On the stereoselectivity of glycosidation of thiocyanates, thioimidates, and thioglycosides

Article abstract of DOI:10.1016/j.carres.2010.08.003

Comparative side-by-side glycosylation studies demonstrated that glycosyl thiocyanates, thioimidates, and thioglycosides provide comparative stereoselectivities in glycosylations. Very high α-stereoselectivity that was previously recorded for glycosyl thiocyanates can be achieved, but only if glycosyl acceptors are equipped with electron-withdrawing acyl substituents. Partially benzylated glycosyl acceptors provided relatively modest stereoselectivity, which was on a par with other common glycosyl donors. Accordingly, thioimidates and thioglycosides showed high stereoselectivity similarly to that of thiocyanates with different classes of acylated primary and secondary glycosyl acceptors.

Full text of DOI:10.1016/j.carres.2010.08.003

Carbohydrate Research 345 (2010) 2146–2150
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
On the stereoselectivity of glycosidation of thiocyanates, thioimidates,
and thioglycosides
⇑
Sophon Kaeothip, Steven J. Akins, Alexei V. Demchenko
Department of Chemistry and Biochemistry, University of Missouri – St. Louis, One University Boulevard, St. Louis, MO 63121, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 May 2010
Received in revised form 5 August 2010
Accepted 5 August 2010
Available online 10 August 2010
Comparative side-by-side glycosylation studies demonstrated that glycosyl thiocyanates, thioimidates,
and thioglycosides provide comparative stereoselectivities in glycosylations. Very high a-stereoselectiv-
ity that was previously recorded for glycosyl thiocyanates can be achieved, but only if glycosyl acceptors
are equipped with electron-withdrawing acyl substituents. Partially benzylated glycosyl acceptors pro-
vided relatively modest stereoselectivity, which was on a par with other common glycosyl donors.
Accordingly, thioimidates and thioglycosides showed high stereoselectivity similarly to that of thiocya-
nates with different classes of acylated primary and secondary glycosyl acceptors.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Glycosylation
Stereoselectivity
Protecting groups
Glycosyl donors
The stereocontrolled introduction of glycosidic linkages1,2 is
arguably the most challenging aspect in the synthesis of oligosac-
charides3–9 and glycoconjugates.10–12 While a 1,2-trans glycosidic
linkage can be usually stereoselectively obtained by using the
anchimeric assistance from the participatory neighboring substitu-
ent at C-2 (most commonly an ester13 or recently introduced picol-
inyl),14,15 the stereoselective formation of a 1,2-cis linkage still
remains a notable challenge,16 despite significant recent improve-
ments.17–19 In addition to the effect of protecting groups on the
glycosyl donor, a myriad of other factors is known to have effect
on the stereoselectivity of the chemical glycosylation;20 and the ef-
fect of conformation,21 solvent,22–24 temperature,25 metal coordi-
nation,26 steric hindrance,27,28 and remote participation29–31 are
only few to mention. It is commonly believed that a typical glyco-
sylation follows the unimolecular mechanism with the rate-deter-
mining step being the glycosyl acceptor attack on the intermediate
formed as a result of the leaving group departure.32 Nevertheless,
occasionally the effect of a leaving group itself may also have an
influence on the anomeric stereoselectivity. However, it is often
unclear whether this effect is a result of a bimolecular or close-
ion pair rather than the unimolecular displacement mechanism,
or other factors affecting this complex process.
ested in a possible influence that different leaving groups may have
on the outcome of glycosylations. While on a number of occasions
we managed to achieve very good to excellent stereoselectivities,
particularly with the SBox glycosides, these results have been occa-
sionally outshadowed by other classes of glycosyl donors. For
example, glycosyl thiocyanates that have been introduced two dec-
ades ago have proven to be very effective glycosyl donors for what
then appeared to be ‘stereospecific 1,2-cis glycosylations’.33 Indeed,
in a series of publications, Kochetkov et al., provided a convincing
case of the power of this class of glycosyl donors.33–37 Various hex-
ose and pentose 1,2-trans thiocyanate glycosyl donors were found
to provide 1,2-cis glycosides completely stereoselectively (or ste-
reospecifically, as quoted in the original literature) with the only
failure reported when the method was applied to the synthesis
of b-mannosides.38 Another attractive feature of this glycosylation
approach is that the activation could be performed in the presence
of a catalytic amount of promoter and at ambient temperature.
While tritylated acceptors were used in most of the reported
transformations, a complementary procedure involving unpro-
tected hydroxyl group was also developed.35 The major drawback
of this technique was modest yields obtained during both the syn-
thesis of glycosyl thiocyanates and glycosidations thereof. This
drawback was arguably related to the propensity of thiocyanates
to isomerize into the corresponding isothiocyanates. The latter
would remain inert under the glycosylation conditions leading to
average to modest yields, which could be further diminished by
the migration of acetyl substituents that have been used as pro-
tecting groups throughout the original reports. For example, when
As part of a program to develop new protocols for the stereo-
controlled glycosylation, we have been investigating various clas-
ses of sulfur-based leaving groups ranging from conventional
alkyl/aryl thioglycosides to relatively novel S-benzoxazolyl (SBox)
or S-thiazolinyl (STaz) thioimidates. In particular, we were inter-
we reacted 3,4,6-tri-O-acetyl-2-O-benzyl-b-
D-glucopyranosyl thio-
⇑
Corresponding author. Fax: +1 314 516 5342.
E-mail address: demchenkoa@umsl.edu (A.V. Demchenko).
cyanate 137 with glycosyl acceptor 239 in the presence of catalytic
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.08.003

S. Kaeothip et al. / Carbohydrate Research 345 (2010) 2146–2150
2147
amount (0.2 equiv) of triphenylmethyl perchlorate40 (TrClO4) in
in low efficiency.35 Although excellent stereoselectivity
(a/
1,2-dichloroethane (DCE) at ambient temperature, the correspond-
b = 10.2:1) was observed with the benzoylated glycosyl acceptor
10, the disaccharide 6 was obtained in only 45% yield (Table 1, en-
try 1). The reaction with the more reactive glycosyl acceptor 11
was more rapid (36 vs 48 h), which was also reflected in the im-
proved yield of disaccharide (69%) yet displayed twofold reduced
stereoselectivity (entry 2).
ing 1,2-cis-linked disaccharide 537 was obtained with complete
stereoselectivity (conservative estimation
a/b >25:1, although no
evidence of the corresponding 1,2-trans anomer could be detected
by 1H NMR) yet only in a modest yield of 65% (Scheme 1). This re-
sult was in line with previously reported results for similar
systems.37
Since our key task was to compare glycosyl thiocyanates with
other classes of thioglycosyl donors, such as thioimidates, we
decided to search for the universal promoters of glycosylation that
would activate both classes of glycosyl donors. If such promoters
were available, one could standardize the reaction conditions
across the spectrum of different classes of glycosyl donors to
obtain comparable results by excluding the possibility of the pro-
moter effect. Based on our previous reports, the most prominent
results for glycosidation of S-benzoxazolyl (SBox, 8)41,55 and
S-thiazolinyl (STaz, 9)44,56 glycosides have been obtained in the
presence of AgOTf as the promoter. Hence, thiocyanate 1 was also
investigated in the presence of stoichiometric amount of AgOTf.
Relatively clean and fast activations (5–15 min) resulted in good
yields for the coupling products 6 and 7 (78–84%, entries 3 and
4). This result could serve as a promising new beginning of com-
parative glycosylation studies with thiocyanates and thioimidates.
However, somewhat lower overall stereoselectivity was observed
in comparison with that seen in TMSOTf-promoted glycosidations
(entries 1 and 2). Nevertheless, the trend remained the same, and
the disaccharide 6 derived from the benzoylated glycosyl acceptor
We assumed that the application of more stable benzoyl or
benzyl protecting groups would enhance the overall stability of
the glycosyl acceptor by reducing the acyl migration. Indeed, the
disaccharide 6,41 derived from benzoylated glycosyl acceptor 3,42
was isolated in a significantly improved yield of 78% and with
complete 1,2-cis stereoselectivity. However, when the structurally
similar benzylated glycosyl acceptor 443 was employed, the corre-
sponding disaccharide 744 was obtained in a yield of 72%, but as a
mixture of diastereomers (a/b = 8.3:1). This notable decrease in the
stereoselectivity of glycosyl thiocyanates, which were previously
described as glycosyl donors capable of the concerted stereospe-
cific displacement, was intriguing. To the best of our knowledge,
this was the first example wherein thiocyanate 1 of the D-gluco
series gave the anomeric mixture, although prior to this study
the stereoselectivity of glycosyl thiocyanates was only investigated
with partially acetylated acceptors.37 Hence, this atypical observa-
tion led us to a decision to reinvestigate glycosidations of thiocya-
nates in a greater detail.
In principle, the effect of protecting groups on the reactivity of
glycosyl acceptor has been noted.16,45–47 It has been observed that
strongly electron-withdrawing ester protecting groups decrease
electron density at the hydroxyl group (or triphenylmethoxy as
in the examples depicted in Scheme 1) thus lowering its nucleophi-
licity and hence reactivity in glycosylation. However, still very lit-
tle is understood about the actual effect that the glycosyl acceptor
protection may have on stereoselectivity of glycosylation.48 Basic
knowledge in this area implies that an enhanced stereocontrol
could be achieved with the less nucleophilic acceptors (such as 2
or 3). Occasionally, a mismatch between donor–acceptor pair
may result in the unexpected stereoselectivity outcome and/or re-
duced yields.49–53 Hence, at first, we attributed the result obtained
for disaccharide 7 to the increased reactivity of the glycosyl accep-
tor 4, which implies that the glycosidation of glycosyl thiocyanate
donors follows unimolecular rather than the earlier proposed con-
certed push-pool mechanism.33,37
In order to extend this finding, we employed common benzoy-
lated (10)42 and benzylated (11)54 6-OH glycosyl acceptors that
were subjected to systematic investigation with the thiocyanate
donor 1 along with a variety of other thio-derivatives. As previ-
ously reported,35 glycosyl thiocyanate 1 could be activated for
reactions with non-tritylated acceptors in the presence of catalytic
amount of TMSOTf. However, these rather sluggish reactions were
commonly accompanied by the competing isomerization of glyco-
syl donor 1 into the corresponding isocyanate, which was reflected
10 was obtained in a notably higher
a-stereoselectivity than its
benzylated counterpart 7 from 11 (7.5:1 and 2.2:1, respectively).
The latter result was particularly surprising considering the sturdy
common knowledge of thiocyanates being among the most stereo-
selective glycosyl donors developed to date. Indeed, this example
clearly illustrated that the effect of glycosyl acceptor and promoter
of glycosylation cannot be underestimated and may have a prevail-
ing effect on the reaction outcome.
When SBox or STaz glycosides (8 and 9, respectively) have been
investigated, a very similar trend has been observed, although
Table 1
Glycosylations of various glycosyl donors 1, 8, and 9 with glycosyl acceptors 10
and 11
OAc
O
AcO
OH
O
OAc
O
AcO
O
PO
AcO
AcO
BnO
PO
R
+
PO
PO
O
OBn
OMe
PO
1: R = SCN
: R = SBox
: R = STaz
10
: P = Bz
11: P = Bn
6
7
: P = Bz
: P = Bn
PO
OMe
8
9
N
O
N
S
Box =
Ta z =
Entry
Donor
Acceptor
Cond’s
Time
Product,
yield (%)
Ratio
a
/ba
OAc
O
1
2
3
4
5
6
7
8
1
1
1
1
8
8
9
9
10
11
10
11
10
11
10
11
A
A
B
B
B
B
B
B
48 h
36 h
6, 45
7, 69
6, 84
7, 78
6, 92
7, 84
6, 89
7, 81
10.2/1
5.0/1
7.5/1
2.2/1
9.5/1
3.8/1
7.4/1
2.7/1
AcO
AcO
5 min
15 min
1 h
30 min
2 h
O
OTr
O
OAc
O
BnO
PO
AcO
AcO
PO
PO
TrC lO 4
O
SCN
+
1,2-DCE
PO
PO
BnO
OMe
PO
OMe
1.5 h
5: P = Ac, 65%, α/β > 25/1
2
1
: P = Ac
Reagents and conditions: All glycosylations were performed in 1,2-dichloroethane
under argon at rt: (A) TMSOTf (0.2 equiv); (B) AgOTf (1.0 equiv for 1, 2.0 equiv for 8
6
7
: P = Bz, 78%, α/β > 25/1
α/β
= 8.3/1
3: P = Bz
4
: P = Bn, 72%,
: P = Bn
and 9), 3 Å molecular sieves.
a
Determined by comparison of integral intensities of the respective signals in 1
H
Scheme 1. Reaction of thiocyanate 1 with differently protected 6-O-trityl glycosyl
acceptors 2–4.
NMR spectra.

2148
S. Kaeothip et al. / Carbohydrate Research 345 (2010) 2146–2150
these activations were slower than those of glycosyl thiocyanate 1,
and required at least 2.0 equiv of AgOTf. Again, disaccharide 6 de-
rived from the benzoylated glycosyl acceptor 10 was obtained with
In conclusion, we observed that protecting groups on glycosyl
acceptor have a profound effect on stereoselectivity of glycosyla-
tion. The effect of protecting groups of glycosyl acceptor on the ste-
reoselectivity of glycosylation seemed very directly correlated to
their electron-withdrawal power. Thus, we demonstrated that
a much higher (approximately threefold)
a-stereoselectivity (en-
tries 5 and 7) than its benzylated counterpart 7 from acceptor 11
(entries 6 and 8). It should be noted that the rate of the reaction
did not clearly correlate with the stereoselectivity observed: for
example, slower glycosidations of the STaz derivative 9 provided
lower stereoselectivity than that of the SBox glycoside 8.
To gain a broader insight, a similar set of experiments has been
performed using a variety of standard secondary glycosyl acceptors
with the uniform benzoyl and benzyl protecting group pattern
(12,57 14,58 16,57 18,59 20,60 and 2261). STaz glycosyl donor 9 was
used in this comparative evaluation. As evident from the results
presented in Table 2, the glycosylations of secondary glycosyl
acceptors were in accordance with the observation made for pri-
mary glycosyl acceptors 10 and 11. Thus, benzoylated glycosyl
acceptors (12, 16 and 20) gave consistently higher stereoselectivity
much higher
a-stereoselectivity can be obtained with glycosyl
acceptors bearing more electron-withdrawing benzoyl substitu-
ents in comparison with that of their benzylated conterparts. This
improvement was consistently achieved with all classes of glycosyl
donors investigated (thiocyanates, thioimidates, and thioglyco-
sides) and was practically independent on the leaving group used.
Both primary and secondary glycosyl acceptors showed the same
trend; and these results were in line with generally accepted prin-
ciples of the effect of protecting groups on glycosyl acceptor. The
actual effect remains unclear, but it is possible that a variety of fac-
tors may have to be considered: dipole moments of the entire mol-
ecule, dipole–dipole interactions, polarizability, donor–acceptor
match-mismatch, the role of the promoter (and the activation
mode), solvent, etc. Further investigation of the protecting and
leaving group effects on stereoselectivity of glycosylation is cur-
rently underway in our laboratory.
(
a
/b ꢀ12:1, entries 1, 3, and 5) for the formation of disaccharides
(13, 17, and 21, respectively) than their benzylated counterparts
(14, 18, and 22) provided for disaccharides 15,44 19, and 2344
b ꢀ6.5–9.3:1, entries 2, 4, and 6).
(a/
Since ethyl thioglycosides are inert in the presence of either
TMSOTf or AgOTf, direct comparison of them with thiocyanates
and thioimidates was not possible. Nevertheless, we supposed that
this general study may benefit from the indirect comparison with a
common ethyl thioglycosides, even though its activation required
entirely different activation protocol. Indeed, a very similar trend
was achieved when ethyl 3,4,6-tri-O-acetyl-2-O-benzyl-1-thio-b-
1. Experimental
1.1. General
Column chromatography was performed on Silica Gel 60 (EM
Science, 70–230 mesh), reactions were monitored by TLC on Kie-
selgel 60 F254 (EM Science). The compounds were detected by
examination under UV light and by charring with 10% sulfuric acid
in methanol. Solvents were removed under reduced pressure at
<40 °C. 1, 2-Dichloroethane was distilled from CaH2 directly prior
to application in glycosylations. Molecular sieves (3 Å or 4 Å), used
for reactions were crushed and activated in vacuo at 390 °C during
8 h in the first instance and then for 2–3 h at 390 °C directly prior
to each application. AgOTf (Acros) was co-evaporated with toluene
(3 ꢁ 10 mL) and dried in vacuo for 2–3 h directly prior to each
application. 1H NMR spectra were recorded in CDCl3 at 300 MHz,
13C NMR spectra were recorded at 75 MHz (Bruker Avance). HRMS
determinations were made with the use of JEOL MStation (JMS-
700) Mass Spectrometer.
D
-glucopyranoside62 was glycosidated in the presence of NIS–TfOH
(or other common promoters for thioglycoside activation).63–66 For
example, disaccharide 6 derived from the benzoylated glycosyl
acceptor 10 was obtained in a significantly higher a-stereoselectiv-
ity than its benzylated counterpart 7 (6.8:1 vs 1.7:1, respectively).
In addition, a very similar trend has been observed with per-ben-
zylated STaz and SEt glycosyl donors (these results are not shown
herein and will be reported elsewhere).
Table 2
The glycosylations of secondary glycosyl acceptors 12, 14, 16, 18, 20, and 22 with the
STaz donor 9
AgOTf
1.2. Typical glycosylation procedures
Glycosyl
Donor
9
Glycosyl Acceptor
12, 14, 16, 18,
20, or 22
Disaccharide
13, 15, 17, 19,
21, or 23
(2 equiv)
+
3Å molec.
sieves
1.2.1. Method A. Typical AgOTf promoted glycosylation
procedure
A mixture of the glycosyl donor (0.11 mmol), glycosyl acceptor
(0.10 mmol), and freshly activated molecular sieves (3 Å, 200 mg)
in (ClCH2)2 (2 mL) was stirred under argon for 1.5 h. Freshly condi-
tioned AgOTf (0.11–0.22 mmol) was added and the reaction mix-
ture was monitored by TLC. Upon completion (see Table), the
reaction mixture was diluted with CH2Cl2 (20 mL), the solid was
filtered off and the residue was washed with CH2Cl2. The combined
filtrate (30 mL) was washed with 20% aq NaHCO3 (15 mL), water
(3 ꢁ 10 mL), and the organic phase was separated, dried over
MgSO4, and concentrated in vacuo. The residue was purified by col-
umn chromatography on silica gel (EtOAc–toluene gradient elu-
tion) to afford the corresponding disaccharide derivative.
Entry
Acceptor
Time (h)
Product, yield (%)
Ratio a/b
1
2
3
4
5
6
12
14
16
18
20
22
16
14
12
8
12
6
13, 89
15, 90
17, 87
19, 85
21, 72
23, 87
11.7/1
6.8/1
12.1/1
6.51
12.01
9.31
OP
O
OP
O
OP
O
RO
PO
PO
RO
PO
PO
PO
PO
RO
OMe
OMe
OMe
12: P=Bz, R=H
16: P=Bz, R=H
20: P=Bz, R=H
13
14
17
18
21
23
: P=Bz, R=Sug
: P=Bn, R=H
: P=Bz, R=Sug
: P=Bn, R=H
: P=Bz, R=Sug
: P=Bn, R=H
1.2.2. Method B. TMSOTf-promoted glycosylation procedure
A mixture of the glycosyl donor (0.11 mmol) and glycosyl
acceptor (0.10 mmol), and freshly activated molecular sieves (4 Å,
200 mg) in (ClCH2)2 (2 mL) was stirred for 1.5 h under argon.
TMSOTf (0.022 mmol) was added and the reaction mixture was
monitored by TLC. Upon completion, the reaction was quenched
15: P=Bn, R=Sug
19: P=Bn, R=Sug
23: P=Bn, R=Sug
OAc
O
AcO
BnO
AcO
Sug =

S. Kaeothip et al. / Carbohydrate Research 345 (2010) 2146–2150
2149
with a drop of pyridine. The reaction mixture was diluted with
CH2Cl2 (20 mL) and washed with 20% aq NaHCO3 (15 mL) and
water (3 ꢁ 10 mL). The organic phase was separated, dried over
MgSO4, and concentrated in vacuo. The residue was purified by col-
umn chromatography on silica gel (EtOAc–toluene gradient elu-
tion) to afford the corresponding disaccharide derivative.
4H, H-6a0, 6b0, CH2Ph), 4.59–4.68 (m, 4H, H-50, CH2Ph), 4.73 (d,
1H, J1,2 = 3.5 Hz, H-1), 4.84 (d, 1H, J2 = 12.0 Hz, 1/2CH2Ph), 4.91
(dd, 1H, J4 ,5 = 10.3 Hz, H-40), 5.49 (dd, 1H, J3 ,4 = 9.8 Hz, H-30),
0
0
0
0
5.60 (d, 1H, J1 ,2 = 3.5 Hz, H-10), 6.90–7.35 (m, 20H, aromatic)
ppm; 13C NMR: d, 20.9, 21.0, 21.1, 55.3, 62.0, 67.3, 68.6, 68.8,
70.0, 72.4, 72.8, 73.5, 73.7 (ꢁ2), 76.4, 77.4, 78.3, 78.9, 97.1, 97.7,
126.6 (ꢁ2), 127.4, 127.8 (ꢁ2), 127.9 (ꢁ2), 128.1 (ꢁ2), 128.5 (ꢁ4),
128.6 (ꢁ4), 128.8 (ꢁ3), 137.7, 137.9, 138.0, 138.6, 170.1, 170.3,
0
0
1.2.3. Method C. NIS-TfOH promoted glycosidation of S-ethyl
glycosides
171.0 ppm; HR-FAB MS: calcd for
907.2789; found: 907.2785.
C
47H48O17Na [M+Na]+:
A mixture of the glycosyl donor (0.11 mmol), glycosyl acceptor
(0.10 mmol), and freshly activated molecular sieves (4 Å, 200 mg)
in (ClCH2)2 (2 mL) was stirred for 1.5 h under argon. NIS
(0.22 mmol) and TfOH (0.022 mmol) were added and the reaction
mixture was monitored by TLC. Upon completion, the reaction
mixture was diluted with CH2Cl2 (20 mL), the solid was filtered
off and the residue was washed with CH2Cl2. The combined filtrate
(30 mL) was washed with 20% aq Na2S2O3 (15 mL) and water
(3 ꢁ 10 mL). The organic phase was separated, dried over MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (EtOAc–toluene gradient elution) to
afford a disaccharide derivative.
1.2.7. Methyl 2-O-(3,4,6-tri-O-acetyl-2-O-benzyl-
glycopyranosyl)-3,4,6-tri-O-benzoyl- -glucopyranoside (21)
Compound 21 was obtained from 9 and 20 in 72% yield (
a/b-D-
a-D
a/
b = 12/1). Analytical data for 21: Rf = 0.40 (EtOAc/toluene, 3/7, v/
v); 1H NMR: d, 1.83 (s, 3H, COCH3), 1.99 (s, 6H, 2 ꢁ COCH3), 3.51
(s, 3H, OCH3), 3.53–3.60 (m, 2H, H-20, 50), 3.87 (dd, 2H,
J6a ,6b = 9.5 Hz, H-6a0, 6b0), 3.94 (dd, 1H, J2,3 = 10.0 Hz, H-2), 4.39
(m, 1H, H-5), 4.46 (dd, 1H, J6a,6b = 12.1 Hz, H-6a), 4.57–4.60 (m,
0
0
2H, H-6b, 1/2CH2Ph), 4.64 (d, 1H, J2 = 12.1 Hz, 1/2CH2Ph), 4.85
0
(dd, 1H, J4 ,5 = 9.6 Hz, H-40), 4.88 (d, 1H, J1 ,2 = 3.5 Hz, H-10), 5.00
0
0
0
(d, 1H, J1,2 = 3.1 Hz, H-1), 5.33 (dd, 1H, J3 ,4 = 9.6 Hz, H-30), 5.54
(dd, 1H, J4,5 = 9.9 Hz, H-4), 6.03 (dd, 1H, J3,4 = 9.7 Hz, H-3), 7.28–
8.06 (m, 20H, aromatic) ppm; 13C NMR: d, 20.7, 20.8, 21.0, 56.0,
61.3, 63.3, 67.8, 68.0, 68.1, 69.8, 71.6, 72.0, 73.4, 77.1, 97.5, 97.6,
128.1 (ꢁ3), 128.4, 128.6 (ꢁ6), 128.8 (ꢁ3), 129.1, 129.7, 129.9
(ꢁ4), 130.1 (ꢁ2), 133.3 (ꢁ2), 133.6, 137.9, 165.6, 165.7, 166.4,
169.9, 170.0, 170.7 ppm; HR-FAB MS: calcd for C47H48O17Na
[M+Na]+: 907.2789; found: 907.2788.
0
0
1.2.4. Methyl 4-O-(3,4,6-tri-O-acetyl-2-O-benzyl-
glycopyranosyl)-2,3,6-tri-O-benzoyl- -glucopyranoside (13)
Compound 13 was obtained from 9 and 12 in 87% yield (
a/b-D-
a-D
a/
b = 12.1:1). Analytical data for 13: Rf = 0.46 (EtOAc–toluene, 3:7,
v/v); 1H NMR: d, 1.97, 2.01, 2.02 (3s, 9H, 3 ꢁ COCH3), 3.37 (dd,
1H, J2 ,3 = 5.8 Hz, H-20), 3.45 (s, 3H, OCH3), 4.09 (m, 1H, H-50),
4.16–4.26 (m, 3H, H-4, 6a0, 6b0), 4.08 (m, 1H, J5,6b = 2.7 Hz, H-5),
4.66 (dd, 1H, H-6a), 4.78 (dd, 1H, J6a,6b = 12.0 Hz, H-6b), 4.85 (dd,
0
0
1H, J4 ,5 = 9.4 Hz, H-40), 5.14 (d, 1H, J1,2 = 2.1 Hz, H-1), 5.14–5.22
0
0
Acknowledgments
(m, 3H, H-10, CH2Ph), 5.36 (dd, 1H, J3 ,4 = 9.8 Hz, H-30), 6.20 (dd,
1H, J3,4 = 8.5 Hz, H-3), 7.03–8.10 (m, 20H, aromatic) ppm; 13C
NMR: d, 20.8 (ꢁ3), 55.7, 62.1, 63.6, 68.5, 68.6, 68.7, 71.7, 72.2,
72.4, 73.1, 75.7, 76.4, 77.4, 97.0, 98.0, 127.8 (ꢁ2), 128.0, 128.5
(ꢁ2), 128.6 (ꢁ3), 128.8 (ꢁ3), 129.2, 129.9 (ꢁ4), 130.1, 130.2
(ꢁ2), 133.3, 133.6 (ꢁ2), 137.7, 165.4, 166.3 (ꢁ2), 169.9, 170.0,
170.7 ppm; HR-FAB MS: calcd for C47H55O14 [M+H]+: 843.3592;
found: 843.3594.
0
0
This work was supported by awards from the NSF (CHE-
0547566) and the American Heart Association (0855743G). Dr. R.
E. K. Winter and Mr. J. Kramer (UM—St. Louis) are thanked for
HRMS determinations.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.08.003.
1.2.5. Methyl 3-O-(3,4,6-tri-O-acetyl-2-O-benzyl-
glycopyranosyl)-2,4,6-tri-O-benzoyl- -glucopyranoside (17)
Compound 17 was obtained from 9 and 16 in 89% yield (
a/b-D-
a-D
a
/
References
b = 11.7:1). Analytical data for 17: Rf = 0.48 (EtOAc–toluene, 3:7,
v/v); 1H NMR: d, 1.76, 1.78, 2.02 (3s, 9H, 3 ꢁ COCH3), 3.27 (dd,
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0
0
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