Benzoylated ethyl 1-thioglycosides: Direct preparation from per-O-benzoylated sugars

Article abstract of DOI:10.1016/j.carres.2012.05.012

d-Glucose, lactose, maltose, and melibiose were benzoylated with Bz ₂O-Et₃N reagent to give fully benzoylated β products. Under the same conditions, d-mannose produced a mixture where the β-benzoate predominated. Treatment of the foregoing compounds with EtSH at slightly elevated temperature (50-60 °C) in the presence of BF ₃·Et₂O as a promoter gave the corresponding ethyl 1-thio glycosides in high yields. The α-products predominated in all cases in the anomeric mixtures formed. Individual products of all reactions were isolated by chromatography, they were obtained in analytically pure state, and were fully characterized by ¹H and ¹³C NMR data and physical constants.

Full text of DOI:10.1016/j.carres.2012.05.012

Carbohydrate Research 357 (2012) 47–52
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Benzoylated ethyl 1-thioglycosides: direct preparation from per-O-benzoylated
sugars
⇑
ˇ
Deepak Sail, Pavol Kovác
NIDDK, LBC, National Institutes of Health, Bethesda, MD 20892-0815, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 April 2012
Received in revised form 14 May 2012
Accepted 15 May 2012
Available online 24 May 2012
D
-Glucose, lactose, maltose, and melibiose were benzoylated with Bz2O–Et3N reagent to give fully ben-
zoylated b products. Under the same conditions, -mannose produced a mixture where the b-benzoate
predominated. Treatment of the foregoing compounds with EtSH at slightly elevated temperature (50–
D
60 °C) in the presence of BF3ꢀEt2O as a promoter gave the corresponding ethyl 1-thio glycosides in high
yields. The a-products predominated in all cases in the anomeric mixtures formed. Individual products
of all reactions were isolated by chromatography, they were obtained in analytically pure state, and were
fully characterized by 1H and 13C NMR data and physical constants.
Published by Elsevier Ltd.
Keywords:
b-Selective 1-O-benzoylation
Thioglycosylation
Thioglycosidation
1. Introduction
of glycosyl acceptors is a well established undesirable side reac-
tion, which often occurs during Lewis acid mediated glycosyla-
Because of their long shelf-life, 1-thioglycosides are very popu-
lar glycosyl donors.1,2 While synthesis of per-O-acetylated 1-thio-
glycosides is fairly simple,3–6 their benzoylated counterparts are
normally prepared indirectly from acetylated thioglycosides, by
sequential deacetylation and benzoylation.7–12 Alternatively, fully
benzoylated thioglycosides were prepared from the corresponding
glycosyl thiocyanates13 or iodides.14 Cao et al.15 prepared ethyl
2,3,4,6-tetra-O-benzoyl-1-thio-b-D-galactopyranoside (13) from
the corresponding penta-O-benzoate by treatment with EtSH in
presence of SnCl4.
Following reports on the use of 1-O-b-acetates of common sug-
ars as glycosyl donors in trifluoromethanesulfonate (TMSOTf)-cata-
lyzed glycosylation,16,17 we have extended the method to the use of
the corresponding 1-O-b-benzoyl derivatives.18 More than a decade
later, Gallo-Rodriguez et al. reported similar approach in their oligo-
saccharide synthesis.19 Here, we describe a similar approach, but to
glycosylation of EtSH, which allows direct preparation of 1-thiogly-
cosides from fully-O-benzoylated saccharides using BF3ꢀEt2O as a
promoter (Scheme 1). To our knowledge, such conversion has not
been described in accessible literature.
tions.16,17,20 For example, formation of as much as ꢁ30% of
methyl 6-O-acetyl-2,3,4-tri-O-benzoyl-b-D-galactopyranoside was
observed when methyl 2,3,4-tri-O-benzoyl-b-
D-galactopyranoside
was glycosylated with 1,2,3,4,6-penta-O-acetyl-b-
D
-galactopyra-
nose in the presence of TMSOTf.18 The significance of 2-O-benzoy-
lated glycosyl donors in glycoside or oligosaccharide synthesis lies
in the fact that the aforementioned transesterification does not
take place when such donors are used.18,21 Also, benzoylated glyco-
syl donors are often stable at base-deficient conditions, which are
required for isomerization of the intermediate orthoesters into gly-
cosides.21 In view of the above, developing a more straightforward
protocol for making benzoylated 1-thio-glycosides than through
the corresponding acetates is desirable.
Knowing that 1,2-trans-O-acetates are normally more reactive
than their 1,2-cis counterparts,1,2 we searched for a simple prepara-
tion of this class of benzoyl derivatives, and have found it in the
work by Luo22 et al. who showed one example of using benzoic
anhydride–triethylamine (Bz2O–Et3N) reagent in stereoselective
1-O-benzoylation. When treated in this way, D-glucose (1), lactose
(14), maltose (18), and melibiose (22) produced virtually only
b-anomers. The product formed from mannose (5) was an anomeric
mixture of per-O-benzoates where the b-compound predominated
(Table 1). There was no advantage to using the Bz2O–Et3N reagent
2. Results and discussion
for benzoylation of
one major of which co-chromatographed with the authen-
tic sample22,23 of 1,2,3,4,6-penta-O-benzoyl-
-galactopyranose
(11).23,24 It has been reported that high proportion of furanoses is
formed during benzoylation of
-galactose at both elevated19 and
sub-ambient25 temperatures. The products were difficult to
D-galactose (10). Several products were formed,
Transfer of the acetyl group during glycosylation reactions
from 2-O-acetylated glycosyl donors to the free hydroxyl group
a
-D
D
⇑
Corresponding author. Tel.: +1 301 496 3569; fax: +1 30 480 5703.
ˇ
E-mail address: kpn@helix.nih.gov (P. Kovác).
0008-6215/$ - see front matter Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.carres.2012.05.012

ˇ
48
D. Sail, P. Kovác / Carbohydrate Research 357 (2012) 47–52
OH
R1
OBz
OBz
R3
R3
EtSH
Bz2
O
O
O
O
BF3.Et2O
DCE
Trie thyl amine
DMF
HO
HO
BzO
BzO
BzO
BzO
R1
R1
OH
R4
R4
R2
R2
R2
3: R1 = H, R2 = SEt, R3 = H, R4 = OBz,
4: R1 = SEt, R2 = H, R3 = H, R4 = OBz,
8: R1 = H, R2 = SEt, R3 = OBz, R4 = H
9: R1 = SEt, R2 = H, R3 = OBz, R4 = H
D
2: R1 = OBz, R2 = H, R3 = H, R4 = OBz,
6: R1 = H, R2 = OBz, R3 = OBz, R4 = H,
7: R1 = OBz, R2 = H, R3 = OBz, R4 = H,
-Glucose (1): R1 = H, R2 = OH
D-Mannose (5): R1 = OH, R2 = H
OBz
BzO
OBz
BzO
BzCl
EtSH
O
O
Pyridine
BF3.Et2
O
D
-Galactose
10
R1
DCE
BzO
BzO
BzO
OBz
BzO
R2
11
12: R1 = H, R2 = SEt
13: R1 = SEt, R2 = H
BzO
BzO
OBz
HO
OBz
OBz
OH
OBz
OH
EtSH
Bz2
O
O
O
O
O
O
O
BF3.Et2O
DCE
Triethyl amine
DMF
R1
OBz
O
O
O
BzO
BzO
HO
HO
BzO
BzO
OH
BzO
BzO
OH
OBz
OBz
OH
R2
15
Lactose
16: R1 = H, R2 = SEt
17: R1 = SEt, R2 = H
14
OH
OBz
O
OBz
O
O
HO
HO
BzO
BzO
BzO
BzO
OH
OBz
OBz
EtSH
Bz2
O
O
O
O
BF3.E t2O
Trie thyl amine
DMF
HO
BzO
BzO
R1
O
O
OBz
O
DCE
HO
BzO
BzO
OH
OH
BzO
BzO
Maltose
18
R2
19
20: R1 = H, R2 = SEt
21: R1 = SEt, R2 = H
HO
HO
BzO
BzO
OH
O
OBz
OBz
O
O
EtSH
BzO
Bz2
O
BzO
BF3.E t2O
Triethyl amine
DMF
HO
BzO
BzO
BzO
BzO
O
O
O
DCE
O
O
O
HO
HO
R1
OBz
BzO
BzO
OH
OH
BzO
BzO
R2
Melibiose
22
23
24: R1 = H, R2 = SEt
25: R1 = SEt, R2 = H
Scheme 1. Benzoylation of
D-glucose,
D-mannose,
D
-galactose, lactose, maltose, and melibiose, and thioglycosidation of their per-O-benzoyl derivatives.
Table 1
Benzoylation of saccharides with benzoic anhydride: product composition and yields
Table 2
Glycosidation of per-O-benzoates with EtSH: combined yields and product
composition
Starting material
Product(s) formed
Combined yield %
a
/b ratioa
Starting material
Products formed
Combined yield %
a/b ratio
2a
2
91
83
b Only
D
-Glucose (1)
2
6
7
11
15
19
23
3, 4
8, 9
8, 9
12, 13
16, 17
20, 21
24, 25
91
93
89
80
76
90
87
6, 7
1/1.5
D-Mannose (5)
8.7a
7.9a
2.7b
1.6b
2.8b
3.8b
Lactose (14)
Maltose (18)
Melibiose (22)
15
19
23
82
74
75
b Only
b Only
b Only
a
Determined after separation by chromatography.
a
Ratio determined after separation by chromatography.
Ratio in the crude product determined by NMR.
b
separate; hence accurate yield of individual compounds formed
could not be determined. As we later discovered during this work,
when thioglycosidation was conducted at elevated temperature
1,2-cis-O-benzoates served our purpose equally well, which agreed
with Xu et al.’s26 similar observation concerning the corresponding
examined (Table 2), with ethyl 1-thio-a-glycosides predominating.
Anomerization of initially formed kinetic products in the presence
of Lewis acid cannot be excluded. Ethyl 1-thio-b-glycosides of
penta-O-acetyl derivatives. Thus,
a-
D
-galactopyranose 1122,23 was
used in the conversion into the corresponding 1-thio-glycosides
D-galactose and melibiose, (13) and (25), respectively, were found
12 and 13.
to co-chromatograph with the starting benzoates. This precluded
monitoring of the progress of the reaction by thin-layer chroma-
tography. In these situations small-scale experiments were con-
ducted in NMR tubes using dichloroethane-d4 as solvent, and the
reaction times required for complete conversion (see Section 3)
Reactions of O-benzoyl derivatives with EtSH in the presence of
BF3ꢀEt2O as a promoter were examined next. The reactions at room
temperature were impractically slow. At moderately elevated
temperature, mixtures of anomers were formed in all cases here

ˇ
D. Sail, P. Kovác / Carbohydrate Research 357 (2012) 47–52
49
of benzoates 11 and 23 were determined by 1H NMR spectroscopy,
by monitoring the disappearance of the low-field signals for H-1 of
the starting materials. All products were fully characterized and
produced NMR spectra consistent with the expected structures.
H-1), 6.05 (t, 1H, J = 9.5 Hz, H-3), 5.90–5.81 (m, 2H, H-2, H-4),
4.66 (dd, 1H, J6a,6b = 12.3, J5,6a = 3.0 Hz, H-6a), 4.52 (dd, 1H,
J5,6b = 4.8 Hz, H-6b), 4.41 (ddd, 1H, J4,5 = 9.9 Hz, H-5); 13C NMR
(150 MHz, CDCl3) d 92.65 (C-1), 73.12 (C-5), 72.76 (C-3), 70.78
(C-2), 68.99 (C-4), 62.62 (C-6); ESI-HRMS calc. for C41H36NO11
[M+NH4]+: 718.2288; Found: 718.2292. Anal. Calcd For
3. Experimental
C41H32O11: C, 70.28; H, 4.60. Found: C, 70.46; H, 4.65.
3.1. General methods
3.3.2. Ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-a- (3) and b-D-
glucopyranoside (4)
Optical rotations were measured at ambient temperature for
solution in CHCl3 with a digital Jasco automatic polarimeter, Model
P-2000. Melting points were measured on a Kofler hot stage. All
reactions were monitored by thin-layer chromatography (TLC) on
Silica Gel 60 coated glass slides. Column chromatography was per-
formed by elution from prepacked columns of silica gel (Varian,
Inc.) with the Isolera Flash Chromatograph (Biotage). Nuclear Mag-
netic Resonance (NMR) spectra were measured at 400 MHz (1H)
and 100 MHz (13C) or at 600 MHz (1H) and 150 MHz (13C) with
Bruker Avance spectrometers. Assignments of NMR signals were
made by homonuclear and heteronuclear 2-dimensional correla-
tion spectroscopy, run with the software supplied with the spec-
trometers. When reporting assignments of NMR signals of
disaccharides, sugar residues are serially numbered, beginning
with the one bearing the aglycon, and are identified by a Roman
numeral superscript in listings of signal assignments. Liquid Chro-
matography–Electron Spray-Ionization Mass Spectrometry (ESI-
MS) was performed with a Waters LCT Premier spectrometer.
Reactions were carried out in closed flasks. Rubber septa used to
close reaction flasks containing organic solvents were protected
with a thin Teflon™ sheet (Laboratory Supplies Co., Inc., Hicksville,
NY), to avoid leaching. Solutions in organic solvents were dried
with anhydrous Na2SO4, and concentrated at 40 °C/2 kPa.
Reaction conditions: EtSH (0.45 mL, 6.0 mmol), BF3ꢀEt2O
(0.554 mL, 4.4 mmol), 1 h, 50 °C; flash chromatography, 30:1?20:1
toluene–EtOAc; yield, starting from 2 (2.80 g, 4.0 mmol), 1.53 g
(60%) of 3 and 0.80 g (31%) of 4.
Compound 3: Rf = 0.7 (15:1 toluene–EtOAc); Mp 137–138 °C
(CH2Cl2–MeOH); [
ene–pet. ether); [a]
a]
+104.2 (c 1.0, CHCl3); lit.7 Mp 135 °C (tolu-
D
D +104 (c 2.0, CHCl3); 1H NMR (600 MHz, CDCl3)
d 6.08 (t, 1H, J = 9.9 Hz, H-3), 5.95 (d, 1H, J1,2 = 5.8 Hz, H-1), 5.68 (t,
1H, J = 9.8 Hz, H-4), 5.51 (dd, 1H, J 2,3 = 10.2 Hz, H-2), 4.88 (ddd, 1H,
J4,5 = 10.1, J5,6b = 5.4, J5,6a = 2.8 Hz, H-5), 4.60 (dd, 1H,
J6a,6b = 12.2 Hz, H-6a), 4.52 (dd, 1H, J5,6b = 5.5 Hz, H-6b), 2.70–
2.55 (m, 2H, CH2), 1.25 (t, 3H, J = 7.4 Hz, CH3); 13C NMR
(150 MHz, CDCl3) d 81.98 (C-1), 71.63 (C-2), 70.87 (C-3), 69.49
(C-4), 68.08 (C-5), 63.02 (C-6), 24.24 (CH2), 14.61 (CH3); ESI-HRMS
calcd for C36H36NO9S [M+NH4]+: 658.2111; found: 658.2123; Anal.
Calcd for C36H32O9S: C, 67.49; H, 5.03. Found: C, 67.71; H, 5.03.
Compound 4: The solid obtained after freeze-drying of a solu-
tion in benzene could not be crystallized. Rf = 0.6 (15:1 toluene–
EtOAc); [
leum ether); [
a
]
D +29.1 (c 1.0, CHCl3); lit.7 Mp 108–109 °C (ether–petro-
a
]
D
+27 (c 1.8, CHCl3); 1H NMR (600 MHz, CDCl3): d
5.93 (t, 1H, J = 9.5 Hz, H-3), 5.67 (t, 1H, J = 9.8 Hz, H-4), 5.57 (t,
1H, J = 9.7 Hz, H-2), 4.87 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.63 (dd, 1H,
J6a,6b = 12.2, J5,6a = 3.1 Hz, H-6a), 4.50 (dd, 1H, J5,6b = 5.5 Hz, H-6b),
4.18 (ddd, 1H, J4,5 = 10.0 Hz, H-5), 2.84–2.69 (m, 2H, SCH2CH3),
1.26 (t, 3H, J = 7.4 Hz, SCH2CH3); 13C NMR (150 MHz, CDCl3): d
83.90 (C-1), 76.25 (C-5), 74.05 (C-3), 70.54 (C-2), 69.57 (C-4),
63.30 (C-6), 24.38 (SCH2CH3), 14.90 (SCH2CH3); ESI-HRMS calcd
for C36H36NO9S [M+NH4]+: 658.2111; found: 658.2114. Anal. Calcd
for C36H32O9S: C, 67.49; H, 5.03. Found: C, 67.56; H, 5.01.
3.2. General procedures for benzoylation
The free sugar (2–5 mmol) was dissolved in DMF (10 mL/
mmol), Et3N (4 equiv/OH) was added followed by addition of
Bz2O (2 equiv/OH), and the mixture was stirred at conditions spec-
ified below. When the conversion was complete (TLC), excess of
MeOH was added and the mixture was stirred overnight at room
temperature. After concentration, a solution of the residue in
CH2Cl2 was washed with saturated solution of sodium bicarbonate.
The organic phase was dried, concentrated, and the crude mixture
was chromatographed, to give pure substances and, occasionally,
mixed fractions. For combined yields, see Table 1.
3.3.3. 1,2,3,4,6-Penta-O-benzoyl-a- (6) and b-D-mannopyranose
(7)
Compound 5: Reaction conditions: 40 h, rt; flash chromatogra-
phy, 50:1?30:1 toluene–EtOAc; yield, starting from 5 (0.180 g,
1.0 mmol), 0.234 g (33%) of 6 and 0.342 g (50%) of 7.
Compound 6: Rf = 0.5 (19:1 toluene–EtOAc); Mp 150.5–152 °C
(MeOH); [
a
]
ꢂ20.2 (c 1.0, CHCl3); lit.27 Mp 152–153 °C; [
a]
D
D
3.3. General procedure for thioglycosidation
ꢂ18.6 (c 1.6, CHCl3); 1H NMR (400 MHz, CDCl3): d 6.63 (d, 1H,
J1,2 = 2.0 Hz, H-1), 6.28 (t, 1H, J = 10.2 Hz, H-4), 6.07 (dd, 1H,
J3,4 = 10.2, J2,3 = 3.3 Hz, H-3), 5.91 (dd, 1H, H-2), 4.70 (dd, 1H,
J6a,6b = 12.2, J5,6a = 2.5 Hz, H-6a), 4.57 (dt, 1H, J4,5 = 10.0 Hz, H-5),
4.50 (dd, 1H, J5,6b = 3.7 Hz, H-6b); 13C NMR (100 MHz, CDCl3) d
91.37 (C-1, JC-1,H-1 = 178.8 Hz), 71.18 (C-5), 69.99 (C-3), 69.43 (C-
2), 66.18 (C-4), 62.34 (C-6); ESI-HRMS calcd for C41H36NO11
BF3ꢀEt2O was added to a solution of EtSH and sugar per-O-ben-
zoate in 1,2-dichloroethane, and the mixture was stirred until all
starting material was consumed (TLC). For amounts of solvent, re-
agents, and reaction conditions, see individual preparations (be-
low). Et3N (excess of over the molar amount of BF3ꢀEt2O) was
added, the mixture was concentrated, and a solution of the residue
in CH2Cl2 was washed with saturated solution of sodium bicarbon-
ate. After concentration of the organic phase, chromatography of
the material in the residue gave pure substances or mixtures of
anomers. For combined yields, see Table 2.
[M+NH4]+: 718.2288; found: 718.2274. Anal. Calcd for C41H32O11
C, 70.28; H, 4.60. Found: C, 70.56; H, 4.80.
:
Compound 7: Rf = 0.4 (19:1 toluene–EtOAc); Mp 160–161.5 °C
(MeOH); [
a
]
ꢂ84.2 (c 1.0, CHCl3); lit.28 Mp 161–161.5 °C (EtOH);
D
[a
]
D
ꢂ80.7 (CHCl3); 1H NMR (600 MHz, CDCl3) d 6.44 (d, 1H,
J1,2 = 1.2 Hz, H-1), 6.18 (t, 1H, J = 9.8 Hz, H-4), 6.11 (dd, 1H,
J2,3 = 3.2 Hz, H-2), 5.81 (dd, 1H, J3,4 = 9.9 Hz, H-3), 4.76 (dd, 1H,
J6a,6b = 12.3, J5,6a = 2.8 Hz, H-6a), 4.56 (dd, 1H, J5,6b = 4.3 Hz, H-6b),
4.38 (ddd, 1H, J4.5 = 9.7 Hz, H-5); 13C NMR (150 MHz, CDCl3) d
91.19 (C-1, JC-1,H-1 = 163.3 Hz), 73.28 (C-5), 71.51 (C-3), 69.36 (C-
2), 69.32 (C-4), 62.61 (C-6); ESI-HRMS calcd for C41H36NO11
3.3.1. 1,2,3,4,6-Penta-O-benzoyl-b-D-glucopyranose (2)
Reaction conditions: 16 h, rt; flash chromatography, 4:1 hex-
ane–acetone; yield, starting from 1 (0.9 g, 5.0 mmol), 3.2 g (91%);
Rf = 0.3 (4:1 hexane–acetone); Mp 182–185 °C (MeOH);
+24.4 (c 1.0, CHCl3); lit.27 Mp 189–192 °C (AcOH); [
+24.2 (c
2.6, CHCl3); 1H NMR (600 MHz, CDCl3): d 6.30 (d, 1H, J1,2 = 8.1 Hz,
[a]
D
a
]
D

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D. Sail, P. Kovác / Carbohydrate Research 357 (2012) 47–52
50
[M+NH4]+: 718.2288; found: 718.2292. Anal. Calcd for C41H32O11
C, 70.28; H, 4.60. Found: C, 70.49; H, 4.69.
:
658.2111; found: 658.2111; Anal. Calcd for C36H32O9S: C, 67.49;
H, 5.03. Found: C, 67.39; H, 5.00.
Compound 13; Amorphous solid after freeze-drying of a solu-
3.3.4. Ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-
mannopyranoside (9)
a- (8) and b-
D
-
tion in benzene; Rf = 0.3 (3:1 hexane–acetone); [
a] +98.4 (c 1.0,
D
CHCl3); lit.30 +106 (c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3)
[a]
D
Reaction conditions: EtSH (1.5 mL, 2.0 mmol), BF3ꢀEt2O (0.23 mL,
1.8 mmol), 3 h (starting from 6), 5 h (starting from 7), 50 °C; flash
chromatography, 50:1?25:1 toluene–EtOAc.
Compound 8: yield, starting from 6 (0.700 g, 1 mmol), 0.536 g
(84%), starting from 7 (0.700 g, 1 mmol), 0.504 g (79%); Rf = 0.7
d: 6.04 (br d, 1H, H-4), 5.84 (t, 1H, J = 9.9 Hz, H-2), 5.65 (dd, 1H,
J2,3 = 9.9, J3,4 = 3.5 Hz, H-3), 4.88 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.67
(dd, 1H, J6a,6b = 11.2, J5,6a = 6.5 Hz, H-6a), 4.41 (dd, 1H,
J5,6b = 6.5 Hz, H-6b), 4.36 (t, 1H, J = 6.6 Hz, H-5), 2.95–2.72 (m,
2H, SCH2CH3), 1.32 (t, 3H, SCH2SCH3); 13C NMR (150 MHz, CDCl3)
d: 84.31 (JC-1,H-1 = 152.5 Hz, C-1), 75.03 (C-5), 72.70 (C-3), 68.36
(C-4), 68.19 (C-2), 62.60 (C-6), 24.53 (SCH2CH3), 14.98 (SCH2CH3);
(15:1 toluene–EtOAc); Mp 120–121.5 °C (EtOH); [
a
]
ꢂ14.0 (c
D
1.0, CHCl3); lit.29: Mp 124–125 °C (EtOH); [
a]
D ꢂ15.8 (c 0.8, CHCl3).
1H NMR (600 MHz, CDCl3) d 6.17 (t, 1H, J = 10.0 Hz, H-4), 5.89 (dd,
1H, J3,4 = 9.9, J2,3 = 3.2 Hz, H-3), 5.87 (dd, 1H, J1,2 = 1.3 Hz, H-2), 5.59
(br d, 1H, H-1), 4.85 (ddd, 1H, J4,5 = 10.1, J5,6b = 4.5, J5,6a = 2.6 Hz, H-
5), 4.69 (dd, 1H, J6a,6b = 12.2 Hz, H-6a), 4.54 (dd, 1H, H-6b), 2.95–
2.58 (m, 2H, SCH2CH3), 1.35 (t, 3H, SCH2CH3); 13C NMR
(150 MHz, CDCl3) d 82.29 (C-1, JC-1,H-1 = 168.3 Hz), 72.08 (C-2),
70.48 (C-3), 69.19 (C-5), 66.99 (C-4), 62.82 (C-6), 25.57 (SCH2CH3),
14.81 (SCH2CH3); ESI-HRMS calcd for C36H36NO9S [M+NH4]+:
658.2111; found: 658.2126. Anal. Calcd for C36H32O9S: C, 67.49;
H, 5.03. Found: C, 67.70; H, 5.09.
ESI-HRMS calcd for C
36H36NO9S [M+NH4]+: 658.2111; found:
658.2111; Anal. Calcd for C36H32O9S: C, 67.49; H, 5.03. Found: C,
67.73; H, 5.02.
3.3.7. 1,2,3,6-Tetra-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-b-D-
galactopyranosyl)-b-D-glucopyranose (Octa-O-benzoyl-b-
lactose, 15)
Reaction conditions: 40 h, 50 °C; flash chromatography, 30:1?
20:1 toluene–EtOAc; yield, starting from lactose monohydrate
(1.44 g, 4.0 mmol), 3.85 g (82%); Rf = 0.5 (10:1 toluene–EtOAc);
Compound 9: Amorphous solid after freeze-drying of a solution
in benzene; yield, starting from 6 (0.700 g, 1 mmol), 0.062 g (10%);
yield, starting from 7 (0.700 g, 1 mmol), 0.061 g (10%); Rf = 0.5
[
a D
]
]
+45.7 (c 1.0, CHCl3); lit.31 Mp 140–142 °C (acetone–MeOH);
+38.1 (c 0.9, CHCl3); 1H NMR (600 MHz, CDCl3) d 6.15 (d, 1H,
[a D
J1,2 = 8.1 Hz, H-10), 5.96 (t, 1H, J = 9.3 Hz, H-3), 5.80 (dd, 1H,
J2,3 = 9.6 Hz, H-2), 5.78–5.72 (m, 2H, H-20,40), 5.39 (dd, 1H,
(15:1 toluene–EtOAc);
[a
]
D
ꢂ150.4 (c 1.0, CHCl3); 1H NMR
J2 ,3 = 10.4, J3 ,4 = 3.4 Hz, H-30), 4.90 (d, 1H, J1 ,2 = 7.9 Hz, H-10), 4.60
(dd, 1H, J6a,6b = 12.4, J5,6a = 1.9 Hz, H-6a), 4.54 (dd, 1H,
J5,6b = 3.9 Hz, H-6b), 4.41 (t, 1H, J = 9.4 Hz, H-4), 4.08 (ddd, 1H,
J4,5 = 9.9 Hz, H-5), 3.90 (t, 1H, J = 6.8 Hz, H-50), 3.78 (dd, 1H,
0
0
0
0
0
0
(600 MHz, CDCl3) d 6.02 (dd, 1H, J2,3 = 3.3, J1,2 = 0.9 Hz, H-2), 6.00
(t, 1H, J = 10.0 Hz, H-4), 5.67 (dd, 1H, J3,4= 10.1 Hz, H-3), 5.11 (br
d, 1H, H-1), 4.71 (dd, 1H, J6a,6b = 12.1, J5,6a = 2.9 Hz, H-6a), 4.54
(dd, 1H, J5,6b = 5.4 Hz, H-6b), 4.20–4.18 (m, 1H, H-5), 2.83–2.74
(m, 2H, SCH2CH3), 1.31 (t, 3H, J = 7.4 Hz, SCH2CH3); 13C NMR
(150 MHz, CDCl3) d 82.84 (C-1, JC-1,H-1 = 152.2 Hz), 76.53 (C-5),
72.77 (C-3), 71.35 (C-2), 66.85 (C-4), 63.43 (C-6), 25.86 (SCH2CH3),
14.97 (SCH2CH3); ESI-HRMS calcd for C36H36NO9S [M+NH4]+:
658.2111; found: 658.2119; Anal. Calcd for C36H32O9S: C, 67.49;
H, 5.03. Found: C, 67.19; H, 4.99.
J6a ,6b = 11.3, J5 ,6a = 6.4 Hz, H-6a0), 3.71 (dd, 1H, J5 ,6b = 7.1 Hz, H-
0
0
0
0
0
0
13
6b0); C NMR (150 MHz, CDCl3) d 101.00 (C-10), 92.53 (C-1), 75.48
(C-4), 73.75 (C-5), 72.76 (C-3), 71.69 (C-30), 71.32 (C-50), 70.61 (C-
2), 69.73, 67.39 (C-20,40), 62.04 (C-6), 60.92 (C-60); ESI-HRMS calcd
for C68H58NO19 [M+NH4]+: 1192.3603; found: 1192.3623; Anal.
Calcd for C68H54O19: C, 69.50; H, 4.63. Found: C, 69.53; H, 4.61.
3.3.5. 1,2,3,4,6-Penta-O-benzoyl-
This compound was prepared as described.24 Mp 161.5–162.5 °C
(EtOH); [a D
+193.9 (c 1.0, CHCl3); lit.24 Mp 158–159 °C (MeOH);
D +187.0 (c 4.0, CHCl3); 1H NMR (600 MHz, CDCl3) d: 6.96 (d, 1H,
J1,2 = 3.7 Hz, H-1), 6.20 (br d, 1H, H-4), 6.13 (dd, 1H, J2,3 = 10.7,
J3,4 = 3.4 Hz, H-3), 6.03 (dd, 1H, H-2), 4.84 (t, 1H, J = 6.8 Hz, H-5),
4.64 (dd, 1H, J6a,6b = 11.4, J5,6a = 6.4 Hz, H-6a), 4.43 (dd, 1H,
J5,6b = 6.9 Hz, H-6b); 13C NMR (150 MHz, CDCl3): d 90.65 (C-1), 69.41
(C-5), 68.50 (C-3), 68.43 (C-4), 67.66 (C-2), 61.80 (C-6). ESI-HRMS
calcd for C41H36NO11 [M+NH4]+: 718.2288; found: 718.2258; Anal.
Calcd for C41H32O11: C, 70.28; H, 4.60. Found: 70.14; H, 4.70.
a
-
D
-galactopyranose (11)
3.3.8. Ethyl 2,3,6-tri-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-b-
D
-galactopyranosyl)-1-thio-
a
- (16) and b-
D-glucopyranoside
]
(17) (Hepta-O-benzoyl-1-thio-
a
- and b-lactoside)
[a]
Reaction conditions: EtSH (0.15 mL, 2.0 mmol), BF3ꢀEt2O
(0.23 mL, 1.8 mmol), 2 h, 50 °C; chromatography, 50:1?25:1 tolu-
ene–EtOAc; yield, starting from 15 (1.175 g, 1.0 mmol), 1.024 g
(76%) of mixture of 16 and 17. Compound 16 crystallized from
DCM–MeOH.
Compound 16: Rf = 0.5 (19:1 toluene–EtOAc); Mp 221–222.5 °C
(CH2Cl2–MeOH); [
a]
D
+91.3 (c 1.0, CHCl3); 1H NMR (600 MHz,
CDCl3) d 5.95 (t, 1H, J = 9.6 Hz, H-3), 5.82 (d, 1H, J1,2 = 5.9 Hz, H-
1), 5.75 (br d, partially overlapped, H-40), 5.73 (dd, partially over-
0
0
0
0
3.3.6. Ethyl 2,3,4,6-tetra-O-benzoyl-1-thio-
galactopyranoside (13)
a
- (12) and b-
D
-
lapped, J2 ,3 = 10.2, J1 ,2 = 8.0 Hz), 5.43 (dd, 1H, J2,3 = 10.2 Hz, H-2),
5.38 (dd, 1H, J3 ,4 = 3.4 Hz, H-30), 4.92 (d, 1H, H-10), 4.61– 4.52
0
0
Reaction conditions: EtSH (0.375 mL, 5.0 mmol), BF3ꢀEt2O
(0.504 mL, 4.0 mmol), 16 h (optimum time determined by NMR
spectroscopy), 60 °C; flash chromatography, 5:1 hexane–acetone;
yield, starting from 11 (1.40 g, 2.0 mmol), 0.422 g of pure 12
(33%), 0.317 g of pure 13 (25%). Unresolved mixture of 12 and 13
(0.282 g, 22%) was also obtained.
(m, 3H, H-5, H-6a0, H-6b0), 4.21 (t, 1H, J = 9.5 Hz, H-4), 3.91 (t, 1H,
J = 6.7 Hz, H-50), 3.85 (d, 1H, J6a ,6b = 11.3, J5 ,6a = 6.4 Hz, H-6a0),
0
0
0
0
3.76 (dd, 1H, J5 ,6b = 7.1 Hz, H-6b0), 2.61–2.45 (m, 2H, SCH2CH3),
0
0
1.18 (t, J = 7.4 Hz, 3H, SCH2CH3); 13C NMR (150 MHz, CDCl3) d
101.13 (JC-1 ,H-1 = 160.1 Hz, C-10), 81.91 (JC-1,H-1 = 168.2 Hz, C-1),
76.35 (C-4), 71.95 (C-30), 71.49 (C-2), 71.30 (C-50), 70.87 (C-3),
69.88 (C-20), 68.78 (C-5), 67.45 (C-40), 62.53 (C-6), 61.05 (C-60),
24.23 (SCH2CH3), 14.55 (SCH2CH3); ESI-HRMS calcd for C63H58
NO17S [M+NH4]+: 1132.3425; found: 1132.3457; Anal. Calcd for
0
0
Compound 12: Amorphous solid after freeze-drying of a solu-
tion in benzene; Rf = 0.4 (3:1 hexane–acetone); [a] +166.6 (c 1.0,
D
CHCl3); 1H NMR (600 MHz, CDCl3) d 6.09–5.99 (m, 2H, H-1, H-4),
5.92–5.82 (m, 2H, H-2, H-3), 5.03 (dd, 1H, J5,6a = 7.0, J5,6b = 5.6 Hz,
H-5), 4.62 (dd, 1H, J6a,6b = 11.5 Hz, H-6a), 4.44 (dd, 1H, H-6b),
2.74–2.49 (m, 2H, SCH2CH3), 1.25 (m, 3H, SCH2CH3); 13C NMR
(150 MHz, CDCl3) d 81.22 (JC-1,H-1 = 168.5 Hz, C-1), 68.05, 67.96,
67.90 (C-2, C-3, C-4), 66.22 (C-5), 61.60 (C-6), 23.03 (SCH2CH3),
13.57 (SCH2CH3); ESI-HRMS calcd for C36H36NO9S [M+NH4]+:
C
63H54O17S: C, 67.85; H, 4.88. Found: C, 67.94; H, 4.90.
The mother liquor contained predominantly ethyl 2,3,6-tri-
O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-b-
hio-b- -glucopyranoside 17, and a solvent suitable for separation by
chromatography could not be found; Rf = 0.5 (19:1 toluene–EtOAc);
amorphoussolid;lit.30 amorphoussolid;1HNMR(600 MHz, CDCl3)d
D-galactopyranosyl)-1-t
D

ˇ
D. Sail, P. Kovác / Carbohydrate Research 357 (2012) 47–52
51
5.82 (t, 1H, J = 9.3 Hz, H-3), 5.73 (m, partially overlapped, H-40), 5.72
J = 9.2 Hz, H-3), 5.74 (d, 1H, J1 ,2 = 3.9 Hz, H-10), 5.65 (t, 1H,
J = 9.8 Hz, H-40), 5.36 (t, 1H, J = 9.6 Hz, H-2), 5.24 (dd, 1H, H-20),
4.93 (dd, 1H, J6a,6b = 12.1, J5,6a = 2.4 Hz, H-6a), 4.81 (d, 1H,
J1,2 = 9.8 Hz, H-1), 4.74 (dd, 1H, J5,6b = 4.4 Hz, H-6b), 4.49 (t, 1H,
0
0
(dd, partially overlapped, J2 ,3 = 10.3, J1 2 = 7.9 Hz, H-20), 5.50 (t, 1H,
0
0
0
0
J = 9.7 Hz, H-2), 5.37 (dd, 1H, J3 ,4 = 3.4 Hz, H-30), 4.87 (d, 1H, H-10),
4.73 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.60 (dd, 1H, J6a,6b = 12.2,
J5,6a = 1.8 Hz, H-6a), 4.49 (dd, 1H, J5,6b = 4.7 Hz, H-6b), 4.24 (t, 1H,
J = 9.5 Hz, H-4), 3.90 (t, 1H, J = 6.8 Hz, H-50), 3.86 (ddd, 1H,
J4,5 = 10.0 Hz, H-5), 3.72 (m, 2H, H-6a0, H-6b0), 2.75–2.61 (m, 2H,
SCH2CH3), 1.20 (t, J = 7.5 Hz, 3H, SCH2CH3); 13C NMR (150 MHz,
0
0
0
0
J = 9.3 Hz, H-4), 4.45 (dt, partially overlapped, J4 ,5 = 10.1,
J5 ,6a ,b = 3.5 Hz, H-50), 4.40 (dd, 1H, J6a ,6b = 12.2 Hz, J5 ,6a = 3.1 Hz,
0
0
0
0
0
0
0
H-6a0), 4.26 (dd, 1H, J5 ,6b = 3.8 Hz, H-6b0), 4.10 (ddd, 1H,
J4,5 = 9.6 Hz, H-5), 2.86–2.58 (m, 2H, SCH2CH3), 1.22 (t, 3H,
0
0
CDCl3) d 100.92 (JC-1 ,H-1 = 161.4 Hz, C-10), 83.74 (JC-1,H-1 = 153.5 Hz,
C-1), 77.00 (C-5), 75.92 (C-4), 73.97 (C-3), 71.75 (C-30), 71.31 (C-
50), 70.48 (C-2), 69.82 (C-20), 67.44 (C-40), 62.65 (C-6), 60.98 (C-60),
J = 7.5 Hz, SCH2CH3); 13C NMR (150 MHz, CDCl3) d 96.3 (JC-1 ,H-1
=
0
0
0
0
175.7 Hz, C-10), 83.5 (JC-1,H-1 = 154.7 Hz, C-1), 76.76 (C-5), 76.11
(C-3), 73.03 (C-4), 70.98 (C-2), 70.87 (C-20), 69.81 (C-30), 69.12
(C-50), 69.04 (C-40), 63.62 (C-6), 62.48 (C-60), 24.3 (SCH2CH3), 14.9
24.43 (SCH2CH3), 14.85 (SCH2CH3); ESI-HRMS calcd for C63H58NO17
S
[M+NH4]+: 1132.3425; found: 1132.3441; Anal. Calcd for C63H54
O17S: C, 67.85; H, 4.88. Found: C, 67.82; H, 4.80.
(SCH2CH3); ESI-HRMS calcd for C63H58NO17
1132.3425; found: 1132.3401; Anal. Calcd for C63H54O17S: C,
67.85; H, 4.88. Found: C, 67.93; H, 4.76.
S
[M+NH4]+:
3.3.9. 1,2,3,6-tetra-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-a-D-
glucopyranosyl)-b-
D-glucopyranose (Octa-O-benzoyl-b-maltose,
3.3.11. 1,2,3,4-tetra-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-
-galactopyranosyl)-b- -glucopyranose (Octa-O-benzoyl-b-
melibiose, 23)
a-
19)
D
D
Reaction conditions: 40 h, 50 °C; flash chromatography,
50:1?25:1 toluene–EtOAc; yield, starting from 18 (1.71 g,
5.0 mmol), 4.32 g (74%); Rf = 0.5 (15:1 toluene–EtOAc); Mp 193–
Reaction conditions: 16 h, 50 °C; flash chromatography,
50:1?20:1 toluene–EtOAc; yield, starting from melibiose mono-
hydrate (1.08 g, 3.0 mmol), 2.53 g (75%); Rf = 0.5 (15:1 toluene–
195 °C (MeOH); [
(acetone–MeOH); [
a
]
a
+62.0 (c 1.0, CHCl3); lit.32 Mp 190–192 °C
D
D
]
+68.2 (c 1.0, CHCl3); 1H NMR (600 MHz,
EtOAc); Mp 165–168 °C (MeOH); [a]
+141.3 (c 1.0, CHCl3); lit.34
D
CDCl3) d 6.27 (d, 1H, J1,2 = 7.4 Hz, H-1), 6.11 (t, 1H, J = 10.0 Hz, H-
(anomeric configuration not specified; in the absence of NMR data,
judging by physical constants, the compound reported previously
30), 5.85 (t, 1H, J = 8.6 Hz, H-3), 5.79 (d, 1H, J1 2 = 3.9 Hz, H-10),
5.68 (t, 1H, J = 9.8 Hz, H-40), 5.64 (dd, 1H, J2,3 = 8.7 Hz, H-2), 5.26
0
0
is likely the
a anomer): Mp 111–112 °C (EtOH), [a] +174 (c 4.55,
D
(dd, 1H, J2 ,3 = 10.5 Hz, H-20), 4.90 (dd, 1H, J6a,6b = 12.3,
J5,6a = 2.5 Hz, H-6a), 4.78 (dd, 1H, J5,6b = 3.8 Hz, H-6b), 4.67 (t, 1H,
CHCl3); 1H NMR (600 MHz, CDCl3) d 6.15 (d, 1H, J1,2 = 8.2 Hz, H-
0
0
1), 6.12 (dd, 1H, J2 ,3 = 10.7, J3 ,4 = 3.5 Hz, H-30), 6.02–5.99 (m, par-
0
0
0
0
J = 9.0 Hz, H-4), 4.44 (dt, 1H, J4 ,5 = 10.1 Hz, H-50), 4.41 – 4.35 (m,
tially overlapped, H-40), 5.98 (t, partially overlapped, J 9.7 Hz, H-3),
0
0
2H, H-6a0, H-5), 4.21 (dd, 1H, J6a ,6b = 12.3, J5 ,6b = 3.5 Hz, H-6b0);
13C NMR (150 MHz, CDCl3) d 96.37 (C-10), 92.13 (C-1), 74.81 (C-
3), 73.47 (C-5), 72.60 (C-4), 71.09 (C-2), 70.91 (C-20), 69.80 (C-30),
69.14 (C-50), 68.94 (C-40), 63.09 (C-6), 62.34 (C-60); ESI-HRMS calcd
for C68H58NO19 [M+NH4]+: 1192.3603; found: 1192.3596; Anal.
Calcd for C68H54O19: C, 69.50; H, 4.63. Found: C, 69.39; H, 4.80.
5.71 (dd, 1H, J1 ,2 = 3.7 Hz, H-20), 5.70 (t, 1 H, J = 9.8 Hz, H-4), 5.61
(dd, 1H, J2,3 = 9.8 Hz, H-2), 5.43 (d, 1H, H-10), 4.65 (br t, 1H, H-50),
0
0
0
0
0
0
4.36 (dd, 1H, J6a ,6b = 11.5, J5 ,6a = 7.7 Hz, H-60a0), 4.23 (ddd, 1H,
0
0
0
0
0
0
J4,5 = 10.1, J5,6a = 5.1, J5,6b = 1.8 Hz, H-5), 4.09 (dd, 1H, J5 ,6b = 4.9 Hz,
H-6b0), 4.02 (dd, 1H, J6a,6b = 11.4 Hz, H-6a), 3.83 (dd, 1H, H-6b); 13
C
NMR (150 MHz, CDCl3) d 96.57 (C-10), 92.92 (C-1), 74.20 (C-5),
72.87 (C-3), 70.85 (C-2), 69.35 (C-40), 68.89 (C-20), 68.59 (C-4),
68.55 (C-30), 67.14 (C-50), 65.68 (C-6), 62.86 (C-60); ESI-HRMS calcd
for C68H58NO19 [M+NH4]+: 1192.3603; found: 1192.3628; Anal.
Calcd for C68H54O19: C, 69.50; H, 4.63. Found: C, 69.23; H, 4.89.
3.3.10. Ethyl 2,3,6-tri-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-
-glucopyranosyl)-1-thio- - (20) and b- -glucopyranoside (21)
(Ethyl hepta-O-benzoyl-1-thio- - and b-maltoside)
a-
D
a
D
a
Reaction conditions: EtSH (0.34 mL, 4.5 mmol), BF3ꢀEt2O
(0.42 mL, 3.3 mmol), 3 h, 50 °C; chromatography, 50:1 toluene–
EtOAc; yield, starting from 19 (3.525 g, 3.0 mmol), 3.02 g (90%) of
mixture of 20 and 21. Only small amounts of pure 20 and 21 could
be isolated by flash chromatography.
3.3.12. Ethyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-
-galactopyranosyl)-1-thio- - (24) and b- -glucopyranoside
(25) (Ethyl hepta-O-benzoyl-1-thio- - and b-melibioside)
Reaction conditions: EtSH (0.19 mL, 2.5 mmol), BF3ꢀEt2O
(0.25 mL, 2.0 mmol), 16 h, 60 °C (optimum reaction time deter-
mined by NMR spectroscopy); chromatography, 50:1?30:1 tolu-
ene–EtOAc; yield, starting from 23 (1.175 g, 1.0 mmol), 0.320 g
(29%) of 24, 0.159 g (14%) of 25. Unresolved mixture of 24 and
25 (0.495 g, 44%) was also obtained.
a-
D
a
D
a
Compound 20: Amorphous solid after freeze-drying of a solu-
tion in benzene; Rf = 0.5 (19:1 toluene–EtOAc); [
a] +112.2 (c 1.0,
D
CHCl3); 1H NMR (600 MHz, CDCl3) d 6.11 (dd, 1H, J2 ,3 = 10.5,
0
0
J3 ,4 = 9.6 Hz, H-30), 5.96 (dd, 1H, J2,3 = 10.0, J3,4= 8.9 Hz, H-3), 5.82
0
0
(d, 1H, J1,2 = 5.6 Hz, H-1), 5.77 (d, 1H, J1 ,2 = 3.9 Hz, H-10), 5.68 (t,
1H, J = 9.8 Hz, H-40), 5.29 (dd, partially overlapped, H-20), 5.28
(dd, partially overlapped, H-2), 4.87 (dd, 1H, J6a,6b = 11.9,
J5,6a = 2.1 Hz, H-6a), 4.83–4.80 (m, 1H, H-5), 4.78 (dd, 1H,
0
0
Compound 24: Amorphous solid after freeze-drying of a solu-
tion in benzene; Rf = 0.6 (12:1 toluene–EtOAc); [
a] +165.0 (c 1.0,
D
CHCl3); 1H NMR (600 MHz, CDCl3) d 6.05 (br d, 1H, J3 ,4 = 3.4 Hz,
0
0
H-40), 6.01 (dd, J2 ,3 = 10.5, Hz, H-30), 5.98 (t, 1H, J = 9.9 Hz, H-3),
0
0
0
0
0
0
0
J5,6b = 4.5 Hz, H-6b), 4.50 (dt, 1H, J4 ,5 = 10.1, J5 ,6a ,b = 3.4 Hz, H-
5.81 (d, 1H, J1,2 = 5.9 Hz, H-1), 5.71 (dd, 1H, J1 ,2 = 3.7 Hz, H-20),
5.48 (d, 1H, H-10), 5.35 (t, 1H, J = 9.9 Hz, H-4), 5.05 (dd, 1H,
J2,3 = 10.1 Hz, H-2), 4.72 (br dd, 1H, H-50), 4.69 (ddd, 1H,
50), 4.45 (dd, 1H, J6a ,6b = 12.3, J5 ,6a = 3.1 Hz, H-6a0), 4.42 (t,
0
0
0
0
0
0
J = 9.3 Hz, H-4), 4.31 (dd, 1H, J5 ,6b = 3.7 Hz, H-6b0), 2.65–2.55 (m,
0
0
2H, SCH2CH3), 1.25 (t, 3H, J = 7.4 Hz, SCH2CH3); 13C NMR
(150 MHz, CDCl3) d 96.72 (JC-1 ,H-1 = 176.2 Hz, C-10), 81.78 (JC-1,H-1
=
0
0
J4,5 = 10.1, J5,6a = 6.5, J5,6b = 1.9 Hz, H-5), 4.51 (dd, 1H, J6a ,6b = 11.5,
0
0
J5 ,6a = 4.8 Hz, H-6a0), 4.43 (dd, 1H, J5 ,6b = 7.7 Hz, H-6b0), 4.04 (dd,
1H, J6a,6b = 11.0 Hz, H-6a), 3.65 (dd, 1H, H-6b), 2.76–2.58 (m, 2H,
SCH2CH3), 1.35 (t, 3H, J = 7.4 Hz, SCH2CH3); 13C NMR (150 MHz,
168.3 Hz, C-1), 73.90 (C-4), 72.74 (C-3), 72.03 (C-2), 70.83 (C-20),
69.84 (C-30), 69.17 (C-50), 69.08 (C-40), 68.62 (C-5), 63.54 (C-6),
62.44 (C-60), 24.33 (SCH2CH3), 14.69 (SCH2CH3); ESI-HRMS calcd
for C63H58NO17S [M+NH4]+: 1132.3425; found: 1132.3400; Anal.
Calcd for C63H54O17S: C, 67.85; H, 4.88. Found: C, 67.87; H, 4.80.
Compound 21: Rf = 0.5 (19:1 toluene–EtOAc); Mp 146–148 °C
0
0
0
0
CDCl3) d 96.25 (JC-1 ,H-1 = 173.7 Hz, C-10), 81.10 (JC-1,H-1 = 170.0 Hz,
C-1), 71.57 (C-2), 70.84 (C-3), 69.30 (C-40), 69.17 (C-4), 69.08 (C-
20), 68.71 (C-5), 68.42 (C-30), 67.18 (C-50), 65.98 (C-6), 62.84 (C-
60), 23.93 (SCH2CH3), 14.45 (SCH2CH3); ESI-HRMS calcd for
0
0
(MeOH); [
a]
+69.6 (c 1.0, CHCl3); lit.33, mode of preparation and
D
C
63H58NO17S [M+NH4]+: 1132.3425; found: 1132.3422; Anal. Calcd
characterization data were not disclosed; 1H NMR (600 MHz,
CDCl3) d 6.08 (dd, 1H, J2 ,3 = 10.5, J3 ,4 = 9.6 Hz, H-30), 5.80 (t, 1H,
for C63H54O17S: C, 67.85; H, 4.88. Found: C, 67.82; H, 5.02.
0
0
0
0

ˇ
D. Sail, P. Kovác / Carbohydrate Research 357 (2012) 47–52
52
7. Weygand, F.; Ziemann, H. Ann. 1962, 657, 179–198.
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Compound 25: Rf = 0.5 (19:1 toluene–EtOAc); Mp 157–159 °C;
D
[a
]
+128.7 (c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3) d 6.06 (dd,
1H, J2 ,3 = 10.6, J3 ,4 = 3.4 Hz, H-30), 6.03 (dd, 1H, J4,5 = 1.2 Hz, H-
0
0
0
0
40), 5.85 (t, 1H, J = 9.6 Hz, H-3), 5.73 (dd, 1H, J1 ,2 = 3.7 Hz, H-20),
5.59 (t, 1H, J = 9.6 Hz, H-4), 5.49 (d, 1H, H-10), 5.33 (t, 1H,
J = 9.7 Hz, H-2), 4.74 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.66 (br t, 1H, H-50),
0
0
4.47 (dd, 1H, J6a ,6b = 11.4, J5 ,6a = 7.2 Hz, H-6a0), 4.31 (dd, 1H,
=
0
0
0
0
50,6b0
5.6 Hz, H-6b0), 4.06–3.98 (m, 2H, H-5, H-6a), 3.80–3.76 (m, 1H,
H-6b), 2.64 (q, 2H, J = 7.4 Hz, SCH2CH3), 1.16 (t, 3H, J = 7.4 Hz,
SCH2CH3); 13C NMR (150 MHz, CDCl3) d 96.57 (JC-1 ,H-1 = 173.7 Hz,
C-10), 83.64 (JC-1,H-1 = 153.0 Hz, C-1), 77.42 (C-5), 74.23 (C-3),
70.41 (C-2), 69.19 (C-40), 69.02 (C-20), 68.98 (C-4), 68.40 (C-30),
67.15 (C-50), 66.29 (C-6), 62.60 (C-60), 23.84 (SCH2CH3), 14.69
0
0
ˇ
18. Kovác, P. Carbohydr. Res. 1986, 153, 237–251.
(SCH2CH3); ESI-HRMS calcd for C63H58NO17
S
[M+NH4]+:
19. Gallo-Rodriguez, C.; Varela, O.; de Lederkremer, R. M. Carbohydr. Res. 1998, 305,
163–170.
1132.3425; found: 1132.3397; Anal. Calcd for C63H54O17S: C,
67.85; H, 4.88. Found: C, 67.96; H, 5.15.
ˇ
20. Ziegler, T.; Kovác, P.; Glaudemans, C. P. J. Liebigs Ann. Chem. 1990, 613–615.
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Acknowledgement
ˇ
25. Kovác, P.; Glaudemans, C. P. J.; Guo, W.; Wong, T. C. Carbohydr. Res. 1985, 140,
This research was supported by the Intramural Research Pro-
gram of the NIH, NIDDK.
299–311.
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27. Ness, R. K.; Fletcher, H. G.; Hudson, C. S. J. Am. Chem. Soc. 1950, 72, 2200–2205.
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