ried out in 50 mM KH2PO4 buffer pH 4 containing 30 % acetonitrile
for complete solubilisation of the substrate (104 mL) under mag-
netic stirring. The reactions started after addition of the immobi- acetate = 8:1) getting 15 (36 mg, 60 %) as colorless syrup. Rf = 0.5
lized CRL (3 g, 1400 IU/g). During the reaction pH value was main- (cyclohexane/ethyl acetate = 3:2). 1H NMR (400 MHz, CDCl3) δ =
tained constant. The course of the hydrolysis was monitored by TLC. 7.32 (d, J = 8.4 Hz, 2H, Ph), 7.26–7.19 (m, 10H, Ph), 7.02 (d, J =
After 24 h the reaction was stopped by biocatalyst filtration and
8.4 Hz, 2H, Ph), 5.38 (m, 1H), 5.30 (d, J = 1.43 Hz, 1H, H-1Man), 5.27–
the reaction mixture was extracted with ethyl acetate. After evapo- 5.21 (m, 2H), 4.98 (s, 1H, H-1Ara-A), 4.97 (s, 1H, H-1Ara-B), 4.96–4.92
ration of the solvent under reduced pressure the residue was puri-
fied by flash chromatography to obtain the product 9 (0.347 g,
85 %). Rf = 0.25 (cyclohexane/ethyl acetate = 4:1). 1H NMR
(400 MHz, CDCl3) δ = 5.37 (dd, J2,3 = 3.5 HZ, J3,4 = 8.6 Hz, 1H, H-3),
5.26–5.20 (m, 2H, H-2, H-4), 4.82 (d, J = 1.6 Hz, 1H, H-1), 3.84–3.65
(m, 2H, H-5, H-6), 3.66–3.47 (m, 2H, CH2), 3.42 (t, J = 6.19 Hz, 2H,
CH2), 2.38–2.34 (m, 1H, OH), 2.14 (s, 3H, Ac); 2.07 (s, 3H, Ac), 2.00 (s,
(m, 2H), 4.55 (d, J = 11.8 Hz, Bn), 4.53–4.46 (m, 3H, Bn), 4.45–4.44
(m, 1H), 4.27 (dd, J1 = 3.2 Hz, J2 = 11.1 Hz, 1H), 4.17–4.11 (m, 4H),
3.86–3.81 (m, 2H), 3.59–3.48 (m, 3H); 2.18 (s, 3H, CH3), 2.02 (s, 3H,
CH3), 1.98 (s, 3H, CH3), 1.97 (s, 3H, CH3), 1.96 (s, 3H, CH3), 1.94 (s,
3H, CH3). 13C NMR (100 MHz, CDCl3) δ = 170.46, 170.05, 170.03,
169.89, 169.72, 169.58, 138.27, 138.05, 137.88, 132.71, 129.92,
129.29, 128.33, 128.31, 127.76, 127.74, 127.66, 127.62, 106.51 (C-
3H, Ac), 1.92–1.83 (m, 2H, CH2). 13C NMR (100 MHz, CDCl3) δ = 1Ara-A), 105.37 (C-1Ara-B), 86.93 (C-1Man), 86.29, 83.25, 81.78, 80.45,
170.79, 170.08, 169.88, 97.69 (C-1), 70.80, 69.56, 68.83, 66.41, 64.78,
80.42, 73.34, 72.15, 71.12, 70.28, 69.68, 69.37, 67.20, 66.30, 63.06,
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21.05, 20.80, 20.78, 20.72, 20.69. HR ESI-TOF MS (m/z): calcd. for and evporation. The resulting product was purified by column chro-
C49H58O19 SNH4 [M + NH4]+, 1000.3631; found 1000.3636.
matography (cyclohexane/ethyl acetate = 3:2). Compound 18 was
gotten (160 mg, 66 %) as white foam. Rf = 0.35 (cyclohexane/ethyl
acetate = 3:2). 1H NMR (400 MHz, CDCl3) δ = 5.47 (d, J = 2.5 Hz, 1H,
H-1), 5.30 (t, J = 2.5 Hz, 1H, H-2), 5.12 (m, 1H, H-3), 4.35 (m, 1H, H-
4), 3.93–3.79 (m, 2H, H-5, H-5′), 2.34 (s, 3H, Tol), 2.14 (s, 3H, Ac), 2.09
(s, 3H, Ac), 2.02–1.99 (m, 1H, OH). 13C NMR (100 MHz, CDCl3) δ =
170.46, 169.67, 138.16, 132.83, 129.85, 129.58, 91.10 (C-1), 82.59,
81.71, 77.08, 61.57, 21.14, 20.81, 20.76. HR ESI-TOF MS (m/z): calcd.
for C16H20O6SNa [M + Na]+, 363.0873; found 363.0880.
3-Azidopropyl (2,3,4-Tri-O-acetyl-α-D-arabinofuranosyl)-(1→2)-
(3,5-di-O-benzyl-α-D-arabino-furanosyl)-(1→6)-(2,3,4-tri-O-
acetyl-α-D-mannopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-α-D-
mannopyranoside (15′): The dried 15 (21 mg, 0.021 mmol), 9
(14 mg, 0.034 mmol) and activated 4Å MS (100 mg) were mixed
together in anhydrous DCM (1.5 mL) stirred for 1 h at RT under
argon. Then NIS (14 mg, 0.063 mmol) and TMSOTf (6 μL, 0.03 mmol)
were added and the reaction was left for 1 h at –10 °C before
filtering by Celite, then the solution was washed with saturated aq.
Na2S2O3, NaHCO3, water and dried with MgSO4. After concentration,
the resulting crude product was purified by column chromatogra-
phy (cyclohexane/ethyl acetate = 1:1) getting 15′ (20 mg, 78 %) as
4-Methylphenyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-
(1→2)-(3,5-di-O-benzyl-α-D-arabinofuranosyl)-(1→5)-2,3-di-O-
acetyl-1-thio-α-D-arabinofuranoside (19): The dried 11 (270 mg,
0.37 mmol), 18 (189 mg, 0.56 mmol) and activated 4Å MS (500 mg)
were mixed together in anhydrous Et2O (6 mL). The mixture was
stirred for 1 h at RT. BF3·Et2O (13 μL, 0.1 mmol) was added and the
reaction was left for 1 h at –30 °C before adding triethylamine and
being filtered through Celite. After concentration the resulting
crude product was purified by column chromatography twice (cy-
clohexane/ethyl acetate = 1:1 and DCM/ethyl acetate = 10:1). 19
(197 mg, 58 %) was gotten as white foam. Rf = 0.5 (cyclohexane/
1
colorless syrup. Rf = 0.5 (cyclohexane/ethyl acetate = 1:2). H NMR
(400 MHz, CDCl3) δ = 7.34–7.23 (m, 10H, Ph), 5.33–5.29 (m, 3H),
5.26–5.22 (m, 3H), 5.07 (s, 1H, H-1Ara-B), 5.05 (s, 1H, H-1Ara-A), 5.04 (d,
J = 1.7 Hz, 1H), 5.00 (dd, J1 = 1.3 Hz, J2 = 4.9 Hz, 1H), 4.85 (s, 1H, H-
1Man-A), 4.77 (s, 1H, H-1Man-B), 4.61 (d, J = 11.8 Hz, 1H, Bn), 4.58 (d,
J = 11.8 Hz, 1H, Bn), 4.55 (d, J = 11.8 Hz, 1H, Bn), 4.53 (d, J = 11.8 Hz,
1H, Bn), 4.38 (d, J = 9.5 Hz, 1H), 4.27–4.19 (m, 4H), 3.99 (m, 1H),
3.90–3.79 (m, 5H), 3.66–3.49 (m, 5H), 3.42 (t, J = 6.3 Hz, 2H), 2.14 (s,
3H, Ac), 2.10 (s, 3H, Ac), 2.10 (s, 3H, Ac), 2.06 (s, 3H, Ac), 2.04 (s, 3H,
Ac), 2.04 (s, 3H, Ac), 2.00 (s, 3H, Ac), 1.99 (s, 3H, Ac), 1.98 (s, 3H, Ac),
1.91–1.88 (m, 2H). 13C NMR (100 MHz, CDCl3) δ = 170.49, 170.19,
170.11, 170.06, 169.89, 169.80, 169.74, 169.63, 169.57, 138.05,
137.85, 128.33, 128.31, 127.78, 127.74, 106.49 (C-1Ara-B), 105.27 (C-
1Ara-A), 97.40 (C-1Man-A, C-1Man-B), 86.46, 83.31, 81.77, 80.78, 80.41,
77.22, 76.89, 73.36, 72.07, 69.56, 69.51, 69.32, 69.23, 69.20, 66.83,
66.49, 66.39, 65.98, 64.92, 63.13, 48.20, 28.67, 20.80, 20.78, 20.75,
20.70. HR ESI-TOF MS (m/z): calcd. for C57H73N3O28Na [M + Na]+,
1270.4273; found 1279.4230.
1
ethyl acetate = 1:1). H NMR (400 MHz, CDCl3) δ = 7.42–7.37 (d, J =
7.9 Hz, 2H, Ph), 7.35–7.27 (m, 10H, Ph), 7.12–7.07 (d, J = 7.9 Hz, 2H,
Ph), 5.44 (d, J = 1.4 Hz, 1H, H-1Ara-A), 5.22–5.20 (m, 2H), 5.10 (s, 1H,
H-1Ara-C), 5.04 (s, 1 H, H-1Ara-B), 5.03 (m, 1H), 4.99 (m, 1H), 4.60–4.50
(m, 4H, Bn), 4.44–4.19 (m, 6H), 4.01–3.96 (dd, J1 = 4.3 Hz, J2
=
11.1 Hz, 1H), 3.92–3.89 (dd, J1 = 2.6 Hz, J2 = 6.1 Hz, 1H), 3.75–3.70
(dd, J1 = 3.7 Hz, J2 = 11.2 Hz, 1H), 3.66–3.57 (m, 2H), 2.31 (s, 3H,
Tol), 2.10 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.04 (s, 3H, Ac),
2.01 (s, 3H, Ac). 13C NMR (100 MHz, CDCl3) δ = 170.47, 170.06, 169.
91, 169.76, 169. 57, 139.08, 138.88, 138.78, 132.72, 129.74, 128.33,
127.70, 127.75, 127.74, 127.69, 127.61; 106.55 (C-1Ara-C), 106.38 (C-
1Ara-B), 90.84 (C-1Ara-A), 86.72, 83.16, 81.69, 80.78, 80.46, 77.22, 76.86,
73.32, 72.09, 69.49, 65.91, 63.13, 21.1, 20.77, 20.73, 20.72, 20.69,
20.68. HR ESI-TOF MS (m/z): calcd. for C46H54O17SNa [M + Na]+,
933.2974; found 933.2979.
2,3,4-Tri-O-acetyl-α-D-arabinofuranosyl-(1→2)-3,5-di-O-benzyl-
α-D-arabino-furanosyl-(1→6)-1,2,3,4-tetra-O-acetyl-α-D-manno-
pyranoside (16): The dried 11 (50 mg, 0.068 mmol), 14 (39 mg,
0.11 mmol) and activated 4Å MS (100 mg) were mixed together in
anhydrous Et2O (1.5 mL). The mixture was stirred for 1 h at RT under
argon. BF3·Et2O (10 μL, 0.07 mmol) was added and the reaction was
left for 20 min at –30 °C before quenching by triethylamine. After
filtering by Celite and concentration, the resulting crude product
was purified by column chromatography (DCM/ethyl acetate = 8:1)
getting 16 (41 mg, 65 %) as colorless syrup. Rf = 0.45 (cyclohexane/
ethyl acetate = 1:1). 1H NMR (400 MHz, CDCl3) δ = 7.33–7.24 (m,
10H), 6.06 (d, J = 1.9 Hz, 1H, H-1Man), 5.38–5.34 (m, 4H), 5.22 (m,
1H), 5.03 (m, 1H), 5.04 (s, 1H, H-1Ara-B), 5.02 (s, 1H, H-1Ara-A), 5.00 (m,
1H), 4.61 (d, J = 11.8 Hz, 1H, Bn), 4.58 (d, J = 11.8 Hz, 1H, Bn), 4.55–
4.51 (m, 2H, Bn), 4.38 (d, J = 8.4 Hz, 1H), 4.26–4.19 (m, 4H), 4.01 (m,
1H), 3.89 (dd, J1 = 2.5 Hz, J2 = 6.4 Hz, 1H), 3.84 (dd, J1 = 4.3 Hz, J2 =
11 Hz, 1H), 3.65–3.56 (m, 3H), 2.12 (s, 3H, CH3), 2.10 (s, 3H, CH3),
2.09 (s, 3H, CH3), 2.08 (s, 3H, CH3), 2.05 (s, 3H, CH3), 2.01 (s, 3H, CH3),
2.00 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3) δ = 170.49, 170.05,
169.85, 169.57, 169.48, 168.15, 138.05, 137.84, 128.33, 128.31,
127.76, 127.74, 127.67, 127.63, 106.60 (C-1Ara-B), 105.31 (C-1Ara-A),
90.56 (C-1Man), 86.53, 83.25, 81.75, 80.61, 80.41, 76.84, 73.33, 72.10,
71.23, 69.50, 68.99, 68.43, 66.63, 66.27, 63.04, 20.83, 20.72, 20.70,
20.68. HR ESI-TOF MS (m/z): calcd. for C44H54O21NH4 [M + NH4]+,
936.3499; found 936.3496.
4-Methylphenyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-
(1→2)-(3,5-di-O-benzyl-ꢀ-D-arabinofuranosyl)-(1→5)-2,3-di-O-
acetyl-1-thio-α-D-arabinofuranoside (20): The dried 11 (270 mg,
0.37 mmol), 18 (189 mg, 0.56 mmol) and activated 4Å MS (500 mg)
were mixed together in anhydrous Et2O (6 mL). The mixture was
stirred for 1 h at RT. BF3·Et2O (13 μL, 0.1 mmol) was added and the
reaction was left for 1 h at –30 °C before adding triethylamine and
being filtered through Celite. After concentration the resulting
crude product was purified by column chromatography twice (cy-
clohexane/ethyl acetate = 1:1 and DCM/ethyl acetate = 10:1). 20
(98 mg, 29 %) was gotten as white foam. Rf = 0.5 (cyclohexane/
1
ethyl acetate = 1:1). H-NMR (400 MHz, CDCl3) δ = 7.40–7.38 (d, J =
8.0 Hz, 2H), 7.30–7.25 (m, 10H), 7.10–7.08 (d, J = 7.9 Hz, 2H), 5.39
(s, 1H, H-1Ara-A), 5.24 (t, J = 5.2 Hz, 1H), 5.13 (d, J = 2.3 Hz, 1H), 5.10
(s, 1H, H-1Ara-C); 5.06–5.03 (m, 2H), 5.00 (d, J = 3.5 Hz, H-1Ara-B), 4.70–
4.44 (m, 4H, Bn), 4.43–4.33 (m, 3H), 4.22–4.04 (m, 4H), 4.01–3.97 (dd,
J1 = 3.3 Hz, J2 = 10.4 Hz, 1H), 3.66–3.55 (m, 3H), 2.30 (s, 3H, Tol),
2.12 (s, 3H, Ac), 2.07 (s, 3H, Ac), 2.05 (s, 3H, Ac), 2.04 (s, 3H, Ac), 1.99
(s, 3H, Ac). 13C NMR (100 MHz, CDCl3) δ = 170.44, 170.21, 169.79,
169.73, 169.66, 138.20, 138.16, 138.08, 132.79, 129.82, 129.68,
128.33, 128.32, 127.67, 127.56, 127.55, 127.47, 106.93 (C-1Ara-C),
101.45 (C-1Ara-B), 90.90 (C-1Ara-A), 84.50, 82.15, 82.06, 81.82, 81.47,
79.73, 79.19, 77.46, 76.79, 73.22, 72.65, 72.03, 66.24, 63.03, 21.09,
20.77, 20.74, 20.70, 20.67, 20.57. HR ESI-TOF MS (m/z): calcd. for
C46H54O17SNa [M + Na]+, 933.2974; found 933.2978.
4-Methylphenyl 2,3-Di-O-acetyl-1-thio-α-D-arabinofuranoside
(18): Compound 17 (280 mg, 0.72 mmol) was dissolved in DCM
(6 mL) with p-thiocresol (142 mg, 0.86 mmol). Then BF3·Et2O
(230 μL, 1.28 mmol) was added to the solution at 0 °C and the
mixture was stirred for 1 h before being quenched by triethylamine
3-Azidopropyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-(1→2)-
(3,5-di-O-benzyl-α-D-arabinofuranosyl)-(1→5)-(2,3-di-O-acetyl-
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α-D-arabinofuranosyl)-(1→6)-2,3,4-tri-O-acetyl-α-D-mannopyr-
uct was purified by column chromatography (cyclohexane/ethyl
anoside (21): The dried 19 (80 mg, 0.088 mmol), 9 (52 mg, acetate = 3:1) getting compound 24 (263 mg, 90 %) as colorless
0.13 mmol) and activated 4Å MS (200 mg) were mixed together in
anhydrous DCM (4 mL) for 1 h at RT. The reaction was put at –10 °C
for 5 min before NIS and AgOTf were added. Upon for stirring at
–10 °C for 1 h, the reaction was diluted with CH2Cl2, After filtering
by Celite, the organic phase was washed with saturated aq.
Na2S2O3, water and dried with MgSO4, and then concentrated un-
der reduced pressure. The residue was finally purified bysilica gel
column chromatography with cyclohexane/ethyl acetate (2:3) as the
eluent to afford 21 (84 mg, 82 %) as foamy solid. Rf = 0.25 (cyclohex-
syrup. Rf = 0.5 (cyclohexane/ethyl acetate = 2:1). 1H NMR (400 MHz,
CDCl3) δ = 7.27–7.18 (m, 13H, Ph), 7.12–7.09 (m, 2H, Ph), 5.23 (s, 1H,
H-1Ara), 5.21–5.14 (m, 3H), 4.83 (dd, J1 = 1.7 Hz, J2 = 5.3 Hz, 1H),
4.82 (d, J = 1.60 Hz, 1H, H-1Man-B), 4.77 (d, J = 11 Hz, 1H), 4.69 (d,
J = 1.40 Hz, 1H, H-1Man-A), 4.61–4.50 (m, 6H, Bn), 4.35–4.11 (m, 3H),
4.00 (s, 1H), 3.84–3.63 (m, 8H), 3.46 (dd, J1 = 2.4 Hz, J2 = 10.9 Hz,
1H), 3.43–3.29 (m, 3H), 2.03 (s, 3H, Ac), 2.02 (s, 3H, Ac), 1.96 (s, 3H,
Ac), 1.94 (s, 3H, Ac), 1.92 (s, 3H, Ac), 1.89 (s, 3H, Ac), 1.80–1.74 (m,
2H, CH2). 13C NMR (100 MHz, CDCl3) δ = 170.52, 170.20, 170.05,
ane/ethyl acetate = 1:1). 1H NMR (400 MHz, CDCl3) δ = 7.32–7.26 169.93, 169.62, 169.30, 138.50, 138.44, 138.31, 128.34, 128.26,
(m, 10H), 5.30–5.28 (m, 2H), 5.21–5.20 (m, 1H), 5.11 (s, 1H, H-1Ara-A), 127.90, 127.73, 127.57, 127.54, 127.42, 106.82 (C-1Ara), 99.19
5.09–4.99 (m, 4H), 5.05 (m, 2H, H-1Ara-B, H-1Ara-C), 4.80 (d, J = 1.6 Hz, (C-1Man-B), 97.45 (C-1Man-A), 81.16, 80.30, 79.96, 74.98, 74.60, 73.93,
1H, H-1Man), 4.59 (d, J = 11.8 Hz, 1H, Bn), 4.58 (d, J = 11.8 Hz, 1H,
Bn), 4.53 (d, J = 11.8 Hz, 1H, Bn), 4.52 (d, J = 11.8 Hz, 1H, Bn), 4.38–
4.35 (m, 1H), 4.27–4.19 (m, 5H), 3.97–3.79 (m, 5H), 3.71–3.49 (m, 5H),
3.41 (t, J = 6.6 Hz, 2H), 2.14 (s, 3H, Ac), 2.09 (s, 3H, Ac), 2.09 (s, 3H,
Ac), 2.07 (s, 3H, Ac), 2.05 (s, 3H, Ac), 2.02 (s, 3H, Ac), 2.00 (s, 3H, Ac),
1.98 (s, 3H, Ac), 1.89–1.86 (m, 2H, CH2). 13C NMR (100 MHz, CDCl3)
δ = 170.47, 170.09, 170.07, 169.95, 169.68, 169.64, 169.57, 138.08,
137.77, 128.32, 127.75, 106.56 (C-1Ara-C), 105.31 (C-1Ara-B), 105.25 (C-
1Ara-A), 97.46, 86.59, 83.11, 81.76, 81.44, 81.39, 80.79, 80.46, 76.88,
73.33, 72.05, 69.64, 69.52, 69.31, 69.27, 66.52, 66.05, 65.45, 64.72,
63.12, 48.17, 28.70, 20.86, 20.74, 20.72, 20.70. HR ESI-TOF MS (m/z):
calcd. for C54H69N3O26Na [M + Na]+, 1198.4062; found 1198.4057.
73.27, 72.24, 71.91, 69.62, 69.39, 69.23, 66.71, 66.06, 64.68, 63.05,
48.14, 28.63, 20.84, 20.77, 20.76, 20.71, 20.62. HR ESI-TOF MS (m/z):
calcd. for C45H50O12SNa [M + Na]+, 837.2915; found 837.2918.
Cyanomethyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-(1→2)-
(3,4,6-tri-O-benzyl-α-D-mannopyranosyl)-(1→6)-2,3,4-tri-O-
acetyl-1-thio-α-D-mannopyranoside (28): To a solution of 24
(260 mg, 0.32 mmol) in 7 mL of wet CH2Cl2 (containing 20 % H2O)
was added NIS (144 mg, 0.64 mmol), AgOTf (82 mg, 0.32 mmol)
and TTBP (238 mg, 2.58 mmol). The solution was stirred for 1 h
until no 24 left. The solution was diluted with CH2Cl2, and after
filtering by Celite, the organic phase was washed with saturated aq.
Na2S2O3, water and dried with MgSO4, then concentrated under
reduced pressure. The crude was purified by column chromatogra-
phy (cyclohexane/ethyl acetate = 3:2) to give 25 (192 mg, 85 %) as
colorless syrup. Rf = 0.25 (cyclohexane/ethyl acetate = 3:2). All the
25 was immediately put into 3 mL of dry DCM under argon and
then CCl3CN (270 μL, 2.7 mmol) and DBU (41 μL, 0.27 mmol) were
added to the solution at ice bath. The solution was stirred for 1 h
at 0 °C and solution was removed under vacuo and purified by
column chromatography with 1 % triethylamine added cyclohex-
ane/ethyl acetate (2:1). 26 (207 mg, 90 %) was gotten as colorless
syrup. Rf = 0.5 (cyclohexane/ethyl acetate = 3:2). 26 should be used
without delay for its poor stability. The dried 26 (50 mg,
0.058 mmol), 27 (33 mg, 0.09 mmol) and activated 4Å MS (200 mg)
were mixed together in 3 mL of anhydrous Et2O and DCM solution
(15:1). The mixture was stirred for 1 h at RT under argon then cooled
to –30 °C. Then BF3·Et2O (26 μL, 0.18 mmol) was added and the
reaction was left for 3 h at –30 °C before being quenched with
triethylamine. After Celite filter and concentration the resulting
crude product was purified by column chromatography (cyclohex-
ane/ethyl acetate = 1:1) getting compound 28 (28 mg, 45 %) as
3-Azidopropyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-(1→2)-
(3,5-di-O-benzyl-ꢀ-D-arabinofuranosyl)-(1→5)-(2,3-di-O-acetyl-
α-D-arabinofuranosyl)-(1→6)-2,3,4-tri-O-acetyl-α-D-mannopyr-
anoside (22): The dried 20 (40 mg, 0.044 mmol), 9 (26 mg,
0.065 mmol) and activated 4Å MS (100 mg) were mixed together
in anhydrous DCM (3 mL) for 1 h at RT. The reaction was put at
–10 °C for 5 min before NIS and AgOTf were added. Upon for stirring
at –10 °C for 1 h, the reaction was diluted with CH2Cl2, After filtering
by Celite, the organic phase was washed with saturated aq.
Na2S2O3, water and dried with MgSO4, and then concentrated un-
der reduced pressure. The residue was finally purified bysilica gel
column chromatography with cyclohexane/ethyl acetate (2:3) as the
eluent to afford 21 (43 mg, 84 %) as foamy solid. Rf = 0.25 (cyclohex-
ane/ethyl acetate = 1:1). 1H NMR (400 MHz, CDCl3) δ = 7.43–7.26
(m, 10H, Ph), 5.20–5.10 (m, 3H ), 5.34–5.30 (m, 2H), 5.08 (s, 1H,
H-1Ara-C ), 5.03 (dd, J1 = 1.8 Hz, J2 = 6.7 Hz, 1H), 4.99 (d, J = 3.3 Hz,
1H), 4.95 (s, 1H, H-1Ara-B), 4.87 (d, J = 4.3 Hz, 1H), 4.81 (d, J = 1.3 Hz,
1H, H-1Man), 4.65–4.52 (m, 4H, Bn), 4.50–4.36 (m, 2H), 5.23–3.99 (m,
6H), 3.88–3.76 (m, 3H), 3.62–3.49 (m, 5H), 3.41 (t, J = 6.5 Hz, 2H,
CH2), 2.13 (s, 3H, Ac), 2.12 (s, 3H, Ac), 2.09 (s, 3H, Ac), 2.07 (s, 3H,
Ac), 2.07 (s, 3H, Ac), 1.98 (s, 3H, Ac), 1.97 (s, 3H, Ac), 1.96 (s, 3H, Ac),
1.89–1.85 (m, 2H, CH2). 13C NMR (100 MHz, CDCl3) δ = 170.50,
170.15, 170.05, 170.00, 169.94, 169.74, 169.58, 169.50, 138.30,
138.14, 128.36, 128.31, 127.67, 127.47, 106.92 (C-1Ara-C), 105.38 (C-
1Ara-B), 101.44 (C-1Ara-A), 97.52 (C-1Man), 84.73, 82.60, 82.23, 82.09,
80.68, 79.65, 79.15, 73.24, 72.68, 71.86, 69.64, 69.36, 69.33, 66.95,
66.30, 65.11, 64.74, 62.79, 48.11, 28.68, 20.80, 20.75, 20.70, 20.67,
20.58, 20.56. HR ESI-TOF MS (m/z): calcd. for C54H69N3O26Na [M +
Na]+, 1198.4062; found 1198.4059.
1
colorless syrup. Rf = 0.4 (cyclohexane/ethyl acetate = 3:2). H NMR
(400 MHz, CDCl3) δ = 7.28–7.18 (m, 13H, Ph), 7.15–7.12 (m, 2H, Ph),
5.34 (d, J = 1.1 Hz, 1H, H-1Man-A), 5.28 (dd, J1 = 1.5Hz, J2 = 3.4 Hz,
1H), 5.24 (s, 1H, H-1Ara), 5.21–5.20 (m, 1H), 5.13–5.10 (m, 1H), 4.91
(dd, J1 = 1.6Hz, J2 = 5.2 Hz, 1H), 4.83 (d, J = 1.7 Hz, H-1Man-B), 4.79
(d, J = 11 Hz, 1H), 4.64–4.43 (m, 6H, Bn), 4.43 (dd, J1 = 3.7 Hz, J2 =
11.8 Hz, 1H), 4.23–4.12 (m, 3H), 4.00 (t, J = 2.2 Hz, 1H), 3.84–3.75
(m, 3H), 3.52 (dd, J1 = 2.3 Hz, J2 = 11.2 Hz, 1H), 3.25 (d, J = 16.9 Hz,
1H, CH2), 3.05 (d, J = 16.9 Hz, 1H, CH2), 2.06 (s, 3H, Ac), 2.03 (s, 3H,
4-Methylphenyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)- Ac), 1.98 (s, 3H, Ac), 1.96 (s, 3H, Ac), 1.93 (s, 3H, Ac), 1.90 (s, 3H, Ac).
(1→2)-3,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside (24): The
13C NMR (100 MHz, CDCl3) δ = 170.56, 170.21, 169.78, 169.66,
dried 23 (200 mg, 0.36 mmol), 3 (227 mg, 0.54 mmol) and activated 169.46, 169.30, 138.46, 128.38, 128.36, 128.28, 127.88, 127.74,
4Å MS (500 mg) were mixed together in anhydrous DCM (6 mL).
The mixture was stirred for 1 h at RT under argon then cooled to
–50 °C. BF3·Et2O (77 μL, 0.54 mmol) was added and the reaction
was left for 20 min at –50 °C before adding triethylamine and being
127.59, 127.55, 127.47, 115.69, 106.84 (C-1Ara), 99.17 (C-1Man-B),
82.00 (C-1Man-A), 81.12, 80.36, 79.55, 74.97, 74.52, 73.83, 73.28, 72.07,
72.00, 70.62, 69.64, 69.42, 69.20, 66.42, 65.63, 63.02, 20.80, 20.73,
20.69, 20.63, 20.57, 15.30. HR ESI-TOF MS (m/z): calcd. for
filtered through Celite. After concentration the resulting crude prod- C52H61NO20SNa [M + Na]+ 1074.3400; found 1074.3403.
Eur. J. Org. Chem. 0000, 0–0
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3-Azidopropyl (2,3,5-Tri-O-acetyl-α-D-arabinofuranosyl)-(1→2)- 3-Aminopropyl α-D-Arabinofuranosyl-(1→2)-α-D-arabinofur-
(3,4,6-tri-O-benzyl-α-D-mannopyranosyl)-(1→6)-2,3,4-tri-O-
acetyl-α-D-mannopyranoside (29): The dried 26 (50 mg,
0.058 mmol), 9 (35 mg, 0.09 mmol) and activated 4Å MS (200 mg)
were mixed together in 3 mL of anhydrous DCM. The mixture was
stirred for 1 h at RT under argon then cooled to –30 °C. Then
BF3·Et2O (26 μL, 0.18 mmol) was added and the reaction was left
for 3 h at –30 °C before being quenched with triethylamine. After
Celite filter and concentration the resulting crude product was puri-
anosyl-(1→5)-α-D-arabinofuranosyl-(1→6)-α-D-mannopyranos-
ide (32): To a solution of compound 21 (42 mg) in THF (4 mL) and
methanol (0.1 mL), liquid NH3 (8 mL) was added at –60 °C, a piece
of sodium was added quickly until the solution became dark blue.
After 30 min, few drops of water were added to the solution to
quench the reaction. And the crude was evaporated and resolve in
water. Then resin was added to the solution until pH reached 7.
After that the resin was filtered and washed by 1
M
NH3·H2O (50 mL
fied by column chromatography twice (cyclohexane/ethyl acetate = × 3). The NH3·H2O was collected and evaporated to give the crude.
1:1) getting compound 29 (47 mg, 75 %) as colorless syrup. Rf = 0.6
(cyclohexane/ethyl acetate = 1:1). 1H NMR (400 MHz, CDCl3) δ =
7.27–7.18 (m, 13H, Ph), 7.12–7.09 (m, 2H, Ph), 5.23 (s, 1H, H-1Ara),
Finally, the crude was purified by LH-20 in methanol to give 32
(12 mg, 55 %) as write foam. 1H NMR (400 MHz, D2O) δ = 5.05 (s,
1H, H-1Ara-C), 5.04 (s, 1H, H-1Ara-B), 4.93 (d, J = 1.5 Hz, H-1Ara-A), 4.70
5.21–5.14 (m, 3H), 4.83 (dd, J1 = 1.7 Hz, J2 = 5.3 Hz, 1H), 4.82 (d, J = (s, 1H, H-1Man), 4.10–4.05 (m, 1H), 4.02–3.91 (m, 6H), 3.88–3.78 (m,
1.60 Hz, 1H, H-1Man-B), 4.77 (d, J = 11 Hz, 1H), 4.69 (d, J = 1.40 Hz,
4H), 3.76–3.56 (m, 11H), 3.50–3.40 (m, 1H), 2.99–2.89 (m, 2H, CH2),
1H, H-1Man-A), 4.61–4.50 (m, 6H, Bn), 4.35–4.11 (m, 3H), 4.00 (s, 1H),
1.72–1.60 (m, 2H, CH2). 13C NMR (100 MHz, D2O) δ = 107.46
3.84–3.63 (m, 8H), 3.46 (dd, J1 = 2.4 Hz, J2 = 10.9 Hz, 1H), 3.43–3.29 (C-1Ara-C), 107.23 (C-1Ara-B), 106.29 (C-1Ara-A), 99.91 (C-1Man), 87.08,
(m, 3H), 2.03 (s, 3H, Ac), 2.02 (s, 3H, Ac), 1.96 (s, 3H, Ac), 1.94 (s, 3H,
Ac), 1.92 (s, 3H, Ac), 1.89 (s, 3H, Ac), 1.80–1.74 (m, 2H, CH2). 13C NMR
(100 MHz, CDCl3) δ = 170.52, 170.20, 170.05, 169.93, 169.62, 169.30,
138.50, 138.44, 138.31, 128.34, 128.26, 127.90, 127.73, 127.57,
127.54, 127.42, 106.82 (C-1Ara), 99.19 (C-1Man-B), 97.45 (C-1Man-A),
81.16, 80.30, 79.96, 74.98, 74.60, 73.93, 73.27, 72.24, 71.91, 69.62,
69.39, 69.23, 66.71, 66.06, 64.68, 63.05, 48.14, 28.63, 20.84, 20.77,
20.76, 20.71, 20.62. HR ESI-TOF MS (m/z): calcd. for C53H65N3O21Na
[M + Na]+, 1102.4003; found 1102.4009.
84.07, 83.19, 82.13, 82.06, 81.27, 80.78, 76.67, 76.47, 75.08, 71.17,
71.12, 70.58, 70.04, 69.96, 66.96, 66.75, 66.67, 66.57, 65.75, 65.50,
61.12, 60.83, 38.35, 29.27, 23.29. HR ESI-TOF MS (m/z): calcd. for
C
24H43NO18H [M + H]+, 634.2553, found 634.2552.
3-Aminopropyl α-D-Arabinofuranosyl-(1→2)-ꢀ-D-arabinofur-
anosyl-(1→5)-α-D-arabinofuranosyl-(1→6)-α-D-mannopyranos-
ide (33): To a solution of compound 22 (43 mg) in THF (4 mL) and
methanol (0.1 mL), liquid NH3 (8 mL) was added at –60 °C, a piece
of sodium was added quickly until the solution became dark blue.
After 30 min, few drops of water were added to the solution to
quench the reaction. And the crude was evaporated and resolve in
water. Then resin was added to the solution until pH reached 7.
3-Aminopropyl α-D-Arabinofuranosyl-(1→2)-α-D-arabinofur-
anosyl-(1→6)-α-D-mannopyranoside (30): To a solution of com-
pound 12 (45 mg) in THF (4 mL) and methanol (0.1 mL), liquid NH3
(8 mL) was added at –60 °C, a piece of sodium was added quickly
until the solution became dark blue. After 30 min, few drops of
water was added to the solution to quench the reaction. And the
After that the resin was filtered and washed by 1
M
NH3·H2O (50 mL
× 3). The NH3·H2O was collected and evaporated to give the crude.
Finally, the crude was purified by LH-20 in methanol to give 33
crude was evaporated and resolve in water. Then resin was added (12 mg, 54 %) as write foam. 1H NMR (400 MHz, D2O) δ = 5.01–4.99
to the solution until pH reached 7. After that the resin was filtered
(m, 2H, H-1Ara-C, H-1Ara-A), 4.92 (d, J = 1.5 Hz, 1H, H-1Ara-B), 4.70 (s,
1H, H-1Man), 3.08–3.04 (m, 3H), 3.99–3.94 (m, 3H), 3.85–3.77 (m, 3H),
3.85–3.77 (m, 6H), 3.70–3.42 (m, 11H), 2.96–2.85 (m, 2H, CH2), 1.70–
1.62 (m, 2H, CH2). 13C NMR (100 MHz, D2O) δ = 108.72 (C-1Ara-C),
and washed by 1 NH3·H2O (50 mL × 3). The NH3·H2O was col-
M
lected and evaporated to give the crude. Finally, the crude was
purified by LH-20 in methanol to give 30 (15 mg, 59 %) as write
foam. 1H NMR (400 MHz, D2O) δ = 5.12 (s, 2H, H-1Ara-A, H-1Ara-B), 107.57 (C-1Ara-A), 101.25 (C-1Ara-B), 99.93(C-1Man), 83.64, 82.99, 82.71,
4.80 (s, 1H, H-1Man), 4.12–3.53 (m, 18H), 3.07–2.85 (m, 2H, CH2), 1.84– 82.63, 81.42, 81.21, 80.68, 80.65, 77.03, 76.69, 72.92, 71.20, 71.13,
1.72 (m, 2H, CH2). 13C NMR (100 MHz, D2O) δ = 107.24 (C-1Ara-A), 70.60, 70.07, 69.97, 68.34, 68.29, 66.80, 66.69, 66.57, 66.50, 65.78,
106.31 (C-1Ara-B), 99.85 (C-1Man), 87.17, 84.11, 83.12, 81.27, 76.50,
75.10, 71.29, 70.59, 69.96, 66.73, 65.87, 61.14, 60.84, 38.43, 29.30,
23.29. HR ESI-TOF MS (m/z): calcd. for C19H34NO14H [M + H]+,
502.2130; found 502.2128.
63.07, 61.01, 38.39, 29.31. HR ESI-TOF MS (m/z): calcd. for
C
24H43NO18H [M + H]+, 634.2553, found 634.2556.
3-Aminopropyl α-D-Arabinofuranosyl-(1→2)-α-D-arabinofur-
anosyl-(1→6)-α-D-mannopyranosyl-(1→6)-α-D-mannopyranos-
ide (34): To a solution of Compound 15′ (15 mg ) in THF (2 mL)
and methanol (0.05 mL), liquid NH3 (4 mL) was added at –60 °C, a
piece of sodium was added quickly until the solution became dark
blue. After 30 min, few drops of water was added to the solution
to quench the reaction. And the crude was evaporated and resolve
in water. Then resin was added to the solution until pH reached 7.
3-Aminopropyl α-D-Arabinofuranosyl-(1→2)-α-D-mannopyran-
osyl-(1→6)-α-D-mannopyranoside (31): To a solution of com-
pound 29 (47 mg) in THF (4 mL) and methanol (0.1 mL), liquid NH3
(8 mL) was added at –60 °C, a piece of sodium was added quickly
until the solution became dark blue. After 30 min, few drop of water
was added to the solution to quench the reaction. And the crude
was evaporated and resolve in water. Then resin was added to the After that the resin was filtered and washed by 1
M
NH3·H2O (25 mL
solution until pH reached 7. After that the resin was filtered and
× 3). The NH3·H2O was collected and evaporated to give the crude.
Finally, the crude was purified by LH-20 in methanol to give 34
(4.2 mg, 55 %) as write foam. H NMR (400 MHz, D2O) δ = 5.16 (s,
washed by 1 NH3·H2O (50 mL × 3). The NH3·H2O was collected
M
1
and evaporated to give the crude. Finally, the crude was purified
by LH-20 in methanol to give 31 (12 mg, 53 %) as write foam. 1H
NMR (400 MHz, D2O) δ = 5.10 (d, J = 1.6 Hz, 1H, H-1Ara), 4.97(s, 1H,
H-1Man-A), 4.79 (s, 1H, H-1Man-B ), 4.15–4.13 (m, 1H), 4.05–4.03 (m,
1H), 3.95–3.47 (m, 20H), 3.05–3.02 (m, 2H, CH2), 1.73–1.70 (m, 2H,
CH2). 13C NMR (100 MHz, D2O) δ = 109.38 (C-1Ara), 99.99 (C-1Man-A),
1H, H-1Ara-B), 5.15 (s, 1H, H-1Ara-A), 4.86 (s, 1H, H-1Man-A), 4.82 (s, 1H,
H-1Man-B), 4.13 (s, 1H), 4.08–4.03 (m, 4H), 3.95–3.91 (m, 6H), 3.82–
3.65 (m, 17H), 3.07–3.04 (m, 2H, CH2), 2.02–1.74 (m, 2H, CH2). 13C
NMR (100 MHz, D2O) δ = 107.15 (C-1Ara-B), 106.26 (C-1Ara-A), 100.00
(C-1Man-A), 99.58 (C-1Man-B), 87.05, 84.09, 83.19, 81.29, 76.52, 75.14,
98.74 (C-1Man-B), 83.58, 81.23, 77.47, 76.47, 72.68, 71.05, 70.27, 66.84, 70.98, 69.98, 66.68, 66.39, 65.69, 61.16, 60.89, 38.48, 29.35, 21.19. HR
65.88, 61.10, 60.75, 38.43, 29.31, 26.11. HR ESI-TOF MS (m/z): calcd.
ESI-TOF MS (m/z): calcd. for C25H45NO19H [M + H]+, 664.2664, found
664.2657.
for C20H37NO15Na [M + Na]+, 554.2055, found 554.2052.
Eur. J. Org. Chem. 0000, 0–0
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Acknowledgments
We thank the China Scholarship Council (CSC) for Ph.D. fellow-
ships to Zhihao LI and Changping ZHENG. Financial supports
from the Centre National de la Recherche Scientifique (CNRS)
and the Sorbonne Université in France are gratefully acknowl-
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Keywords: Carbohydrates · Lipoarabinomannan ·
Glycoconjugates · Glycosylation · Oligosaccharides
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Received: December 27, 2019
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Full Paper
Glycoconjugates
Z. Li, C. Zheng, M. Terreni,
T. Bavaro, M. Sollogoub,
Y. Zhang* ........................................... 1–13
A Concise Synthesis of Oligosacchar-
ides Derived From Lipoarabinoman-
nan (LAM) with Glycosyl Donors
Having a Nonparticipating Group at
C2
A convenient synthesis of oligosac- compared to make the stereoselective
charides derived from lipoarabino- construction of glycosidic bonds. Five
mannan (LAM) with glycosyl donors LAM analogues were obtained with
having a nonparticipating group at C2 amino group which can be used for
was achieved from top to bottom. Dif- conjugation with proteins.
ferent donors and acceptors were
DOI: 10.1002/ejoc.201901915
Eur. J. Org. Chem. 0000, 0–0
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