Intermolecular aglycon transfer of ethyl thioglycosides can be prevented by judicious choice of protecting groups

Article abstract of DOI:10.1016/S0008-6215(00)00252-4

Unexpected intermolecular aglycon transfer occurred in chemoselective glycosylations using glycosyl fluorides or trichloroacetimidates as glycosyl donors and partially protected thioglycosides as glycosyl acceptors. It is shown that this problem can be addressed by fine-tuning of the reactivity of the anomeric thioalkyl moiety and hydroxyl of the acceptor.

Full text of DOI:10.1016/S0008-6215(00)00252-4

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Carbohydrate Research 329 (2000) 709–715
Intermolecular aglycon transfer of ethyl thioglycosides
can be prevented by judicious choice of protecting
groups
Tong Zhu, Geert-Jan Boons *
Complex Carbohydrate Research Center, Uni6ersity of Georgia, 220 Ri6erbend Road, Athens, GA 30602-4712, USA
Received 15 June 2000; accepted 18 August 2000
Abstract
Unexpected intermolecular aglycon transfer occurred in chemoseletive glycosylations using glycosyl fluorides or
trichloroacetimidates as glycosyl donors and partially protected thioglycosides as glycosyl acceptors. It is shown that
this problem can be addressed by fine-tuning of the reactivity of the anomeric thioalkyl moiety and hydroxyl of the
acceptor. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Chemoselective glycosylation; Thioglycoside; Oligosaccharide; Lewis antigens
quires for hydroxyl differentiation and manip-
1. Introduction
ulation. Thioglycosides can also act as
glycosyl acceptors and can be used in combi-
nation with a range of different donors includ-
ing trichloroacetimidates, glycosyl fluorides,
bromides, sulfoxides and selenoglycosides [2–
4]. In the presence of soft electrophiles, how-
ever, thioglycosides can be activated and used
as glycosyl donors. These chemical features
allow a chemoselective glycosylation strategy
whereby a thioglycoside first acts as a glycosyl
acceptor and in a subsequent glycosylation as
a donor. Such a sequence of reactions is very
attractive since time-consuming functional
group manipulations at the anomeric center
are avoided. Nevertheless, unexpected side re-
actions may occur when unreactive thioglyco-
syl acceptors are employed in glycosylations.
For example, Leigh and co-workers [5] re-
ported an intermolecular aglycon transfer of
ethyl 1-thiorhamnopyranosyl acceptors when
Koenigs–Knorr or Helferich glycosylation
conditions were employed. Intermolecular
Oligosaccharides are involved in many vital
biological processes [1], and not surprisingly,
there is increased demand for efficient meth-
ods for their chemical synthesis. The chemical
synthesis of complex oligosaccharides requires
highly convergent strategies. In such strategies
most of the synthetic effort is directed towards
the preparation of saccharide building blocks
that can be assembled into complex structures
using a minimum number of synthetic steps
[2]. Alkyl and aryl thioglycosides [3] have
emerged as versatile building blocks for con-
vergent oligosaccharide assembly. Due to their
excellent chemical stability, anomeric thio
groups offer efficient protection of anomeric
centers and are stable under many reaction
conditions that protecting group chemistry re-
* Corresponding author. Tel.: +1-706-5424401; fax: +1-
706-5424412.
E-mail address: gjboons@ccrc.uga.edu (G.-J. Boons).
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00252-4

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T. Zhu, G.-J. Boons / Carbohydrate Research 329 (2000) 709–715
aglycon transfer of a phenyl 1-thiogalac-
tosamide derivative using a trichloroacetimi-
date donor has also been reported [6,7].
In this paper, we describe an unexpected
intermolecular aglycon transfer when a galac-
tosyl fluoride or trichloroacetimidate donor
was coupled with a partially protected ethyl
1-thioglucosamine acceptor. It is shown that
this undesirable transfer reaction can be
avoided by a judicious choice of protecting
groups.
The known thioglycoside
1
[9] was
treated with FmocCl in pyridine to give com-
pound 2 in a yield of 94%. The benzylidene
acetal of 2 was regioselectively cleaved by
treatment with NaCNBH3 and HCl–Et2O in
THF [10] to give compound 3 bearing a C-4
hydroxyl.
N-Iodosuccinimide
(NIS)–
trimethylsilyl trifluoromethanesulfonate (TM-
SOTf) [11] mediated coupling of compound 3
with 4 gave disaccharide 5 as a sole product in
a yield of 84%. This glycosylation exploits the
higher reactivity of 6-deoxy thioglycosides
compared to their 6-hydroxy counterparts
[12]. The Fmoc group of compound 5 was
efficiently removed by treatment with triethyl-
amine in dichloromethane (Scheme 1). Cou-
pling of acceptor 6 with trichloroacetimidate 7
in the presence of TMSOTf [13] at rt did not
afford a trisaccharide, but instead thiogly-
coside 8 (92% with respect to acceptor) and
trichloroacetamide 9 (59%) were isolated.
(Scheme 2). A Cp2ZrCl2–AgOTf [14] medi-
ated coupling of glycosyl fluoride 10 with
disaccharide 6 did not give the desired trisac-
charide either, and this reaction also gave
thioglycoside 8 and degradation products
derived from the glycosyl acceptor.
2. Results and discussion
As part of a program to develop fully syn-
thetic tumor vaccines, we embarked on the
synthesis of oligosaccharide fragments derived
from Lewis antigens. A chemoselective glyco-
sylation strategy was designed where key thio-
glycoside 3 first acts as an acceptor leading to
core Lewis structures. At an appropriate
stage, however, the resulting complex thiogly-
cosides can be used as glycosyl donors for
glycosylations with Lewis- or lactosyl accep-
tors to give complex Lewis oligosaccharides.
In addition, the 9-fluorenylmethylcarbonyl
(Fmoc) group of 3 was selected as an attrac-
tive temporary hydroxyl-protecting group be-
cause it is remarkably stable under Lewis acid
conditions used in glycosylations but can be
cleaved under very mild basic conditions with-
out affecting other base-sensitive functionali-
ties [8]. The Fmoc group is also orthogonal
with the levulinoyl (Lev) and diethylisopropyl-
silyl (DEIPS) groups [8], and it is envisaged
that these functionalities will be employed for
future synthesis of the Lewis antigens.
The unusual aglycon transfer observed in
these reactions was rationalized as follows.
The acetoxonium ion 11, which was formed
after activation of glycosyl donor, reacts with
the anomeric thio alkyl moiety of 6 instead of
its hydroxyl, leading to the formation of b-
thioglycoside 8. The reactive intermediate 12
can either decompose or be trapped by a
nucleophile. In the coupling of 6 with 7, 2,2,2-
trichloro-N-trimethylsilylacetamide served as
a nucleophile to give the trichloroacetamide
derivative 9 (Scheme 3).
Our attention was turned to finding a solu-
tion for the unwanted transfer. It is well
known that the hydroxyl of disaccharide 6 is
of low reactivity due to the presence of the
bulky phthalimido group at C-2 [15], and this
feature may explain the preferred attack at the
anomeric thio group. The sterically less de-
manding trichloroethoxycarbonyl (Troc) was
selected as the amino protecting group ensur-
ing higher glycosyl accepting properties of the
C-3 hydroxyl of the glucosamine unit. A care-
ful review of previously reported syntheses of
Scheme 1. Reagents and conditions: (i) FmocCl, Py 94%; (ii)
,
NaCNBH3, HC–Et2O, THF, 3 A MS, 82%; (iii) NIS, TM-
,
SOTf, toluene, −5 °C, 4 A MS, 84%; (iv) Et3N, DCM, 88%.

T. Zhu, G.-J. Boons / Carbohydrate Research 329 (2000) 709–715
711
,
,
Scheme 2. Reagents and conditions: (i) TMSOTf, 4 A MS, DCM; (ii) Cp2ZrCl2, AgOTf, 4 A MS, DCM.
Scheme 3. A proposed mechanism for intramolecular aglycon transfer.
Lewisa antigens indicated that glucosamine
derivatives protected with a 4,6-O-benzylidene
functionality were most commonly used [16].
Possibly, the C-3 hydroxyl is more accessible
because the benzylidene acetal cannot freely
rotate and block this position. Furthermore, it
is well known that cyclic protecting groups
reduce anomeric reactivity [17]. To this end,
N-Troc protected thioglycoside 13 was em-
ployed as a glycosyl acceptor but, unfortu-
nately, coupling with trichloroacetimidate 7 in
the presence of TMSOTf did not give the
desired product, and again thioglycoside 8 was
obtained (yield 93% based on acceptor)
(Scheme 4). The outcome of this glycosylation
indicated that the anomeric thio moiety is still
,
Scheme 4. Reagents and conditions: (i) TMSOTf, 4 A MS,
DCM.
more nucleophilic than the C-3 hydroxyl. This

712
T. Zhu, G.-J. Boons / Carbohydrate Research 329 (2000) 709–715
observation may be explained by the finding
of Wong and co-workers that N-Troc pro-
tected thioglycosides are approximately 30
times more reactive than their phthalimido
analogues [18]. Thus, the reactivity of both the
C-3 hydroxyl and the anomeric thio moiety
were enhanced still leading to the undesired
reaction pathway.
spectrometer equipped with Sun workstations.
1
For H and 13C NMR spectra recorded in
CDCl3, chemical shifts (l) are given in ppm
relative to solvent peaks (1H, l 7.26; 13C, l
77.3) as internal standard. Negative-ion ma-
trix-assisted laser-desorption ionization time-
of-flight (MALDI-TOF) mass spectra were
recorded using an HP-MALDI 2030A instru-
ment with a gentisic acid matrix. Optical rota-
tions were measured on a Jasco P-1020
polarimeter.
A judicious choice of protecting groups is
needed to tune the reactivity of the anomeric
thio moiety and hydroxyl of the acceptor. An
appropriate balance of reactivities may be
achieved by employing the phthaloyl as N-
protecting group to deactivate the anomeric
center of the thioglycoside and a 4,6-O-ben-
zylidene acetal to enhance the reactivity of C-3
hydroxyl. Indeed, TMSOTf-mediated cou-
pling of 1 with 7 gave only coupling product
14, and in this case formation of thioglycoside
8 was not observed. Orthoester 14 was con-
verted easily to disaccharide 15 by TMSOTf-
catalyzed rearrangement (Scheme 4). Lewis
antigens can be obtained easily from disaccha-
ride 15 by regioselective opening of the ben-
zylidene acetal, followed by glycosylation [19].
In conclusion, it is shown that undesired
intermolecular aglycon transfer can be
avoided by a careful choice of protecting
groups that control anomeric reactivities of
glycosyl donor and acceptor and nucleophilic-
ity of the hydroxyl of the acceptor.
Ethyl 6-O-benzyl-3-O-(9-fluorenylmethoxy-
carbonyl)-2-deoxy-2-phthalimido-1-thio-i- -
D
glucopyranoside (3).—To a stirred solution of
compound 1 (0.44 g, 1.0 mmol) in pyridine (3
mL) was added FmocCl (0.52 g, 2.0 mmol),
and the reaction mixture was stirred at rt for 1
h. Methanol (2 mL) was added, and the sol-
vents were evaporated under reduced pressure.
The residue was diluted with CH2Cl2 (50 mL)
and washed successively with water (2×20
mL) and brine (20 mL). The organic layer was
concentrated under reduced pressure and the
crude product was purified by column chro-
matography (silica gel, 1:5, EtOAc–hexanes)
to give 2 as a colorless syrup (0.62 g, 94%).
A solution of hydrogen chloride in diethyl
ether (2 M, 7 mL) was added to a solution of
compound 2 (0.62 g, 0.94 mmol) and sodium
cyanoborohydride (0.88 g, 14 mmol) in THF
,
(10 mL) containing 3 A molecular sieves (300
mg). The mixture was stirred until the evolu-
tion of gas had ceased. The reaction mixture
was filtered, and the filtrate was co-evaporated
with MeOH (3×10 mL). The residue was
diluted with CH2Cl2 (50 mL) and washed suc-
cessively with water (2×20 mL) and brine (15
mL). The organic layer was dried (MgSO4)
and concentrated under reduced pressure. The
resulting syrup was applied to a column of
silica gel that was eluted with 1:3 EtOAc–hex-
anes to give 3 as a white foam (0.51 g, 82%).
1H NMR (CDCl3, 300 MHz): l 7.84–7.19 (m,
17 H, ArꢀH), 5.64 (dd, 1 H, J2,3 10.4, J3,4 10.0
Hz, H-3), 5.50 (d, 1 H, J1,2 10.4 Hz, H-1), 4.64
(AB q, 2 H, JAB 12.1 Hz, OCH2Ph), 4.46 (t, 1
H, H-2), 4.17 (d, 2 H, J 8.4 Hz, CH2O
(Fmoc)), 3.98–3.78 (m, 5 H, H-4, H-5, H-6a,
H-6b, H-9 (Fmoc)), 3.10 (s, 1 H, OH), 2.80–
2.61 (m, 2 H, SCH2), 1.23 (t, 3 H, J 7.4 Hz,
3. Experimental
Chemicals were purchased from Aldrich
and Fluka and used without further purifica-
tion. Molecular sieves were activated at
350 °C for 3 h in vacuo. Dichloromethane was
,
distilled from CaH2 and stored over 4 A
molecular sieves. All the reactions were per-
formed under anhyd conditions and moni-
tored by TLC on Kieselgel 60 F254 (E. Merck).
Detection was by examination under UV light
(254 nm) and by charring with 10% H2SO4 in
MeOH. Flash chromatography was performed
on silica gel (E. Merck, mesh 70–230). Ex-
tracts were evaporated under reduced pressure
at B40 °C (bath). H NMR and 13C NMR
1
spectra were recorded on a Varian Mercury
300 spectrometer and a Varian Inova 500

T. Zhu, G.-J. Boons / Carbohydrate Research 329 (2000) 709–715
713
SCH2CH3). 13C NMR (CDCl3, 75 MHz): l
168.1, 167.4 (2 C, CꢁO, Phth), 155.3 (CꢁO,
Fmoc), 143.3, 143.2, 141,3, 141.2, 137.8,
134.4, 134.2, 131.9, 131.4, 128.7, 128.1, 127.8,
127.4, 125.4, 125.3, 123.9, 123.8, 120.1 (24 C,
ArꢀC), 81.3 (C-1), 78.4 (C-3), 78.3 (C-5), 74.1
(OCH2Ph), 71.7 (C-4), 70.6 (2 C, CH2O
(Fmoc), C-6), 53.9 (C-2), 46.8 (C-9, Fmoc),
24.5 (SCH2), 15.3 (SCH2CH3). MALDI-TOF
MS: m/z 688 [M+Na]+. Anal. Calcd for
C38H35NO8S: C, 68.56; H, 5.30; N, 2.10.
Found: C, 68.62; H, 5.19; N, 2.12.
127.7, 127.6, 127.4, 125.4, 125.3, 123.7, 123.5,
119.9 (42 C, ArꢀC), 100.1 (C-1%), 80.8 (C-1),
79.7 (C-5), 79.5 (C-3%), 78.0 (C-3), 77.7 (C-4%),
76.9 (C-4), 76.6 (C-2%), 75.1 (OCH2Ph), 74.3
(OCH2Ph), 73.5 (OCH2Ph), 73.0 (OCH2Ph),
70.4 (CH2O, Fmoc), 69.3 (C-6), 67.8 (C-5%),
54.4 (C-2), 46.6 (C-9, Fmoc), 24.2 (SCH2),
16.8 (C-6%), 15.4 (SCH2CH3). MALDI-TOF
MS: m/z 1104.3 [M+Na]+. Anal. Calcd for
C65H63NO12S: C, 72.14; H, 5.87; N, 1.29.
Found: C, 72.28; H, 6.02; N, 1.17.
Ethyl 6-O-benzyl-2-deoxy-2-phthalimido-4-
O-(2,3,4-tri-O-benzyl-h-
thio-i-
L
-fucopyranosyl)-1-
Ethyl 6-O-benzyl-3-O-(9-fluorenylmethoxy-
carbonyl)-2-deoxy-2-phthalimido-4-O-(2,3,4-
D
-glucopyranoside (6).—Triethylamine
(1 mL) was added to a solution of compound
5 (60 mg, 0.055 mmol) in CH2Cl2 (2 mL).
After stirring for 2 h, TLC analysis (1:2
EtOAc–hexanes) indicated the completion of
the reaction. The reaction mixture was con-
centrated under reduced pressure, and the
crude product was purified by silica gel
column chromatography (1:3 EtOAc–hex-
anes) to give 6 as a colorless syrup (42 mg,
tri-O-benzyl-h-
L
-fucopyranosyl)-1-thio-i- -
D
glucopyranoside (5).—A solution of com-
pound 4 (48 mg, 0.10 mmol) and 3 (44 mg,
0.066 mmol) in toluene (3 mL) was stirred in
,
the presence of 4 A molecular sieves (100 mg,
powdered) for 15 min. The mixture was
cooled (−5 °C), and NIS (25 mg, 0.11 mmol)
and TMSOTf (0.5 mL, 2.8 mmol) were added.
After 5 min, the reaction mixture was diluted
with CH2Cl2 (40 mL) and filtered, and the
filtrate was washed successively with aq
sodium thiosulfate (15%, 25 mL), water (20
mL) and brine (15 mL). The organic phase
was dried (MgSO4) and filtered, and the
filtrate was concentrated in vacuo. The crude
product was purified by silica gel column
chromatography (1:3 EtOAc–hexanes) to give
1
88%). [h]2D5 −21.4° (c 0.2, CH2Cl2). H NMR
(CDCl3, 500 MHz): l 7.90–7.26 (m, 24 H,
ArꢀH), 5.33 (d, 1 H, J1,2 10.1 Hz, H-1), 5.00
(d, 1 H, J1%,2% 3.8 Hz, H-1%), 4.97, 4.63 (AB q, 2
H, JAB 11.5 Hz, OCH2Ph), 4.85, 4.76 (AB q, 2
H, JAB 11.5 Hz, OCH2Ph), 4.79, 4.68 (AB q, 2
H, JAB 12.0 Hz, OCH2Ph), 4.44 (AB q, 2 H,
JAB 12.0 Hz, OCH2Ph), 4.37 (dd, 1 H, J2,3 10.1
Hz, J3,4 8.6 Hz, H-3), 4.28 (t, 1 H, H-2), 4.08
(dd, 1 H, J2%,3% 10.6 Hz, H-2%), 4.05 (q, 1 H, J5%,6%
6.2 Hz, H-5%), 3.96 (d, 1 H, J5,6a 10.1 Hz,
H-6a), 3.90 (dd, 1 H, J3%,4% 2.4 Hz, H-3%), 3.82
(dd, 1 H, J5,6b 5.3 Hz, H-6b), 3.76 (dd, 1 H,
H-5), 3.67 (d, 1 H, H-4%), 3.55 (dd, 1 H, J4,5
9.1 Hz, H-4), 2.78–2.63 (m, 2 H, SCH2), 1.24
(t, 3 H, J 7.2 Hz, SCH2CH3), 1.09 (d, 3 H,
H-6%). 13C NMR (CDCl3, 75 MHz): l 168.5,
168.0 (2 C, CꢁO, Phth), 138.9, 138.7, 138.5,
134.2, 132.0, 128.6, 128.5, 128.4, 128.1, 128.0,
127.8, 127.7, 127.6, 124.0, 123.3 (30 C, ArꢀC),
100.2 (C-1%), 82.8 (C-4), 81.0 (C-1), 79.1 (C-3%),
79.0 (C-5), 77.7 (C-4%), 76.1 (C-2%), 75.3
(OCH2Ph), 74.0 (OCH2Ph), 73.5 (OCH2Ph),
73.4 (OCH2Ph), 71.8 (C-3), 69.5 (C-6), 68.4
(C-5%), 55.5 (C-2), 24.2 (SCH2), 17.1 (C-6%),
15.4 (SCH2CH3). MALDI-TOF MS: m/z
1
5 as a colorless syrup (60 mg, 84%). H NMR
(CDCl3, 500 MHz): l 7.74–7.17 (m, 32 H,
ArꢀH), 5.59 (dd, 1 H, J2,3 10.0, J3,4 8.7 Hz,
H-3), 5.43 (d, 1 H, J1,2 10.5 Hz, H-1), 5.09 (d,
1 H, J1%,2% 3.6 Hz, H-1%), 4.89, 4.56 (AB q, 2 H,
JAB 11.4 Hz, OCH2Ph), 4.79, 4.63 (AB q, 2 H,
JAB 11.4 Hz, OCH2Ph), 4.75, 4.68 (AB q, 2 H,
JAB 12.3 Hz, OCH2Ph), 4.43 (t, 1 H, H-2),
4.40 (AB q, 2 H, JAB 12.3 Hz, OCH2Ph), 4.05
(dd, 1 H, J 7.8 10.5 Hz, CHO (Fmoc)), 4.00
(dd, 1 H, J2%,3% 10.0 Hz, H-2%), 3.95–3.75 (m, 7
H, H-6a, H-4, H-5%, CHO (Fmoc), H-3%, H-5,
H-6b), 3.71 (t, 1 H, J 7.3 Hz, H-9 (Fmoc)),
3.57 (s, 1 H, H-4%), 2.73–2.59 (m, 2 H, SCH2),
1.17 (t, 3 H, J 7.3 Hz, SCH2CH3), 0.96 (d, 3
H, J 6.4 Hz, H-6%). 13C NMR (CDCl3, 75
MHz): l 168.0, 167.2 (2 C, CꢁO, Phth), 154.9
(CꢁO, Fmoc), 143.3, 143.2, 141.2, 141.0,
138.8, 138.7, 138.6, 134.3, 134.0, 131.9, 131.2,
128.8, 128.5, 128.4, 128.3, 128.2, 127.9, 127.8,
882.0
[M+Na]+.
Anal.
Calcd
for
C50H53NO10S: C, 69.83; H, 6.21; N, 1.63.
Found: C, 69.59; H, 6.16; N, 1.72.

714
T. Zhu, G.-J. Boons / Carbohydrate Research 329 (2000) 709–715
added. The reaction mixture was diluted with
N-Trichloroacetyl-6-O-benzyl-2-deoxy-2-
phthalimido-4-O-(2,3,4-tri-O-benzyl-h- -fuco-
pyranosyl)-i-
L
CH2Cl2 (30 mL) and filtered, and the filtrate
was washed successively with satd aq
NaHCO3 (25 mL), water (20 mL) and brine
(15 mL). The organic phase was dried
(MgSO4) and filtered, the filtrate was concen-
trated in vacuo. Purification of the residue by
silica gel column chromatography (1:2
EtOAc–hexanes) gave 14 as a colorless syrup
(77 mg, containing 5% of 15), which was
dissolved in dry CH2Cl2 (2 mL). Molecular
D
-glucopyranosylamine (9).—To
a mixture of 7 (34 mg, 0.07 mmol) and 6 (40
mg, 0.046 mmol) in CH2Cl2 (2 mL) in the
,
presence of 4 A molecular sieves (100 mg,
powdered) was added TMSOTf (0.5 mL, 2.8
mmol) at rt. After 5 min Et3N was added for
neutralization, and the mixture was diluted
with CH2Cl2 (40 mL). The molecular sieves
were removed by filtration, and the filtrate
was concentrated under reduced pressure. Sil-
ica gel column chromatography (1:3 EtOAc–
,
sieves (4 A, 100 mg) were added, and the
mixture was stirred at rt for 30 min. TMSOTf
(1 mL, 5.6 mmol) was added, and the mixture
was stirred for 16 h. The reaction mixture was
diluted with CH2Cl2 (30 mL) and filtered, and
the filtrate was concentrated in vacuo. The
crude product was applied to a silica gel
column that was eluted with 1:2 EtOAc–hex-
anes to give compound 15 as a white foam (41
hexanes),
followed
by
size-exclusion
chromatography (LH-20, 1:1 MeOH–CH2Cl2)
gave compound 8 as a white solid (16 mg,
92%) and 9 as a white foam (26 mg, 59%).
1
Analytical data for compound 9: H NMR
(CDCl3, 500 MHz): l 7.88–7.18 (m, 25 H, 24
ArꢀH, NH), 5.74 (dd, 1 H, J1,2 10.3 Hz, J1,NH
9.3 Hz, H-1), 5.00 (d, 1 H, J1%,2% 3.9 Hz, H-1%),
4.95, 4.60 (AB q, 2 H, JAB 11.3 Hz, OCH2Ph),
4.82, 4.75 (AB q, 2 H, JAB 11.8 Hz, OCH2Ph),
4.79, 4.65 (AB q, 2 H, JAB 11.8 Hz, OCH2Ph),
4.70 (dd, 1 H, J2,3 10.3 Hz, J3,4 8.8 Hz, H-3),
4.38 (AB q, 2 H, JAB 12.3 Hz, OCH2Ph), 4.21
(t, 1 H, H-2), 4.08 (dd, 1 H, J2%,3% 10.3 Hz,
H-2%), 4.05 (q, 1 H, J5%,6% 6.4 Hz, H-5%), 3.91
(dd, 1 H, J3%,4% 2.5 Hz, H-3%), 3.85–3.81 (m, 3
H, H-6a, H-6b, H-5), 3.67 (d, 1 H, H-4%), 3.63
(t, 1 H, J4.5 8.8 Hz, H-4), 1.08 (d, 3 H, H-6%).
Selected 13C NMR (CDCl3, 125 MHz): l
100.2 (C-1%), 81.7 (C-4), 79.0 (C-3%), 78.2 (C-1),
77.5 (C-4%), 76.7 (C-5), 75.7 (C-2%), 75.1
(OCH2Ph), 73.8 (OCH2Ph), 73.5 (OCH2Ph),
73.4 (OCH2Ph), 69.7 (C-3), 68.4 (C-6), 68.3
(C-5%), 55.8 (C-2), 16.7 (C-6%). MALDI-TOF
MS: m/z 983.2 [M+Na]+. Anal. Calcd for
C50H49Cl3N2O11: C, 62.54; H, 5.14; N, 2.92.
Found: C, 62.38; H, 5.17; N, 2.88.
1
mg, 53%). [h]2D5 −20.4° (c 0.3, CH2Cl2). H
NMR (CDCl3, 500 MHz): l 7.94–7.34 (m, 9
H, arom), 5.57 (s, 1 H, PhCH), 5.28 (d, 1 H,
J 9.7 Hz, H-1), 5.19 (d, 1 H, J3%,4% 3.4 Hz,
H-4%), 4.98 (dd, 1 H, J1%,2% 7.8 Hz, J2%,3% 10.2 Hz,
H-2%), 4.77 (t, 1 H, J2,3, J3,4 9.7 Hz, H-3), 4.73
(dd, 1 H, H-3%), 4.55 (d, 1 H, H-1%), 4.42–4.37
(m, 2 H, H-2, H-6%a), 4.03 (dd, 1 H, J5%,6%a 8.3
Hz, J6%a,6%b 11.2 Hz, H-6%a), 3.85–3.80 (m, 3 H,
H-4, H-6b, H-6%b), 3.70 (ddd, 1 H, H-5), 3.48
(ddd, 1 H, H-5%), 2.76–2.57 (m, 2 H, SCH2),
2.07, 1.91, 1.84, 1.57 (4 s, 12 H, Ac), 1.18 (t, 3
H, J 7.3 Hz, SCH2CH3). 13C NMR (CDCl3, 75
MHz): l 170.4–123.4 (18 C, CꢁO, ArꢀC),
101.7, 100.6, 82.0, 81.2, 76.7, 71.3, 70.9, 70.6,
69.5, 68.9, 66.9, 61.1, 54.5, 24.2, 21.0, 20.9,
20.8, 20.4, 15.1. MALDI-TOF MS: m/z 794
[M+Na]+. Anal. Calcd for C37H41NO15S: C,
57.58; H, 5.35; N, 1.81. Found: C, 57.83; H,
5.04; N, 1.66.
Ethyl 4,6-O-benzylidene-2-deoxy-2-phthal-
imido-3-O-(2,3,4,6-tetra-O-acetyl-i-
D
-galacto-
pyranosyl)-1-thio-i-
D
-glucopyranoside (15).—
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A solution of 7 (60 mg, 0.12 mmol) and 1 (44
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