Preparation of ethyl 2-azido-2-deoxy-1-thio-β-D-mannopyranosides, and their rearrangement to 2-S-ethyl-2-thio-β-D-mannopyranosylamines

Article abstract of DOI:10.1055/s-2006-926297

The synthesis of ethyl 2-azido-2-deoxy-1-thio-β-D-mannopyranosides 7-11, starting from appropriate synthons with gluco configuration, via S _N2 substitution at C(2), and their rearrangement to 2-S-ethyl-2-thio-β-D-mannopyranosylamines 12-14 are

Full text of DOI:10.1055/s-2006-926297

PAPER
699
Preparation of Ethyl 2-Azido-2-deoxy-1-thio-b-D-mannopyranosides, and
their Rearrangement to 2-S-Ethyl-2-thio-b-D-mannopyranosylamines
R
earrange
a
m
ent of
E
th
n
ylsulfanyl Group
VromC(1) to C(2)
o
n Sugar
Us
nits elý,a Anna Rohlenová,b Martina Džoganová,a Tomáš Trnka,a Iva Tišlerová,a David Šaman,b
Miroslav Ledvina*b
a
Department of Organic Chemistry, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6,
b
Czech Republic
Fax +420 220183560; E-mail: ledvina@uochb.cas.cz
Received 2 May 2005; revised 1 August 2005
Mannopyranosides, as well as 2-acetamido-2-deoxy-b-D-
Abstract: The synthesis of ethyl 2-azido-2-deoxy-1-thio-b-D-man-
mannopyranosides, have been considered to be one of the
most difficult types of O-glycosides to synthesize stereo-
nopyranosides 7–11, starting from appropriate synthons with gluco
configuration, via SN2 substitution at C(2), and their rearrangement
selectively. This derives from their unique structural fea-
tures (1,2-cis equatorial-oriented glycosidic bond), which
do not exert any stereoelectronic control by an anomeric
effect or participation of a neighboring group. Thus, from
the methods so far developed for the introduction of the b-
ManpNAc unit, the use the 2-(acyloxyimino)-2-deoxy-a-
D-arabino-hexopyranosyl bromide as glycosyl donor
proved to be superior.12,16–18 A different method for the in-
troduction of the b-ManpNAc element into the oligosac-
charide chain is the a posteriori introduction of the azido
group via SN2 substitution at C(2) in b-linked gluco-
sides.11,13,19 An approach based on the use of glycosyl do-
nors having a nonparticipating azido group at C(2) and a
1,2-trans-oriented leaving group, e.g., bromine20,21 or sul-
fanyl,22,23 at C(1) shows a limited b-selectivity depending
on the reactivity of the OH group of the glycosyl acceptor.
Therefore the formation of a-mannopyranosides is pre-
ferred with decrease of acceptor reactivity.21,23 The
synthesis of a-linked 2-acetamido-2-deoxy-D-manno-
pyranosides has received only little attention so far. From
common glycosylation methods only Koenigs-Knorr and
oxazoline methods were employed in the preparation of a
few simple alkyl a-D-mannopyranosides.24–26 These facts
motivated us to focus our attention on the preparation of
D-mannosamine synthons tailor-made for the stepwise
synthesis of oligosaccharides consisting of a- and
b(1→4)- or -(1→6)-linked 2-acetamido-2-deoxy-D-man-
nopyranose units.
to 2-S-ethyl-2-thio-b-D-mannopyranosylamines 12–14 are present-
ed.
Key words: carbohydrates, D-mannosamine, thioglycosides, ste-
reoselective synthesis, intramolecular rearrangements
2-Amino-2-deoxy-D-hexopyranosyl units (with gluco,
galacto, or manno configuration) occur frequently in var-
ious biologically important oligosaccharides and their
glycoconjugates, which have multiple biological func-
tions and activities.1,2 Due to the biological importance of
these oligosaccharide structures, a considerable effort has
been devoted to the search for efficient methods of their
synthesis.3
b-Linked N-acetyl-D-mannosamine units are an integral
part of a number of bacterial capsular polysaccharides4–8
and lipopolysaccharides.7–9 The immunological proper-
ties of capsular polysaccharides were exploited in the con-
struction of human vaccines.10–13 Oligosaccharides
containing b- and a-linked N-acetyl-D-mannosamine
units also seem to be potential mimics of natural ligands
for activated receptor of NK cells, taking into account the
fact that the binding activity of N-acetyl-D-mannosamine
is higher than that of N-acetyl-D-glucosamine and in the
case of chitooligomers, this activity increases with elon-
gation of the saccharide chain.14 Furthermore, oligosac-
charides consisting of a(1→4)-linked 2-amino-2-deoxy-
D-mannonopyranosyl units have an axially oriented gly-
cosidic bond and an equatorially oriented C(4)–O bond
and thus they satisfy the basic criteria for cyclization and
forming of 2-amino-2-deoxy-cyclomannine analogues of
cyclodextrins.15
An approach based on the introduction of the azido group
as non-participating masked amino function, exploiting
SN2 substitution in position C(2) of appropriate synthons
with gluco configuration was chosen for the synthesis of
the above-mentioned D-mannosamine building units. The
methods commonly used for the preparation of 2-azido-2-
deoxyhexoses, based on azidonitration of glycals,27–31
show a low manno stereoselectivity. Another recently
used general approach is represented by the diazo transfer
reaction of appropriate D-hexosamines.22,27,28
However, despite the biological significance of oligosac-
charides consisting of N-acetyl-D-mannosamine units,
both the chemistry of D-mannosamine and efficient, prac-
tical methods for incorporation of the D-mannosamine
motif into oligosaccharide chains remain scarce. b-D-
As the starting material for the preparation of the target
ethyl 2-azido-2-deoxy-1-thio-b-D-mannopyranosides, we
utilized 1,2,4,6-tetra-O-acetyl-3-O-benzyl-b-D-glucopyr-
anose (1). Compound 1 was prepared from 3-O-benzyl-D-
SYNTHESIS 2006, No. 4, pp 0699–0705
Advanced online publication: 11.01.2006
DOI: 10.1055/s-2006-926297; Art ID: T05705SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
6

700
J. Veselý et al.
PAPER
N3
O
AcO
AcO
BnO
N3
O
AcO
AcO
BnO
Ph
O
O
BnO
AcO
BnO
BnO
O
iv, v
i
O
SEt
OAc
8
+
SEt
SEt
AcO
AcO
7
11
2
1
i
ii
N3
N3
O
BnO
AcO
BnO
HO
HO
BnO
Ph
O
O
BnO
BnO
RO
BnO
iii
O
O
O
O
iii
SEt
SEt
SEt
SEt
OH
OH
10
8: R = H
ii
4
3
9: R = Ac
iv or v
Scheme 2 Reagents and conditions: i) Et3SiH, TFA, CH2Cl2, 0 °C
to r.t., 72%; ii) Ac2O, pyridine, r.t., 89%; iii) MCPBA, CH2Cl2,
–10 °C, 81%; iv) AlCl3, BH3·Me3N, 4Å MS, CH2Cl2–Et2O, 0 °C; v)
AcCl, sym-collidine, CH2Cl2, –60 °C, 62% (in two steps)
N3
O
Ph
O
O
BnO
Ph
O
O
BnO
vi
O
SEt
SEt
OR
7
5: R = Ms
6: R = Tf
oligosaccharides consisting of (1→4)-linked 2-amino-2-
deoxy-D-mannopyranosyl units (Scheme 2).
Scheme 1 Reagents and conditions: i) EtSH, TMSOTf, 4Å MS,
CH2Cl2, 0 °C, 79%; ii) MeONa, MeOH, r.t., 72%; iii) a,a-dimethoxy-
toluene, TfOH, CH2Cl2, Et3N, r.t., 84%; iv) MsCl, pyridine, 0 °C to
r.t., 84%; v) Tf2O, CH2Cl2–pyridine, 0 °C; vi) NaN3, DMF, 80 °C,
82% (71% in two steps from 4 through 6)
The reaction of 7 with aluminium(III) chloride and bo-
rane-trimethylamine complex in a mixture of CH2Cl2 and
Et2O led to a mixture of regioisomers, i.e., compound 8
and ethyl 2-azido-3,4-di-O-benzyl-2-deoxy-1-thio-b-D-
mannopyranoside. The latter was isolated from the mix-
ture as 6-O-acetate 11 by selective O-acetylation of its pri-
mary OH group with acetyl chloride in the presence of
sym-collidine at –60 °C.
glucose32 by modification of the procedure described in
the literature,33 i.e., O-acetylation with acetic anhydride in
pyridine in the presence of 4-(N,N-dimethylamino)pyri-
dine (DMAP), instead of O-acetylation in the presence of
sodium acetate, which led to a mixture of a- and b-ano-
mers.
Attempts to activate the ethylsulfanyl group of the pre-
pared 2-azido-2-deoxy-1-thio-b-D-mannopyranosides via
a sulfonium ion by routinely used glycosylation methods,
i.e., with MeOTf or dimethyl(methylthio)sulfonium trif-
late (DMTST) in the case of 7, 9 and 11, and with NIS/
TfOH and in the case of 9 and 11, were unsuccessful. Al-
so, the conversion of these compounds to glycosyl fluo-
rides by reaction with dimethyl(methylthio)sulfonium
tetrafluoroborate (DMTSF) did not work. Methanol and
cyclohexanol, respectively, were used as glycosyl accep-
tors. In general, b-anomers are considered to be more re-
active than a-anomers.22 The approach based on the
transformation of thioglycoside to sulfoxide and its subse-
quent activation with Tf2O36 has also led to negative re-
sults. Sulfoxide 10 was prepared by oxidation of 9 with
MCPBA.
An efficient Lewis acid catalyzed substitution of anomer-
ic acetate with ethanethiol requires 1,2-trans-acetate. For
the transformation of 1 to ethyl 1-thio-b-D-glucopyrano-
side (2) (Scheme 1), trimethylsilyl trifluoromethane-
sulfonate, instead of BF3·OEt2 as described in the
literature,34 was used as a promotor. Zemplén deacetyla-
tion of 2 gave ethyl 3-O-benzyl-1-thio-b-D-glucopyrano-
side (3) which was treated with a,a-dimethoxytoluene in
the presence of a catalytic amount of trifluoromethane-
sulfonic acid, to afford ethyl 3-O-benzyl-4,6-O-ben-
zylidene-1-thio-b-D-glucopyranoside (4). O-Mesyl and
O-trifluoromethanesulfonyl groups were used as leaving
groups in position C(2) of 4. Reaction of 4 with methane-
sulfonyl chloride in pyridine afforded crystalline 2-O-me-
syl derivative 5. 2-O-Trifluoromethanesulfonyl derivative
6, obtained by reaction of 4 with triflic anhydride in pyri-
dine and CH2Cl2 in form of an unstable syrupy product,
was used for the next step without further purification.
Treatment of 2-O-methanesulfonyl derivative 5 as well as
2-O-trifluoromethanesulfonyl derivative 6 with sodium
azide in dry DMF at 80 °C afforded the key ethyl 2-azido-
3-O-benzyl-4,6-O-benzylidene-2-deoxy-1-thio-b-D-man-
nopyranoside (7) in very good yields.
The deactivation of b-oriented alkylsulfanyl and sulfoxide
functionalities might be caused by significant interaction
between the axially oriented azido group at C(2) and the
equatorially linked sulfur at C(1) on the mannopyranose
skeleton. This observation motivated us to replace the azi-
do group at C(2) with the participating trichloroethoxy-
carbonylamino (NHTroc) or phthalimido (NPhth) group.
The attempt to transform azides 7 and 9 into the appropri-
ate amino derivatives was unsuccessful. Standard meth-
ods for the conversion of an azido group into an amino
group, i.e., in the case of 7 and 9 by reduction with H2S,
SnCl2/PhSH and Et3N, or LAH, and in the case of 9 by re-
duction with H2/PtO2 or BH3, led to complex mixtures.
Reduction of azido derivatives 7 and 9 with triphen-
ylphosphine gave the corresponding phosphine imides,
Reductive opening of the 4,6-O-benzylidene group of 7
with triethylsilane and trifluoroacetic acid in CH2Cl2,35
followed by 4-O-acetylation of obtained ethyl 2-azido-
3,6-di-O-benzyl-2-deoxy-1-thio-b-D-mannopyranoside
(8), gave glycosyl donor 9 designed for the synthesis of
Synthesis 2006, No. 4, 699–705 © Thieme Stuttgart · New York

PAPER
Rearrangement of Ethylsulfanyl Group from C(1) to C(2) on Sugar Units
701
N3
O
SEt
O
Ph
O
O
BnO
O
O
BnO
Ph
N
i,ii
SEt
NHTroc
N
N
N3
O
BnO
AcO
BnO
BnO
AcO
BnO
7
12
O
SEt
SEt
N3
O
SEt
O
BnO
AcO
BnO
BnO
AcO
BnO
9
9
i,ii
SEt
i
NHTroc
9
13
N2
+
H
SEt
O
BnO
AcO
BnO
N
N
BnO
AcO
BnO
BnO
AcO
BnO
O
O
NH2
SEt
SEt
H
14
B
A
Scheme 3 Reagents and conditions: i) Propane-1,3-dithiol, Et3N,
pyridine–H2O, r.t.; ii) TrocCl, pyridine, 0 °C to r.t., 79% (for 12),
64% (for 13), (in two steps)
SEt
O
SEt
O
BnO
AcO
BnO
BnO
AcO
BnO
N
H
which were resistant to hydrolysis and ammonolysis,37 as
well as to direct conversion into phthalimido derivatives
by their reaction with phthalic anhydride in the presence
of tetrabutylammonium cyanide.38
HN
D
C
SEt
O
SEt
O
BnO
AcO
BnO
BnO
AcO
BnO
On using propane-1,3-dithiol for the reduction of the azi-
do group,39 the reduction of derivatives 7 and 9 was fol-
lowed by migration of the ethylsulfanyl group at C(1) and
the amino group at C(2) with the retention of configura-
tion in both positions. Reduction of 7 or 9 with propane-
1,3-dithiol and Et3N in a mixture of pyridine and water,
and subsequent N-trocylation of the formed amino deriv-
atives, gave 3-O-benzyl-4,6-O-benzylidene-2-S-ethyl-2-
thio-b-D-mannopyranosyl-(2,2,2-trichloroethoxycarbon-
yl)amine (12) and 4-O-acetyl-3,6-di-O-benzyl-2-S-ethyl-
2-thio-b-D-mannopyranosyl-(2,2,2-trichloroethoxycarbo-
nyl)amine (13), respectively (Scheme 3).
NH
HN–
H–
H
F
E
H+
SEt
O
BnO
AcO
BnO
NH2
14
Scheme 4 Suggested mechanism of formation of compound 14
Unexpected products 12 and 13 can be attributed to the
formation of nitrene intermediate A (Scheme 4). The tau-
tomeric form B can be transformed via thiiranium ion C
into epimine D, which can undergo the ionization support-
ed by the repulsion of atoms of sulfur and oxygen in pyr-
anose rings. Intermediate E can be converted via imine F
into b-glycosylamine 14 under reduction conditions.
Therefore, the opening of the aziridine ring does not pro-
ceed by the Fürst–Plattner rule. The subsequent N-troc-
ylation of glycosylamines afforded 12 and 13,
respectively. Glycosyl amine 14 was isolated from the re-
action mixture before the trocylation step.
of appropriate synthons with gluco configuration, was
elaborated. A significant interaction between the axially
oriented azido group at C(2) and the equatorially oriented
alkylsulfanyl group at C(1) on the mannopyranose skele-
ton was observed. It results (a) in the deactivation of the
alkylsulfanyl leaving group in the glycosylation process
and (b) in the migration of both substituents at C(1) and at
C(2) with the retention of configuration in both positions,
under conditions of reduction of the azido group to the
amino group, to give 2-S-ethyl-2-thio-b-D-mannopyrano-
sylamines. The acquired knowledge expands the general
view of the transformations on the mannosamine skeleton.
For the structure determination of key compounds 12, 13
and 14, the 2D homo- and heterocorelated NMR spectra
and detailed analysis of coupling constants were em-
ployed. The results from 2D NMR ROESY experiments
as well as those from theoretical calculation of optimum
geometry using AM1 calculation supported b-configura-
tion of the above-mentioned compounds. Characteristic
H-1/H-3 and H-1/H-5 cross-peaks in ROESY NMR spec-
tra were observed.
Melting points were determined on a Kofler block and are uncor-
rected. Specific rotations were measured on a Perkin-Elmer 141 po-
larimeter at 25 °C. Elemental analyses were performed using a
Perkin Elmer 2400 II instrument. NMR spectra were recorded on a
Varian Unity Inova 400 FT spectrometer and a Bruker Avance 500
spectrometer in the FT mode in CDCl3 or (CD3)2SO, using (CH3)4Si
1
as internal standard for H NMR spectra and CDCl3 (d = 77.0) or
(CD3)2SO (d = 39.7) signals as standards for 13C NMR spectra. For
1
unambiguous assignment of signals in 13C NMR spectra, H- and
In summary, the synthesis of ethyl 2-azido-2-deoxy-1-
thio-b-D-mannopyranosides, via SN2 substitution at C(2)
13C-heterocorrelated 2D NMR spectra were measured by gHSQC
and gHMBC techniques using the standard pulse sequences deliv-
Synthesis 2006, No. 4, 699–705 © Thieme Stuttgart · New York

702
J. Veselý et al.
PAPER
ered by the producer of the spectrometer. The following typical pa-
rameters were used: spectral width in both f1 and f2 dimensions 5000
Hz and 17000 Hz, respectively, number of scans 16, number of in-
crements in f1 dimension 256, recycle delay 1 s, acquisition time 0.2
s, 90° pulse for 1H was 12.5 ms, data matrix for processing
2048 × 2048 datapoints. For processing, shifted sinebell weighting
function was used. Chemical shifts are given in ppm (d-scale) and
coupling constants (J) in Hz. Positive-ion FAB mass spectra were
measured on a BeqG-geometry mass spectrometer ZAB-EQ (VG
Analytical, Manchester, UK) using an M-Scan FAB gun (Xe, ener-
gy 8 keV) at an accelerating voltage of 8 kV. Samples were dis-
solved in CHCl3 or MeOH, and a mixture of glycerol and
thioglycerol or DMSO was used as matrix. TLC was performed on
DC-Alufolien Kieselgel 60 F254 (Merck, Darmstadt, Germany) or
Silufol UV254 (Kavalier, Votice, Czech Republic) silica gel sheets.
Preparative chromatography was performed on a silica gel column,
particle size 40–60 mm (Fluka, Neu-Ulm, Switzerland). Analytical
RP HPLC was performed using a Waters instrument (PDA detector,
software Milennium 32; Milford, Massachusetts, USA) equipped
with a Nova-Pak C18 column (150 × 3.9 mm), particle size 4 mm.
Preparative RP HPLC was performed on a column (250 × 25 mm)
filled with LiChrosorb RP-18, particle size 5 mm (Merck, Darm-
stadt, Germany). Solvents were evaporated on a rotary vacuum
evaporator at 40 °C. Analytical samples were dried at 6.5 Pa and
25 °C for 8 h. Petroleum ether is abbreviated as PE and had a bp of
40–65 °C.
1H NMR (400 MHz, DMSO-d6): d = 1.20 (t, J = 7.6 Hz, 3 H,
SCH2CH3), 2.57–2.73 (m, 2 H, SCH2CH3), 3.14–3.28 (m, 4 H, H-2,
H-3, H-4, H-5), 3.44 (dd, J = 11.8, 5.8 Hz, 1 H, H-6a), 3.68 (dd,
J = 11.8, 1.7 Hz, 1 H, H-6b), 4.32 (d, J = 9.4 Hz, 1 H, H-1), 4.79 (d,
J = 11.8 Hz, 1 H), 4.83 (d, J = 11.8 Hz, 1 H, C6H5CH2), 4.20–5.40
(br s, 3 H, 3 × OH), 7.20–7.25 (m, 1 H), 7.28–7.32 (m, 2 H), 7.40–
7.43 (m, 2 H, C6H5CH2).
13C NMR (100 MHz, DMSO-d6): d = 14.6, 22.9, 61.0, 69.7, 72.8,
73.9, 81.0, 85.0, 86.6, 127.0, 127.5 (2 C), 127.9 (2 C), 139.5.
MS (FAB+): m/z (%) = 337.2 [M+ + Na].
Anal. Calcd for C15H22O5S: C, 57.30; H, 7.05; S, 10.20. Found: C,
57.11; H, 6.98; S, 10.26.
Ethyl 3-O-Benzyl-4,6-O-benzylidene-1-thio-b-D-glucopyrano-
side (4)
To a stirred solution of compound 3 (15.0 g, 47.70 mmol) in anhyd
CH2Cl2 (300 mL), a,a-dimethoxytoluene (28 mL, 193.36 mmol)
and TfOH (0.4 mL, 4.58 mmol) were added. After 1 h, Et3N (1.6
mL, 11.48 mmol) was added, the reaction mixture was taken up in
CHCl3 (300 mL), washed with H2O (2 × 200 mL), dried (MgSO4)
and evaporated. Crystallization from of EtOAc–PE afforded 16.1 g
(84%) of compound 4.
25
Mp 139–140 °C; [a]D –61.1 (c 0.2, CHCl3) {Lit.34 mp 139 °C;
[a]D25 –46.2 (c 0.3, CHCl3).
IR (CHCl3): 3574 (OH), 654 (C–S), 1111, 1084, 1070, 1010, 994
(4,6-O-benzylidene), 3091, 3068, 3034, 1498, 1454, 914, 699
(PhCH2) cm–1.
Ethyl 2,4,6-Tri-O-acetyl-3-O-benzyl-1-thio-b-D-glucopyrano-
side (2)
To a stirred solution of 1,2,4,6-tetra-O-acetyl-3-O-benzyl-b-D-
glucopyranose32 (1; 4.4 g, 10.01 mmol) and 4 Å MS (3 g) in anhyd
CH2Cl2 (50 mL), ethanethiol (1.89 mL, 25.52 mmol) was added un-
der Ar. The reaction mixture was cooled to 0 °C and TMSOTf (1.9
mL, 10.48 mmol) was slowly added dropwise. After 2 h the reaction
mixture was filtered through celite, the filtrate was washed with sat.
aq NaHCO3 (2 × 20 mL) and H2O (2 × 20 mL), dried over (MgSO4)
and evaporated. Crystallization from the solvent mixture toluene–
heptane afforded 3.5 g (79%) of compound 2.
1H NMR (400 MHz, CDCl3): d = 1.32 (t, J = 7.5 Hz, 3 H,
SCH2CH3), 2.78–2.72 (m, 2 H, SCH2CH3), 3.50 (ddd, J = 10.2, 8.7,
5.0 Hz, 1 H, H-5a), 3.58 (t, J = 9.6 Hz, 1 H, H-2), 3.65–3.75 (m, 2
H, H-3, H-4), 3.78 (t, J = 10.4 Hz, 1 H, H-6a), 4.36 (dd, J = 10.5,
5.0 Hz, 1 H, H-6b), 4.47 (d, J = 9.8 Hz, 1 H, H-1), 4.82 (d, J = 11.8
Hz, 1 H), 4.98 (d, J = 11.8 Hz, 1 H) (C6H5CH2), 5.58 (s, 1 H,
C6H5CH), 7.28–7.51 (m, 10 H, C6H5CH2, C6H5CH).
13C NMR (100 MHz, CDCl3): d = 15.2, 24.6, 68.6, 70.8, 73.0, 74.7,
81.2, 81.5, 86.6, 101.3, 126.0 (2 C), 127.8, 128.1(2 C), 128.3 (2 C),
128.5 (2 C), 129.0, 137.2, 138.3.
Mp 112–114 °C; [a]D –32.1 (c 0.3, CHCl3) {Lit.34 mp 88–90 °C;
[a]D25 –33.2 (c 0.2, CHCl3}.
MS (FAB+): m/z (%) = 403.2 [M+ + H].
1H NMR (400 MHz, CDCl3): d = 1.26 (t, J = 7.2 Hz, 3 H,
SCH2CH3), 1.97 (s, 3 H, OAc), 2.02 (s, 3 H, OAc), 2.07 (s, 3 H,
OAc), 2.62–2.78 (m, 2 H, SCH2CH3), 3.61 (ddd, J = 9.9, 5.2, 2.4
Hz, 1 H, H-5), 3.71 (t, J = 9.2 Hz, 1 H, H-3), 4.12 (dd, J = 12.4, 5.3
Hz, 1 H, H-6a), 4.19 (dd, J = 12.4, 5.3 Hz, 1 H, H-6b), 4.40 (d,
J = 10.1 Hz, 1 H, H-1), 4.59 (d, J = 11.8 Hz, 1 H), 4.64 (d, J = 11.6
Hz, 1 H, C6H5CH2), 5.08 (t, J = 9.8 Hz, 1 H, H-2), 5.11 (t, J = 9.9
Hz, 1 H, H-4), 7.22–7.36 (m, 5 H, C6H5CH2).
Anal. Calcd for C22H26O5S: C, 65.65; H, 6.51; S, 7.97. Found: C,
65.19; H, 6.50; S, 7.82.
Ethyl 3-O-Benzyl-4,6-O-benzylidene-2-O-(methylsulfonyl)-1-
thio-b-D-glucopyranoside (5)
A solution of 4 (1.0 g, 2.48 mmol) in pyridine (10 mL) was cooled
to 0 °C and MsCl (0.39 mL, 4.97 mmol) was added dropwise. The
reaction mixture was warmed gradually and then stirred at r.t. for 24
h. The reaction mixture was evaporated and the residue was diluted
with CH2Cl2 (30 mL) and H2O (30 mL). The aqueous layer was ex-
tracted with CH2Cl2 (2 × 20 mL). The combined organic layers were
dried (MgSO4) and evaporated. Crystallization of the residue from
EtOH afforded 1.0 g (84%) of product 5.
13C NMR (100 MHz, CDCl3): d = 14.8, 20.7, 20.8, 20.9, 23.9, 62.5,
69.6, 71.2, 74.2, 76.2, 81.5, 83.7, 127.7 (2 C), 127.8, 128.4 (2 C),
137.7, 169.3, 169.3, 170.8.
MS (FAB+): m/z (%) = 441.2 [M+ + H].
Anal. Calcd for C21H28O8S: C, 57.26; H, 6.41; S, 7.28. Found: C,
57.18; H, 6.42; S, 7.11.
Mp 103–104 °C; [a]D25 –39 (c 0.4, CHCl3).
1H NMR (400 MHz, CDCl3): d = 1.30 (t, J = 7.3 Hz, 3 H,
SCH2CH3), 2.72–2.82 (m, 2 H, SCH2CH3), 3.00 (s, 3 H, OSO2CH3),
3.51 (ddd, J = 9.9, 9.2, 4.9 Hz, 1 H, H-5), 3.77 (t, J = 9.3 Hz, 1 H,
H-4), 3.78 (t, J = 10.2 Hz, 1 H, H-6a), 3.86 (ddd, J = 9.3, 7.8, 0.8
Hz, 1 H, H-3), 4.39 (dd, J = 10.7, 5.0 Hz, 1 H, H-6b), 4.57 (d,
J = 9.9 Hz, 1 H, H-1), 4.61 (dd, J = 10.0, 7.8 Hz, 1 H, H-2), 4.77 (d,
J = 10.8 Hz, 1 H), 4.98 (d, J = 10.8 Hz, 1 H) (C6H5CH2), 5.58 (s, 1
H, C6H5CH), 7.26–7.48 (m, 10 H, C6H5CH2, C6H5CH).
Ethyl 3-O-Benzyl-1-thio-b-D-glucopyranoside (3)
Compound 2 (35.0 g, 79.45 mmol) was dissolved in a solution of so-
dium methoxide in MeOH (0.01 M, 1200 mL). The reaction mixture
was stirred for 6 d at r.t. Then the reaction mixture was neutralized
by Dowex 50 (in pyridinium form) and evaporated. Crystallization
from 2-PrOH–PE afforded 18.0 g (72%) of compound 3.
Mp 100–102 °C; [a]D25 –67.8 (c 0.58, CHCl3).
13C NMR (100 MHz, CDCl3): d = 14.7, 24.1, 39.5, 68.4, 70.4, 75.0,
79.5, 80.0, 81.6, 84.0, 101.2, 125.9 (2 C), 127.9, 128.3 (2 C), 128.3
(2 C), 128.4 (2 C), 129.1, 136.8, 137.4.
IR (KBr): 3498, 3435, 3307 (OH), 3087, 3064, 3025, 1497, 1452
(PhCH2) cm–1.
Synthesis 2006, No. 4, 699–705 © Thieme Stuttgart · New York

PAPER
Rearrangement of Ethylsulfanyl Group from C(1) to C(2) on Sugar Units
703
MS (FAB+): m/z (%) = 481.2 [M+ + H].
were dissolved in anhyd CH2Cl2 (8 mL) and the solution was cooled
to –70 °C. AcCl (38 mL, 0.5 mmol) was added and the reaction mix-
ture was stirred for 1 h at –60 °C, then quenched with MeOH (1 mL)
and allowed to attain r.t. Progress of the reaction was monitored us-
ing TLC in toluene–EtOAc (5:1). The solvent was evaporated and
purification on a silica gel column (10 g) with toluene–EtOAc
(20:1) gave 147 mg (62%) of 11 and 65 mg (30%) of 8.
Anal. Calcd for C23H28O7S2: C, 57.48; H, 5.87; S, 13.34. Found: C,
57.44; H, 5.91; S, 13.27.
Ethyl 3-O-Benzyl-4,6-O-benzylidene-1-thio-2-O-[(trifluoro-
methyl)sulfonyl]-b-D-glucopyranoside (6) and Ethyl 2-Azido-3-
O-benzyl-4,6-O-benzylidene-2-deoxy-1-thio-b-D-mannopyrano-
side (7)
Method A: To a stirred solution of compound 4 (1.6 g, 3.98 mmol)
in anhyd CH2Cl2 (16 mL) and pyridine (1.6 mL) at 0 °C, Tf2O (1.0
mL, 5.94 mmol) was added dropwise under Ar. After 30 min, the
reaction mixture was treated with ice-cold sat. aq NaHCO3 (10 mL),
the organic layer was washed with H2O (30 mL), dried (MgSO4)
and evaporated to afford 6 as a solid.
Method B: TFA (80 mL, 1.08 mmol) was added dropwise to a solu-
tion of compound 7 (86 mg, 0.20 mmol) and triethylsilane (160 mL,
1.00 mmol) in CH2Cl2 (2 mL) at 0 °C. The reaction mixture was
warmed to r.t. and stirred for 1 h. Progress of the reaction was mon-
itored using TLC with toluene–EtOAc (5:1). The mixture was dilut-
ed with EtOAc (8 mL), washed with sat. aq. NaHCO3 (5 mL), H2O
(5 mL), dried (MgSO4) and evaporated. Chromatography of the res-
idue on a silica gel column (5 g) with toluene–EtOAc (12:1) afford-
ed 62 mg (72%) of compound 8 as colorless syrup.
MS (FAB+): m/z (%) = 385.1 [M+ – TfOH + H].
To a stirred solution of this residue in DMF (35 mL), NaN3 (1.6 g,
24.61 mmol) was added and the mixture was heated to 80 °C under
Ar overnight. After 16 h, the reaction mixture was taken up between
toluene (100 mL) and H2O (80 mL), the organic layer was washed
with H2O (80 mL), dried (MgSO4) and evaporated. Chromatogra-
phy of the residue on a silica gel column (40 g) with toluene–EtOAc
(25:1) gave 1.2 g (71%) of 7 as colorless oil.
Compound 8
[a]D25 +48 (c 0.4, CHCl3).
IR (CHCl3): 3592, 3513, 1054 (OH), 2110, 1265, 567 (N3) cm–1.
1H NMR (400 MHz, CDCl3): d = 1.25 (t, J = 7.6 Hz, 3 H,
SCH2CH3), 2.58–2.66 (m, 2 H, SCH2CH3), 3.09–3.13 (m, 1 H, H-
2), 3.74–3.78 (m, 2 H, H-6a, H-6b), 3.88–3.91 (m, 3 H, H-3, H-4,
H-5), 4.55 (d, J = 11.6 Hz, 1 H), 4.57 (d, J = 11.9 Hz, 1 H), 4.65 (d,
J = 12.1 Hz, 1 H), 4.70 (d, J = 11.4 Hz, 1 H, 2 × C6H5CH2), 5.55 (d,
J = 1.7 Hz, 1 H, H-1), 7.27–7.40 (m, 10 H, 2 × C6H5CH2).
13C NMR (100 MHz, CDCl3): d = 14.6, 27.1, 48.1, 67.8, 69.7, 71.8,
73.6, 73.7, 77.5, 90.7, 127.6, 127.6 (2 C), 128.1 (3 C), 128.3 (2 C),
128.6 (2 C), 137.6, 138.0.
Method B: Compound 5 (1.0 g, 2.08 mmol) was dissolved in anhyd
DMF (30 mL) and LiN3 (0.25 g, 5.19 mmol) was added. The mix-
ture was heated to 80 °C under Ar for 16 h. After cooling to r.t., the
reaction mixture was concentrated, the residue was diluted with
H2O (40 mL) and extracted with CH2Cl2 (2 × 40 mL). The combined
organic layers were dried (MgSO4) and evaporated. Column chro-
matography on silica gel (50 g) with toluene afforded 729 mg (82%)
of compound 7.
MS (FAB+): m/z (%) = 430.1 [M+ + H].
[a]D25 +124 (c 0.3, CHCl3).
Anal. Calcd for C22H27N3O4S: C, 61.52; H, 6.34; N, 9.78; S, 7.47.
Found: C, 61.49; H, 6.47; N, 9.90; S, 7.36.
IR (CHCl3): 2110, 1263, 566 (N3), 3091, 3068, 3035, 1497, 1454
(PhCH2) cm–1.
Compound 11
1H NMR (400 MHz, CDCl3): d = 1.27 (t, J = 7.3 Hz, 3 H,
SCH2CH3), 2.72 (q, J = 7.5 Hz, 2 H, SCH2CH3), 3.13 (dd, J = 4.0,
1.2 Hz, 1 H, H-2), 3.83 (t, J = 10.2 Hz, 1 H, H-4), 3.92–4.01 (m, 1
H, H-5), 4.06–4.14 (m, 2 H, H-6a, H-6b), 4.28 (dd, J = 10.2, 4.7 Hz,
1 H, H-3), 4.70 (d, J = 12.2 Hz, 1 H), 4.82 (d, J = 12.2 Hz, 1 H)
(C6H5CH2), 5.54 (d, J = 1.2 Hz, 1 H, H-1), 5.61 (s, 1 H, C6H5CH),
7.27–7.50 (m, 10 H, C6H5CH2, C6H5CH).
13C NMR (100 MHz, CDCl3): d = 14.6, 28.0, 50.4, 66.4, 68.4, 73.0,
74.1, 79.6, 91.8, 101.6, 126.0 (2 C), 127.6 (2 C), 127.7, 128.2 (2 C),
128.3 (2 C), 128.9, 137.3, 138.1.
[a]D25 +98 (c 0.4, CHCl3).
1H NMR (400 MHz, CDCl3): d = 1.26 (t, J = 7.3 Hz, 3 H,
SCH2CH3), 2.06 (s, 3 H, OCOCH3), 2.62–2.68 (m, 2 H, SCH2CH3),
3.06 (dd, J = 4.3, 2.6 Hz, 1 H, H-2), 3.70 (dd, J = 9.0, 8.6 Hz, 1 H,
H-4), 3.94 (ddd, J = 9.0, 4.1, 2.3 Hz, 1 H, H-5), 4.06 (dd, J = 8.4,
4.3 Hz, 1 H, H-3), 4.28 (dd, J = 12.1, 4.7 Hz, 1 H, H-6a), 4.32 (dd,
J = 11.9, 2.7 Hz, 1 H, H-6b), 4.55 (d, J = 11.0 Hz, 1 H), 4.63 (d,
J = 11.4 Hz, 1 H), 4.69 (d, J = 11.5 Hz, 1 H), 4.86 (d, J = 10.8 Hz,
1 H, 2 × C6H5CH2), 5.48 (d, J = 2.6 Hz, 1 H, H-1), 7.26–7.40 (m, 10
H, 2 × C6H5CH2).
MS (FAB+): m/z (%) = 428.2 [M+ + H].
13C NMR (100 MHz, CDCl3): d = 14.7, 20.8, 27.2, 48.6, 62.8, 72.3
(2 C), 74.2, 74.8, 78.3, 90.4, 127.9, 128.0, (3 C), 128.1 (2 C), 128.5
(2 C), 128.5 (2 C), 137.7, 137.8.
Anal. Calcd for C22H25N3O4S: C, 61.81; H, 5.89; N, 9.83; S, 7.50.
Found: C, 61.70; H, 5.96; N, 9.92; S, 7.34.
MS (FAB+): m/z (%) = 472 [M+ + H].
Ethyl 2-Azido-3,6-di-O-benzyl-2-deoxy-1-thio-b-D-mannopy-
ranoside (8) and Ethyl 6-O-Acetyl-2-azido-3,4-di-O-benzyl-2-
deoxy-1-thio-b-D-mannopyranoside (11)
Anal. Calcd for C24H29N3O5S: C, 61.13; H, 6.20; N, 8.91; S, 6.80.
Found: C, 61.07; H, 6.11; N, 8.77; S, 6.68.
Method A: A solution of AlCl3 (270 mg, 2.02 mmol) in 2 mL of
(Et2O) was added dropwise during 30 min to a stirred mixture of 7
(214 mg, 0.50 mmol), BH3–trimethylamine complex (370 mg, 5.07
mmol) and 4Å MS in CH2Cl2–Et2O (5:1, 8 mL) at 0 °C. After 1 h,
the mixture was filtered through celite and 1 M H2SO4 (10 mL) was
added to the filtrate, which was then stirred for 30 min. The organic
layer was washed with sat. aq NaHCO3 (10 mL), H2O (15 mL),
dried (MgSO4) and evaporated. Chromatography of the residue on
a silica gel column (10 g) with toluene–EtOAc (20:1) gave a mix-
ture of 8 and 2-azido-3,4-di-O-benzyl-2-deoxy-1-thio-b-D-man-
nopyranoside (198 mg, 92%), which was subjected to a selective
acetylation of the primary hydroxyl group before purification. The
above-mentioned mixture and sym-collidine (133 mL, 1.01 mmol)
Ethyl 4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-1-thio-b-D-
mannopyranoside (9)
To a stirred solution of compound 8 (735 mg, 1.71 mmol) in anhyd
pyridine (10 mL), Ac2O (2.0 mL, 21.16 mmol) was added. The re-
action mixture was stirred overnight at r.t. Progress of the reaction
was monitored using TLC with toluene–EtOAc (5:1). The mixture
was diluted with toluene (40 mL), washed with 1 M aq HCl (30
mL), sat. aq NaHCO3 (30 mL), H2O (2 × 30 mL), dried (MgSO4)
and evaporated. Chromatography of the residue on a silica gel col-
umn (15 g) in toluene–EtOAc (15:1) afforded 720 mg (89%) of
compound 9.
[a]D25 +77 (c 0.2, CHCl3).
Synthesis 2006, No. 4, 699–705 © Thieme Stuttgart · New York

704
J. Veselý et al.
PAPER
IR (CHCl3): 1744, 1234, 1044 (OAc), 2111, 1263, 566 (N3) cm–1.
H2O (50 mL), dried (MgSO4) and evaporated. The residue was pu-
rified on a silica gel column (25 g) in hexane–EtOAc (6:1) to yield
681 mg (79%) of compound 12.
[a]D25 +4 (c 0.5, CHCl3).
1H NMR (500 MHz, CDCl3): d = 1.30 (t, J = 7.4 Hz, 3 H,
SCH2CH3), 2.81 (q, J = 7.4 Hz, 2 H, SCH2CH3), 3.17 (dd, J = 4.2,
2.0 Hz, 1 H, H-2), 3.47 (dt, J = 10.0, 10.0, 4.9 Hz, 1 H, H-5), 3.74
(t, J = 10.4 Hz, 1 H, H-6a), 3.93 (dd, J = 9.6, 4.2 Hz, 1 H, H-3), 4.04
(t, J = 9.8 Hz, 1 H, H-4), 4.30 (dd, J = 10.4, 4.9 Hz, 1 H, H-6b), 4.68
(d, J = 12.0 Hz, 1 H, CH2CCl3), 4.77 (d, J = 12.3 Hz, 1 H,
C6H5CH2), 4.82 (d, J = 12.0 Hz, 1 H, CH2CCl3), 4.91 (d, J = 12.3
Hz, 1 H, C6H5CH2), 5.26 (dd, J = 10.1, 2.0 Hz, 1 H, H-1), 5.60 (s, 1
H, C6H5CH), 6.62 (br d, J = 10.1 Hz, 1 H, NH), 7.27–7.51 (m, 10 H,
2 × Ph).
1H NMR (400 MHz, CDCl3): d = 1.23 (t, J = 7.5 Hz, 3 H,
SCH2CH3), 1.96 (s, 3 H, OAc), 2.66 (q, J = 7.5 Hz, 2 H, SCH2CH3),
3.00 (t, J = 4.1 Hz, 1 H, H-2), 3.58 (dd, J = 10.8, 4.0 Hz, 1 H, H-6a),
3.63 (dd, J = 10.8, 5.8 Hz, 1 H, H-6b), 3.92 (dd, J = 7.2, 4.0 Hz, 1
H, H-3), 4.03 (ddd, J = 8.1, 5.8, 3.8 Hz, 1 H, H-5), 4.51 (d, J = 11.9
Hz, 1 H), 4.55 (d, J = 11.9 Hz, 1 H), 4.57 (d, J = 11.9 Hz, 1 H), 4.63
(d, J = 12.1 Hz, 1 H, 2 × C6H5CH2), 5.21 (dd, J = 8.1, 7.3 Hz, 1 H,
H-4), 5.45 (d, J = 4.1 Hz, 1 H, H-1), 7.24–7.36 (m, 10 H, 2 ×
C6H5CH2).
13C NMR (100 MHz, CDCl3): d = 14.6, 20.9, 27.1, 47.9, 68.3, 68.9,
72.1, 72.8, 73.4, 76.4, 90.0, 127.6, 127.7 (4 C), 127.8, 128.3 (4 C),
137.5, 137.8, 169.6.
MS (FAB+): m/z (%) = 472 [M+ + H].
13C NMR (125 MHz, CDCl3): d = 14.8, 28.6, 53.2, 68.4, 69.3, 73.3,
74.8, 77.8, 78.0, 80.0, 95.0, 101.5, 126.0, 127.7, 127.9, 128.2 (2 C),
128.5 (2 C), 128.9, 137.3, 138.1, 153.5.
Anal. Calcd for C24H29N3O5S: C, 61.13; H, 6.20; N, 8.91; S, 6.80.
Found: C, 61.02; H, 6.19; N, 8.87; S, 6.67.
Ethyl 4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-1-thio-b-D-
mannopyranoside S-Oxide (10)
MS (FAB+): m/z (%) = 576 [M+ + H].
Anal. Calcd for C25H28Cl3NO6S: C, 52.05; H, 4.89; Cl, 18,44; N,
2.43; S, 5.56. Found: C, 51.96; H, 4.95; Cl, 18,31; N, 2.37; S, 5.44.
To a stirred solution of compound 9 (92 mg, 0.20 mmol) in anhyd
CH2Cl2 (4 mL), MCPBA (38 mg, 0.22 mmol) was added at –30 °C.
The reaction mixture was warmed to –10 °C and stirred for 1 h.
Progress of the reaction was monitored using TLC with toluene–
EtOAc (2:1). After the reaction was quenched with sat. aq NaHCO3
(6 mL), CH2Cl2 was added (10 mL). Reaction mixture was warmed
to r.t., washed with H2O (6 mL), dried (MgSO4) and evaporated.
The residue was purified on a silica gel column (7 g) with toluene–
EtOAc (2:1) to yield 77 mg (81%) of compound 10.
4-O-Acetyl-3,6-di-O-benzyl-2-S-ethyl-2-thio-b-D-mannopy-
ranosyl-(2,2,2-trichloroethoxycarbonyl)amine (13)
To a stirred mixture of compound 9 (470 mg, 1.00 mmol) in pyri-
dine–H2O (9:1, 30 mL) at r.t., 1,3-propanedithiole (1.4 mL, 13.94
mmol) and Et3N (1.4 mL, 10.04 mmol) were added. The reaction
mixture was stirred overnight at r.t. Progress of the reaction was
monitored using TLC with toluene–EtOAc (5:1). The mixture was
diluted with toluene (60 mL), washed with 1 M aq HCl (60 mL), sat.
aq NaHCO3 (60 mL), H2O (60 mL), dried (MgSO4) and evaporated.
The residue was purified on a silica gel column (20 g) with toluene–
CHCl3 (1:4) to yield a solid residue (330 mg), which was dissolved
in anhyd pyridine (20 mL). TrocCl (1.8 mL, 13.07 mmol) was add-
ed at 0 °C, the reaction mixture was warmed to r.t. and stirred for 2
h. Progress of the reaction was monitored using TLC with toluene–
EtOAc (5:1). The mixture was diluted with toluene (60 mL),
washed with 1 M aq HCl (2 × 30 mL), sat. aq NaHCO3 (30 mL),
H2O (30 mL), dried (MgSO4) and evaporated. The residue was pu-
rified on a silica gel column (20 g) with hexane–EtOAc (6:1) to
yield 390 mg (63%) of compound 13.
[a]D25 +81 (c 0.2, CHCl3).
IR (CHCl3): 1045 (S=O), 1749, 1233, 1021 (OAc), 2115, 1260, 564
(N3) cm–1.
1H NMR (500 MHz, CDCl3): d = 1.32 (t, J = 7.4 Hz, 3 H,
SCH2CH3), 1.88 (s, 3 H, OAc), 2.71 (dq, J = 13.2, 7.4, 7.4, 7.4 Hz,
1 H, SCH2CH3), 3.06 (dq, J = 13.2, 7.4, 7.4, 7.4 Hz, 1 H,
SCH2CH3), 3.23 (dd, J = 4.5, 2.2 Hz, 1 H, H-2), 3.60 (dd, J = 10.9,
3.7 Hz, 1 H, H-6a), 3.64 (dd, J = 10.9, 5.2 Hz, 1 H, H-6b), 4.09 (dd,
J = 9.2, 4.9 Hz, 1 H, H-3), 4.09 (ddd, J = 9.4, 5.2, 3.7 Hz, 1 H, H-
5), 4.53 (d, J = 11.7 Hz, 1 H), 4.55 (s, 2 H), 4.57 (d, J = 11.7 Hz, 1
H, 2 × C6H5CH2), 5.33 (dd, J = 9.2, 4.9 Hz, 1 H, H-4), 5.94 (d,
J = 2.2 Hz, 1 H, H-1), 7.23–7.36 (m, 10 H, 2 × C6H5CH2).
[a]D25 –7 (c 0.7, CHCl3).
13C NMR (125 MHz, CDCl3): d = 6.6, 20.8, 47.1, 62.3, 68.8, 69.4,
72.3, 73.4, 73.7, 74.9, 85.5, 127.6, 127.8 (2 C), 127.9 (2 C), 128.3
(3 C), 128.6 (2 C), 136.5, 137.8, 169.5.
1H NMR (500 MHz, CDCl3): d = 1.25 (t, J = 7.3 Hz, 3 H,
SCH2CH3), 1.91 (s, 3 H, COCH3), 2.63 (dq, J = 12.3, 7.3, 7.3, 7.3
Hz, 1 H, SCH2CH3), 2.74 (dq, J = 12.3, 7.3, 7.3, 7.3 Hz, 1 H,
SCH2CH3), 3.19 (dd, J = 4.1, 1.9 Hz, 1 H, H-2), 3.49 (dd, J = 10.8,
5.1 Hz, 1 H, H-6a), 3.53 (dd, J = 10.8, 3.5 Hz, 1 H, H-6b), 3.59 (ddd,
J = 9.0, 5.1, 3.5 Hz, 1 H, H-5), 3.79 (dd, J = 9.1, 4.1 Hz, 1 H, H-3),
4.47 (d, J = 11.9 Hz, 1 H, C6H5CH2), 4.50 (d, J = 11.9 Hz, 1 H,
C6H5CH2), 4.54 (d, J = 12.1 Hz, 1 H, C6H5CH2), 4.67 (d, J = 12.1
Hz, 1 H, C6H5CH2), 4.68 (d, J = 11.9 Hz, 1 H, CH2CCl3), 4.81 (d,
J = 11.9 Hz, 1 H, CH2CCl3), 5.20 (dd, J = 10.0, 1.9 Hz, 1 H, H-1),
5.28 (t, J = 9.2 Hz, 1 H, H-4), 6.56 (d, J = 10.0 Hz, 1 H, NH), 7.23–
7.38 (m, 10 H, 2 × Ph).
MS (FAB+): m/z (%) = 488.2 [M+ + H].
Anal. Calcd for C24H29N3O6S: C, 59.12; H, 6.00; N, 8.62; S, 6.58.
Found: C, 59.16; H, 6.09; N, 8.52; S, 6.47.
3-O-Benzyl-4,6-O-benzylidene-2-S-ethyl-2-thio-b-D-mannopy-
ranosyl-(2,2,2-trichloroethoxycarbonyl)amine (12)
To a stirred solution of compound 7 (640 mg, 1.50 mmol) in pyri-
dine–H2O (9:1, 40 mL) at r.t., 1,3-propanedithiol (2 mL, 19.92
mmol) and Et3N (2 mL, 14.35 mmol) were added. The reaction mix-
ture was stirred overnight. Progress of the reaction was monitored
using TLC with toluene–EtOAc (5:1). The mixture was diluted with
toluene (100 mL), washed with 1 M aq HCl (100 mL), sat. aq
NaHCO3 (100 mL), H2O (100 mL), dried (MgSO4) and evaporated.
The residue was purified on a silica gel column (25 g) in toluene–
CHCl3 (1:4) to yield a solid residue (410 mg), which was dissolved
in anhyd pyridine (25 mL). TrocCl (2.4 mL, 17.43 mmol) was add-
ed at 0 °C, the reaction mixture was warmed to r.t. and stirred for 2
h. Progress of the reaction was monitored using TLC with toluene–
EtOAc (5:1). The mixture was diluted with toluene (100 mL),
washed with 1 M aq HCl (2 × 50 mL), sat. aq NaHCO3 (50 mL),
13C NMR (125 MHz, CDCl3): d = 14.8, 20.9, 27.8, 51.0, 68.8, 69.3,
72.2, 73.5, 74.7, 75.6, 79.3, 79.6, 95.1, 127.6, 127.7 (2 C), 127.9 (2
C), 128.0, 128.3 (2 C), 128.5 (2 C), 137.5, 137.8, 153.5, 169.6.
MS (FAB+): m/z (%) = 620 [M+ + H].
Anal. Calcd for C27H32Cl3NO7S: C, 52.22; H, 5.19; Cl, 17.13; N,
2.26; S, 5.16. Found: C, 52.18; H, 5.09; Cl, 17.01; N, 2.14; S, 5.11.
4-O-Acetyl-3,6-di-O-benzyl-2-S-ethyl-2-thio-b-D-mannopy-
ranosylamine (14)
[a]D25 –20 (c 0.1, CHCl3).
Synthesis 2006, No. 4, 699–705 © Thieme Stuttgart · New York

PAPER
Rearrangement of Ethylsulfanyl Group from C(1) to C(2) on Sugar Units
705
IR (CHCl3): 3397 (NH2), 1742, 1237, 1047 (OAc), 3090, 3067,
3032, 1497, 1455 (PhCH2) cm–1.
(14) Krist, P.; Herkommerová-Rajnochová, E.; Rauvolfová, J.;
Semeꢀuk, T.; Vavrušková, P.; Pavlíček, J.; Bezouška, K.;
Petrus, L.; Kꢁen, V. Biochem. Biophys. Res. Commun. 2001,
287, 11.
1H NMR (500 MHz, CDCl3): d = 1.26 (t, J = 7.4 Hz, 3 H,
SCH2CH3), 1.89 (s, 3 H, COCH3), 2.66 (dq, J = 12.0, 7.4, 7.4, 7.4
Hz, 1 H, SCH2CH3), 2.76 (dq, J = 12.0, 7.4, 7.4, 7.4 Hz, 1 H,
SCH2CH3), 3.38 (dd, J = 4.2, 1.6 Hz, 1 H, H-2), 3.44 (ddd, J = 9.5,
6.2, 3.2 Hz, 1 H, H-5), 3.46 (dd, J = 11.0, 3.2 Hz, 1 H, H-6a), 3.51
(dd, J = 11.0, 6.2 Hz, 1 H, H-6b), 3.66 (dd, J = 9.5, 4.2 Hz, 1 H, H-
3), 4.41 (d, J = 12.3 Hz, 1 H, C6H5CH2), 4.45 (dt, J = 9.8, 9.8, 1.6
Hz, 1 H, H-1), 4.47 (d, J = 11.9 Hz, 1 H, C6H5CH2), 4.50 (d,
J = 11.9 Hz, 1 H, C6H5CH2), 4.61 (d, J = 12.3 Hz, 1 H, C6H5CH2),
4.76 (br d, J = 9.8 Hz, 2 H, NH2), 5.12 (t, J = 9.5 Hz, 1 H, H-4),
7.25–7.39 (m, 10 H, 2 × C6H5CH2).
(15) Gattuso, G.; Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev.
1998, 98, 1919.
(16) Ennis, S. C.; Gridley, J. J.; Osborn, H. M. I.; Spackman, D.
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(17) Kaji, E.; Lichtenthaler, F. W.; Nishino, T.; Yamane, A.; Zen,
S. Bull. Chem. Soc. Jpn. 1988, 61, 1291.
(18) Kaji, E.; Osa, Y.; Takahashi, K.; Hirooka, M.; Zen, S.;
Lichtenthaler, F. W. Bull. Chem. Soc. Jpn. 1994, 67, 1130.
(19) Sato, K. I.; Yoshimoto, A. Chem. Lett. 1995, 24, 39.
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(21) Sugawara, T.; Irie, K.; Iwasawa, H.; Yoshikawa, T.; Okuno,
S.; Watanabe, H. K.; Kato, T.; Shibukawa, M.; Ito, Y.
Carbohydr. Res. 1992, 230, 117.
(22) Litjens, R. E. J. N.; Leeuwenburgh, M. A.; van der Marel, G.
A.; van Boom, J. H. Tetrahedron Lett. 2001, 42, 8693.
(23) Litjens, R. E. J. N.; van den Bos, L. J.; Codee, J. D. C.; van
den Berg, R. J. B. H.; Overkleeft, H. S.; van der Marel, G. A.
Eur. J. Org. Chem. 2005, 918.
13C NMR (125 MHz, CDCl3): d = 15.0, 20.9, 28.1, 52.8, 69.7, 70.4,
71.6, 73.5, 75.1, 79.8, 85.7, 127.6, 127.7 (2 C), 127.8 (2 C), 127.8,
128.3 (2 C), 128.4 (2 C), 137.3, 137.4, 169.8.
MS (FAB+): m/z (%) = 429 [M+ – NH3 + H].
Anal. Calcd for C24H31NO5S: C, 64.69; H, 7.01; N, 3.14; S, 7.20.
Found: C, 64.84; H, 7.11; N, 3.31; S, 7.07.
(24) Halcomb, R. L.; Fitz, W.; Wong, C. H. Tetrahedron:
Asymmetry 1994, 5, 2437.
Acknowledgment
We are thankful for the support to The Grant Agency of Charles
University in Prague (grant No. 416/2004 and grant No. 418/2004),
The Ministry of Agriculture (grant No. QF3115/2003) and the re-
search project No. Z4 055 0506.
(25) Yu, Y.; Ko, K. S.; Zea, C. J.; Pohl, N. L. Org. Lett. 2004, 6,
2031.
(26) Freese, S. J.; Vann, W. F. Carbohydr. Res. 1996, 281, 313.
(27) Alper, P. B.; Hung, S. C.; Wong, C. H. Tetrahedron Lett.
1996, 37, 6029.
(28) Buskas, T.; Garegg, P. J.; Konradsson, P.; Maloisel, J. L.
Tetrahedron: Asymmetry 1994, 5, 2187.
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Synthesis 2006, No. 4, 699–705 © Thieme Stuttgart · New York