Synthesis of a new type of D-mannosamine glycosyl donor and acceptor and their use for the preparation of oligosaccharides consisting of D-mannosamine units linked by α(1→4)-glycosidic bonds

Article abstract of DOI:10.1055/s-2008-1067197

Herein, we present the synthesis of three new 2-azido-2-deoxy-D- mannopyranose building blocks that are useful in the preparation of oligosaccharides consisting of α(1→4)-linked 2-azido-2-deoxy-D- mannopyranose units. The successful utilization of these i

Full text of DOI:10.1055/s-2008-1067197

2610
PAPER
Synthesis of a New Type of D-Mannosamine Glycosyl Donor and Acceptor
and their Use for the Preparation of Oligosaccharides Consisting of
D-Mannosamine Units Linked by a(1→4)-Glycosidic Bonds
a
(1
→
4)-LinkedOligos
a
accharide
s
tof the
y
-Mannosam
á
ine
T
ype š Turský,a,b,1 Jan Veselý,a Iva Tišlerová,a Tomáš Trnka,a Miroslav Ledvina*b
a
b
Fax +420(2)20183560; E-mail: ledvina@uochb.cas.cz
Received 1 February 2008; revised 6 May 2008
electronic effects of C(4) and C(6) substituents on the ste-
reochemical outcome of glycosylation was recently re-
ported.13
Abstract: Herein, we present the synthesis of three new 2-azido-2-
deoxy-D-mannopyranose building blocks that are useful in the prep-
aration of oligosaccharides consisting of a(1→4)-linked 2-azido-2-
deoxy-D-mannopyranose units. The successful utilization of these
intermediates in the stepwise synthesis of the corresponding trisac-
charide is also described in detail.
In 2006, we reported15 the synthesis of ethyl 2-azido-2-
deoxy-1-thio-b-D-mannopyranosides as potential build-
ing blocks for the preparation of oligosaccharides requir-
ing (1→4)-linked 2-azido-2-deoxy-D-mannopyranose
units. We demonstrated that the electronic interaction be-
tween the axially oriented azido group at C(2) and the
equatorial sulfur at atom C(1) on the activated mannopyr-
anoside led to significant deactivation of the alkylsulfanyl
moiety as the desired leaving group. Attempts to trans-
form the azido group into another suitably protected ami-
no functionality (trichloroethoxycarbonylamino or
phthalimido group) via its reduction into an amine were
also unsuccessful. Unfortunately, we found that azide re-
duction was followed by a positional ‘switch’ of substitu-
ents at C(1) and at C(2) with retention of configuration at
each position, to give 2-(S)-ethyl-2-thio-b-D-mannopyra-
nosylamines.
Key words: carbohydrates, glycosylation, oligosaccharides,
D-mannosamine
D-Hexopyranoses containing a 1,2-trans-(1→4)-linked 2-
amino-2-deoxy-sugar motif are common functionalities in
biologically important oligosaccharides and their glyco-
conjugates. This trans arrangement imparts multiple bio-
logical functions and activities.2,3 Due to their biological
significance, considerable efforts have been undertaken to
enable an efficient synthetic approach to these oligosac-
charides.4,5 In contrast to the large amount of work devot-
ed to the synthesis of homooligosaccharides with 1,2-
trans-b(1→4)-glycosidic linkages such as 2-amino-2-
deoxy-D-glucopyranose and 2-amino-2-deoxy-D-galacto-
pyranose units, to our knowledge, the synthesis of analo-
Herein we describe the synthesis of new D-mannosamine
building blocks with either the trichloroacetimidate or hy-
droxy functionality at C(1) as a leaving group and an azide
group at C(2). We also present the successful utilization of
these building blocks in the convergent synthesis of trisac-
charide 12, consisting of a(1→4)-linked 2-azido-2-
deoxy-D-mannopyranose units. The trichloroacet-
imidate16 as well as dehydrative17 methods were em-
ployed in parallel.
gous oligosaccharides with
a
1,2-trans-a(1→4)-
glycosidic linkage have received little attention.4–7 The
1,2-cis- as well as 1,2-trans-glycosidically (a- or b-)
linked 2-acetamido-2-deoxy-D-mannopyranose units are
the building blocks of numerous bacterial lipo- and capsu-
lar polysaccharides.8–10 Due to the biological importance,
considerable effort has been devoted to developing effi-
cient methods for the incorporation of the D-mannosamine
motif into various oligosaccharide chains. One approach,
based on mannoazidopyranoside having a non-participat-
ing C(2)-azido group within the glycosyl donor, is now
under intense study. This approach incorporates a masked
amino functionality and stereoselection of the glycosida-
tion reaction can be effectively controlled by steric and
electronic substituent effects.11–13 The 4,6-O-benzylidene-
protected donors generally afford b-glycosides, and thus
offers an improvement on existing methods.11,12 While
initially explained by torsional strain,14 the significance of
The synthetic pathway for the preparation of building
blocks 6, 8 and 9 started with known allyl 3-O-benzyl-4,6-
O-benzylidene-a-D-glucopyranoside (3), which was ob-
tained from D-glucose in three steps by a modified litera-
ture procedure (the described18 one-pot synthesis of 2 led
to an anomeric mixture of allyl 4,6-O-benzylidene-D-glu-
copyranosides that was difficult to separate by described
methods). Refluxing a suspension of D-glucose in allyl al-
cohol catalyzed by BF3·OEt2 gave crystalline allyl a-D-
glucopyranoside 1 in 16% yield. The benzylidene acetal 2
was formed with benzaldehyde in the presence of triethyl
orthoformate and trifluoromethanesulfonic acid in a mix-
ture of N,N-dimethylformamide and dioxane in 39%
yield. Regioselective 3-O-benzylation was accomplished
under modified (cesium fluoride) stannylene chemistry, to
SYNTHESIS 2008, No. 16, pp 2610–2616
x
x.
x
x
.
2
0
0
8
Advanced online publication: 25.07.2008
DOI: 10.1055/s-2008-1067197; Art ID: T01808SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
a(1→4)-Linked Oligosaccharides of the D-Mannosamine Type
2611
HO
HO
HO
pylethylamine (DIPEA) and N,N-dimethylaminopyridine
(DMAP).
HO
Ph
Ph
O
i
ii
O
O
O
O
HO
HO
16%
39%
HO
OH
OH
OH
OH
D-Glc
Our attempts to invert the configuration at C(2) of mesy-
late 4a by nucleophilic attack with lithium azide in hot
N,N-dimethylformamide were unsuccessful, while the re-
action of triflate 4b and nonaflate 4c under identical con-
ditions gave key intermediate 5 in 78% and 86% yield,
respectively (Scheme 1). Glycosyl acceptor 6 was pre-
pared from compound 5 by reductive cleavage of the ben-
zylidene acetal group with triethylsilane in the presence of
trifluoroacetic acid (TFA) in 68% yield. Formation of the
4-O-benzyl ether was not observed.
OAll
OAll
1
2
iii
40%
Ph
O
O
O
O
O
O
iv (X = Ms; 95%)
v (X = Tf; 89%)
vi (X = Nf; 86%)
BnO
BnO
4a X = Ms
4b X = Tf
4c X = Nf
OX
OH
3
OAll
OAll
X = Ms; 0%
X = Tf; 78%
X = Nf; 86%
vii
N3
O
Ph
O
O
BnO
The reaction of 6 with acetic anhydride in pyridine gave
the 4-O-acetate 7 in 82% yield. The anomeric allyl protec-
tive group was removed using a cleavage protocol, form-
ing 1-propenyl ether using a catalytic amount of
palladium(II) chloride in a methanol–ethanol mixture,
yielding the glycosyl donor 8 in 87% yield. Transforma-
tion of the anomeric hydroxy group into a trichloroacetim-
idate [TCAI; Cl3CC(NH)-] on treatment with
trichloroacetonitrile in the presence of 1,8-diazabicyc-
lo[5.4.0]undec-7-ene (DBU; 0.3 equiv) in dichloro-
5
OAll
Scheme 1 Synthesis of azido derivative 5. Reagents and conditions:
(i) AllOH, BF3·OEt2; (ii) PhCHO, (EtO)3CH, TfOH, DMF–dioxane;
(iii) Bu2SnO, MeOH, then BnBr, CsF, DMF; (iv) MsCl, py; (v) Tf2O,
py, CH2Cl2; (vi) NfF, DIPEA, DMAP, CH2Cl2; (vii) LiN3, DMF.
N3
BnO
HO
N3
BnO
AcO
N3
Ph
O
i
ii
O
O
O
O
68%
82%
BnO
BnO
BnO
5
6
7
OAll
OAll
OAll
87%
methane, afforded the a-trichloroacetimidate
exclusively in 70% yield (Scheme 2).
9
iii
N3
BnO
AcO
BnO
AcO
N3
O
iv
O
Glycosylation was performed utilizing the trichloroace-
timidate protocol or the dehydrative method. The reaction
of acceptor 6 with the trichloroacetimidate 9 in dichlo-
romethane in the presence of trimethylsilyl trifluo-
romethanesulfonate (TMSOTf; 1.1 equiv) gave the a-
glycoside 10 in 60% yield. Using the dehydrative method
(donor 8, activation Ph2SO, Tf2O, TTBP; TTBP = 2,4,6-
70%
BnO
BnO
8
9
OH
OTCAI
Scheme 2 Synthesis of glycosyl donors. Reagents and conditions:
(i) Et3SiH, TFA, CH2Cl2; (ii) Ac2O, py; (iii) PdCl2 (cat.), EtOH–
MeOH; (iv) Cl3CCN, DBU, CH2Cl2.
give 3 in 40% yield. Under these conditions, methyl 4,6- tri-tert-butyl pyrimidine), the a-linked disaccharide 10
O-benzylidene-a-D-mannopyranoside yielded the 3-O- was isolated in 78% yield. No formation of the b-glyco-
benzyl derivative preferentially.19
side was detected in either case (Scheme 3). The trisac-
charide 12 was prepared in a similar manner from
disaccharide 10 by a route involving Zemplén deacetyl-
ation of 10 to give 11 and subsequent glycosylation of 11
to give 12 (trichloroacetimidate method, 40% yield; dehy-
drative method, 65% yield), as shown in Scheme 4.
For the synthesis of the key intermediate allyl 2-azido-2-
deoxy-3-O-benzyl-4,6-O-benzylidene-a-D-mannopyrano-
side (5), three sulfonates were prepared. The reaction of 3
with methanesulfonyl chloride in pyridine gave the crys-
talline 2-O-mesyl derivative 4a in 95% yield. The trifluo-
romethanesulfonyl derivative 4b was prepared by the The anomeric configuration of disaccharide 10 and trisac-
reaction of 3 with triflic anhydride in a mixture of dichlo- charide 12 were confirmed by NMR spectroscopy. In the
romethane and pyridine with 89% yield. The nonafluoro- 2D-ROESY spectra, cross-peaks between hydrogens H-1
butanesulfonyl derivative 4c was obtained in 86% yield by (H-1¢, H-1¢¢) and H-3 (H-3¢, H-3¢¢) and/or H-5 (H-5¢, H-
the reaction of 3 with nonafluorobutanesulfonyl fluoride 5¢¢) are absent. These cross-peaks are typical for b-config-
(NfF) in dichloromethane in the presence of N,N-diisopro- uration, where H-1, H-3 and H-5 are syn-axial and thus
BnO
AcO
N3
O
BnO
HO
N3
O
+
BnO
BnO
i
OTCAI
OAll
N3
O
BnO
AcO
9
6
BnO
BnO
N3
O
ii
O
10
BnO
BnO
HO
N3
O
BnO
AcO
N3
O
+
OAll
BnO
BnO
OH
OAll
8
6
Scheme 3 Glycosylation with donors 9 and 8. Reagents and conditions: (i) TMSOTf, CH2Cl2; (ii) donor activation: Ph2SO, TTBP, Tf2O, then
glycosylation: solution of acceptor in CH2Cl2.
Synthesis 2008, No. 16, 2610–2616 © Thieme Stuttgart · New York

2612
M. Turský et al.
PAPER
BnO
AcO
BnO
BnO
HO
N3
N3
O
O
i
BnO
BnO
N3
O
N3
O
BnO
82%
O
O
BnO
BnO
10
11
OAll
OAll
N3
O
BnO
AcO
BnO
BnO
AcO
N3
O
ii
11
+
40%
BnO
BnO
N3
O
OTCAI
O
BnO
BnO
N3
O
9
12
O
BnO
BnO
AcO
N3
iii
O
11
12
+
OAll
65%
BnO
OH
8
Scheme 4 Synthesis of trisaccharide 12. Reagents and conditions: (i) MeONa, MeOH; (ii) TMSOTf, CH2Cl2; (iii) donor activation: Ph2SO,
TTBP, Tf2O, then glycosylation: solution of acceptor in CH2Cl2.
spatially close. Furthermore, 3J(H–C–C–C) coupling con-
stants can be estimated from the intensity of cross-peaks
FAB mass spectra were obtained using a ZAB-EQ sector mass
spectrometer (VG Analytical, Manchester) equipped with a Xe gas
FAB gun. The instrument was controlled by OPUS running on
in 2D-H,C-HMBC spectra. We observed strong cross
AlfaStation in the Open VMS environment. Optical rotations were
peaks between hydrogen H-1 and carbons C-3 and C-5 in-
determined on an Autopol IV (Rudolph Research Analytical, USA)
dicating an antiparallel arrangement of these atoms, which
polarimeter at 589 nm at 20 °C and [a]D values are given in
deg·cm2·g–1. Elemental analysis (C, H, N) were performed on a PE
2400 Series II CHNS/O Analyzer (Perkin–Elmer, USA), halogens
and sulfur were determined by titration methods. IR spectra were
measured on a Bruker IFS-55 instrument as CHCl3 solutions and
wavenumbers are given in cm–1 (only structurally important peaks
are given). Melting points were determined on a Boëtius microap-
paratus and are uncorrected. TLC were performed on Merck silica
gel 60 F254 sheets with UV or carbonization detection. For column
chromatography, Fluka silica gel 60 (230–400 mesh) was used. Sol-
vents were dried and distilled from P2O5 (DMF, CH2Cl2), Mg
(MeOH), KOH (pyridine) or Na (dioxane) and were stored over 4 Å
MS. Glucose was dried over P2O5 under reduced pressure. For gly-
cosylations, powdered 4 Å MS (Fluka) were used. Lithium azide
was prepared according to the literature procedure.22
is possible only in the case of the a-anomer. For compar-
ison, cross peaks between H-4 and C-2 and C-6 had much
lower intensity. These atoms are in gauche arrangement.
In summary, the synthesis of 2-azido-2-deoxy-D-man-
nopyranosyl donors and acceptors suitable for the prepa-
ration of D-mannosamine type a(1→4)-linked
oligosaccharides as well as a synthetic procedure for the
build-up of the oligosaccharide chain have been devel-
oped. A combination of the influence of the electron-with-
drawing character of the azido group at C(2) of glycosyl
donor and a low reactivity of the OH(4) group of glycosyl
acceptor, resulted in preferential formation of the a-glyco-
sidic bond. As previously stated, it is well known that the
electron-withdrawing effect of the azido group at C(2) of
the glycosyl donor significantly modulates the course and
facial selectivity of the glycosylation reaction, regardless
of which protocol we used. Furthermore, it has been sug-
gested that decreased reactivity of glycosyl acceptors
leads preferentially to a-mannosides, and the present
work supports this hypothesis.12,20 These results lead the
way to the synthesis of oligosaccharides having a(1→4)-
linked D-mannosamine units which are of significant syn-
thetic and biological interest. Possessing axial glycosidic
linkages to equatorial C(4)–O bonds, the described oli-
gosaccharides satisfy the basic criteria for cyclization,
which should lead to the formation of 2-amino-2-deoxy-
cyclomannin analogues of cyclodextrins.21 Synthesis of
these cyclodextrin analogues will be reported in due
course.
Allyl a-D-Glucopyranoside (1)
Dried D-glucose (80.23 g, 445.32 mmol) was refluxed in allyl alco-
hol (470 mL) with BF3·OEt2 (6 mL) for 4 h, then the mixture was
cooled to r.t., quenched with Et3N (50 mL), the solvent was evapo-
rated and the residue was recrystallized from EtOAc (2 × 500 mL)
to give the title compound 1.
Yield: 15.85 g (16%); white solid; mp 97–98 °C (EtOAc) [Lit.23 99–
100 °C (EtOAc–EtOH, 1:1)]; [a]D +141 (c 0.3, H2O) [Lit.23 +140.6
(c 1.4, H2O)].
1H NMR (400 MHz, D2O): d = 5.99 (dddd, J = 5.5, 6.2, 10.4, 17.3
Hz, 1 H), 5.38 (qd, J = 1.6, 17.3 Hz, 1 H), 5.27 (tdd, J = 1.2, 1.7,
10.4 Hz, 1 H), 4.97 (d, J = 3.8 Hz, 1 H), 4.27–4.21 (m, 1 H), 4.11–
4.05 (m, 1 H), 3.88–3.67 (m, 4 H), 3.57 (dd, J = 3.8, 9.8 Hz, 1 H),
3.41 (dd, J = 9.1, 9.9 Hz, 1 H). 1H NMR is in agreement with liter-
ature.24
Allyl 4,6-O-Benzylidene-a-D-glucopyranoside (2)
The glycoside 1 (76.91 g, 349.2 mmol) was dissolved in anhyd
DMF–dioxane (1:1, 600 mL), triethyl orthoformate (180 mL, 1.08
mol), benzaldehyde (135 mL, 1.33 mol) and TfOH (4.5 mL, 50.8
mmol) were added and the mixture was stirred at r.t. for 3 d, poured
into ice-cold sat. aq NaHCO3 (300 mL) and diluted with H2O (1.5
L). The crude crystals were filtered off and recrystallized from
MeOH (0.5 L) to yield 2.
NMR spectra were recorded on Bruker AVANCE-500, Bruker
AVANCE-400 or Varian UNITY INOVA 400 instruments (1H
NMR at 500 or 400 MHz, respectively; 13C NMR at 125 or 100
MHz, respectively) as CDCl3 or D2O solutions (referenced to TMS
or solvent central peak); data are given as d values in ppm. ESI MS
were measured on a LCQ Classic (Thermo Finnigan) instrument;
HR-ESI MS were measured on a Q-Tof micro (Waters) instrument.
Yield: 42.15 g (39%); mp 133–135 °C (CHCl3) [Lit.18 135–137 °C
(EtOAc)]; [a]D +114 (c 0.5, CHCl3) [Lit.18 +109.3 (c 1.01, CHCl3)].
Synthesis 2008, No. 16, 2610–2616 © Thieme Stuttgart · New York

PAPER
a(1→4)-Linked Oligosaccharides of the D-Mannosamine Type
2613
1H NMR (400 MHz, CDCl3): d = 7.52–7.46 (m, 2 H), 7.40–7.34 (m,
3 H), 5.93 (dddd, J = 5.4, 6.2, 10.4, 16.8 Hz, 1 H), 5.53 (s, 1 H),
5.33 (ddd, J = 1.4, 2.9, 17.2 Hz, 1 H), 5.25 (br dd, J = 1.2, 10.4 Hz,
1 H), 4.95 (d, J = 4.0 Hz, 1 H), 4.30–4.22 (m, 2 H), 4.10–4.02 (m,
1 H), 3.98–3.92 (m, 1 H), 3.98–3.92 (m, 1 H), 3.73 (t, J = 10.2 Hz,
1 H), 3.67–3.60 (m, 1 H), 3.52–3.46 (m, 2 H), 2.83 (br d, J = 1.6 Hz,
1 H), 2.31 (d, J = 9.6 Hz, 1 H). 1H NMR is in agreement with liter-
ature.18
Allyl 3-O-Benzyl-4,6-O-benzylidene-2-O-trifluormethanesulfo-
nyl-a-D-glucopyranoside (4b)
The benzyl ether 3 (3.61 g, 9.0 mmol) was dissolved in anhyd
CH2Cl2 (90 mL) and anhyd pyridine (3.8 mL) under an argon atmo-
sphere. The solution was cooled to –30 °C and Tf2O (2.3 mL, 13.6
mmol) was added dropwise. The mixture was stirred for 20 min at
–30 °C and then for 1 h at r.t., poured into ice-cold sat. aq NaHCO3
(150 mL) and extracted with CHCl3 (100 mL). The organic layer
was dried over MgSO4 and evaporated. Column chromatography on
silica gel (toluene) afforded the product 4b.
Allyl 3-O-Benzyl-4,6-O-benzylidene-a-D-glucopyranoside (3)
The benzylidene acetal 2 (57.05 g, 185 mmol) was refluxed with
Bu2SnO (64.91 g, 260.7 mmol) in MeOH (900 mL) until the solid
dissolved (1.5 h), then the solvent was evaporated to dryness and the
residue was dissolved in anhyd DMF (650 mL). CsF (34.53 g, 227.3
mmol) and BnBr (24 mL, 202 mmol) were added and the mixture
was stirred at r.t. overnight. The solvent was evaporated under re-
duced pressure and the residue was partitioned between brine (1 L)
and CHCl3 (5 × 200 mL). The combined organic layers were ex-
tracted with brine (500 mL), dried over MgSO4 and the solvent was
evaporated. The solid residue was crystallized (n-heptane–EtOH) to
afford the title compound 3.
Yield: 4.31 g (89%); white solid; [a]D +57 (c 0.4, CHCl3).
1H NMR (CDCl3, 400 MHz): d = 7.27–7.49 (m, 10 H, CHC6H5,
OCH2C6H5), 5.90 (dddd, J = 16.9, 10.2, 6.4, 5.2 Hz, 1 H,
OCH2CH=CH2), 5.57 (s, 1 H, CHC6H5), 5.35 (dq, J = 17.2, 1.5 Hz,
1 H, OCH2CH=CH2), 5.29 (dq, J = 10.4, 1.2 Hz, 1 H,
OCH2CH=CH2), 5.12 (d, J = 3.8 Hz, 1 H, H-1), 4.87 (d, J = 11.0
Hz, 1 H, OCH2C6H5), 4.77 (d, J = 11.0 Hz, 1 H, OCH2C6H5), 4.74
(dd, J = 9.5, 3.8 Hz, 1 H, H-2), 4.31 (dd, J = 10.4, 4.9 Hz, 1 H, H-
6b), 4.25 (ddt, J = 12.7, 5.3, 1.2 Hz, 1 H, OCH2CH=CH2), 4.17 (t,
J = 9.3 Hz, 1 H, H-3), 4.07 (ddt, J = 12.8, 6.6, 1.4 Hz, 1 H,
OCH2CH=CH2), 3.95 (td, J = 9.9, 4.9 Hz, 1 H, H-5), 3.75 (t,
J = 10.4 Hz, 1 H, H-6a), 3.70 (t, J = 9.5 Hz, 1 H, H-4).
13C NMR (CDCl3, 100 MHz): d = 137.32, 136.84, 132.50, 129.14,
128.31 (4 × C), 128.23 (2 × C), 127.91, 125.94 (2 × C), 119.03,
118.40 (q, J = 319 Hz, CF3SO2), 101.44, 95.48, 83.44, 82.03, 75.33,
75.09, 69.15, 68.61, 62.45.
MS (ESI): m/z [M + Na]+ calcd for C24H25F3NaO8S: 553.11; found:
553.1.
Yield: 29.95 g (40%); white crystals; mp 137–138 °C (CHCl3)
(Lit.25 135–136 °C); [a]D +87 (c 0.1, CHCl3) [Lit.25 +77.5 (c 1.11,
CHCl3)].
1H NMR (400 MHz, CDCl3): d = 7.53–7.47 (m, 2 H), 7.41–7.24 (m,
8 H), 5.93 (dddd, J = 5.5, 6.2, 10.4, 16.9 Hz, 1 H), 5.57 (s, 1 H),
5.32 (ddd, J = 1.5, 3.0, 17.2 Hz, 1 H), 5.24 (brdd, J = 1.3, 10.4 Hz,
1 H), 4.97 (d, J = 11.6 Hz, 1 H), 4.96 (d, J = 3.6 Hz, 1 H), 4.80 (d,
J = 11.6 Hz, 1 H), 4.31–4.20 (m, 2 H), 4.10–4.03 (m, 1 H), 3.92–
3.82 (m, 2 H), 3.78–3.72 (m, 2 H), 3.65 (t, J = 9.4 Hz, 1 H), 2.29 (d,
J = 8.0 Hz, 1 H). 1H NMR is in agreement with literature.26
Anal. Calcd for C24H25F3O8S: C, 54.34; H, 4.75; F, 10.74; S, 6.04.
Found: C, 54.26; H, 4.61; F, 10.38; S, 6.12.
Allyl 3-O-Benzyl-4,6-O-benzylidene-2-O-methanesulfonyl-a-D-
glucopyranoside (4a)
Allyl 3-O-Benzyl-4,6-O-benzylidene-2-(nonafluorobutanesulfo-
nyl)-a-D-mannopyranoside (4c)
The benzyl ether 3 (1.0 g, 2.5 mmol) was dissolved in anhyd pyri-
dine (10 mL) under an argon atmosphere and MsCl (0.7 mL, 9.3
mmol) was slowly added. The reaction mixture was stirred at r.t. for
24 h then toluene (60 mL) was added and the mixture was washed
with cool aq HCl (1M, 3 × 20 mL), H2O (3 × 20 mL), dried over
MgSO4 and evaporated. Crystallization of the residue from EtOH
(15 mL) afforded the product 4a.
NfF (1.1 mL, 6.2 mmol) was added dropwise to a solution of 3
(0.525 g, 1.31 mmol), DMAP (0.54 g, 4.4 mmol) and DIPEA (1 mL,
5.8 mmol) in anhyd CH2Cl2 (6 mL) under an argon atmosphere at
0 °C. The mixture was stirred at r.t. overnight then poured into sat.
aq NaHCO3 (40 mL) and extracted with CHCl3 (2 × 5 mL). The
combined organic layers were dried over MgSO4 and evaporated.
Column chromatography of the residue on silica gel (toluene–
EtOAc, 20:1) afforded 4c.
Yield: 1.14 g (95%); mp 105 °C; [a]D +42 (c 0.5, CHCl3).
1H NMR (CDCl3, 400 MHz): d = 7.27–7.49 (m, 10 H, CHC6H5,
OCH2C6H5), 5.94 (dddd, J = 16.5, 10.4, 6.1, 5.3 Hz, 1 H,
OCH2CH=CH2), 5.60 (s, 1 H, CHC6H5), 5.35 (dq, J = 17.2, 1.5 Hz,
1 H, OCH2CH=CH2), 5.26 (dq, J = 10.4, 1.2 Hz, 1 H,
OCH2CH=CH2), 5.10 (d, J = 3.8 Hz, 1 H, H-1), 4.98 (d, J = 11.0
Hz, 1 H, OCH2C6H5), 4.67 (d, J = 11.1 Hz, 1 H, OCH2C6H5), 4.48
(dd, J = 9.6, 3.8 Hz, 1 H, H-2), 4.31 (dd, J = 10.4, 4.9 Hz, 1 H, H-
6b), 4.24 (ddt, J = 12.8, 5.2, 1.5 Hz, 1 H, OCH2CH=CH2), 4.14 (t,
J = 9.5 Hz, 1 H, H-3), 4.11 (ddt, J = 13.0, 6.1, 1.2 Hz, 1 H,
OCH2CH=CH2), 3.96 (td, J = 10.1, 4.9 Hz, 1 H, H-5), 3.77 (t,
J = 10.4 Hz, 1 H, H-6a), 3.71 (t, J = 9.5 Hz, 1 H, H-4), 2.87 (s, 3 H,
OSO2CH3).
13C NMR (CDCl3, 100 MHz): d = 137.77, 136.99, 133.02, 129.08,
128.43 (2 × C), 128.29 (2 × C), 128.09 (2 × C), 127.97, 125.94 (2 ×
C), 118.45, 101.38, 96.76, 82.58, 78.76, 76.03, 75.33, 69.10, 68.80,
62.37, 38.07.
MS (ESI): m/z [M + Na]+ calcd for C24H28NaO8S: 499.14; found:
499.2.
Yield: 774 mg (86%); colorless oil; [a]D +42 (c 0.5, CHCl3).
1H NMR (500 MHz, CDCl3): d = 7.48–7.26 (m, 10 H, ArH), 5.90
(dddd, J = 5.4, 6.5, 10.3, 17.0 Hz, 1 H, OCH2CH=CH2), 5.57 (s,
1 H, PhCHO2), 5.34 (dq, J = 1.5, 17.0 Hz, 1 H, OCH2CH=CH2),
5.27 (ddt, J = 1.2, 1.4, 10.3 Hz, 1 H, OCH2CH=CH2), 5.12 (d,
J = 3.8 Hz, 1 H, H-1), 4.87 (d, J = 10.9 Hz, 1 H, CH2-Ph), 4.81 (dd,
J = 3.8, 9.5 Hz, 1 H, H-2), 4.78 (d, J = 10.9 Hz, 1 H, CH2-Ph), 4.31
(dd, J = 4.9, 10.3 Hz, 1 H, H-6a), 4.25 (ddt, J = 1.4, 5.4, 12.6 Hz,
1 H, OCH2CH=CH2), 4.18 (t, J = 9.4 Hz, 1 H, H-3), 3.95 (ddd,
J = 4.9, 9.7, 10.3 Hz, 1 H, H-5), 3.76 (t, J = 10.3 Hz, 1 H, H-6b),
3.71 (t, J = 9.5 Hz, 1 H, H-4).
13C NMR (100 MHz, CDCl3): d = 137.30, 136.86 (CAr), 132.47
(OCH2CH=CH2), 129.14, 128.31 (2 × C), 128.30 (2 × C), 128.25
(2 × C), 127.89, 125.95 (CAr), 119.01 (OCH2CH=CH2), 101.46
(CH-Ph), 95.51 (C-1), 83.58 (C-2), 82.09 (C-4), 75.35 (CH2-Ph),
75.22 (C-3), 69.22 (OCH2CH=CH2), 68.63 (C-6), 62.48 (C-5).
MS (ESI): m/z [M + Na]+ calcd for C27H25F9NaO8S: 703.10; found:
702.9.
Anal. Calcd for C24H28O8S: C, 60.49; H, 5.92; S, 6.73. Found: C,
60.27; H, 5.86; S, 6.78.
Anal. Calcd for C27H25F9O8S: C, 47.65; H, 3.70; F, 25.13; S, 4.71.
Found: C, 47.65; H, 3.59; F, 25.04; S, 4.88.
Synthesis 2008, No. 16, 2610–2616 © Thieme Stuttgart · New York

2614
M. Turský et al.
PAPER
Allyl 2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-a-D-man-
nopyranoside (5)
MS (ESI): m/z [M + Na]+ calcd for C23H27N3NaO5: 448.18; found:
448.2.
Method A: LiN3 (1.30 g, 26.5 mmol) and 4b (4.72 g, 8.9 mmol)
were dissolved in anhyd DMF (100 mL) under an argon atmosphere
and the solution was heated to 120 °C for 1 h. The solvent was evap-
orated under reduced pressure and the residue was partitioned be-
tween H2O (250 mL) and toluene (100 mL). The organic layer was
dried over MgSO4 and the solvent was evaporated. Column chro-
matography on silica gel (toluene) afforded the product 5.
Anal. Calcd for C23H27N3O5: C, 64.93; H, 6.40; N, 9.88. Found: C,
64.63; H, 6.38; N, 6.65.
Allyl 4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-manno-
pyranoside (7)
Ac2O (4.8 mL, 50.7 mmol) was added to a solution of 6 (1.98 g, 4.6
mmol) in anhyd pyridine (60 mL). The reaction mixture was stirred
at r.t. for 24 h, then diluted with toluene (200 mL) and extracted
with 1 M HCl until the aqueous layer remained acidic. The organic
layer was extracted with sat. aq NaHCO3 (2 × 30 mL), H2O (2 × 30
mL), dried over MgSO4 and the solvent was evaporated. Column
chromatography on silica gel (toluene–EtOAc, 20:1) gave the prod-
uct 7.
Yield: 2.96 g (78%); colorless viscous oil.
Method B: LiN3 (299 mg, 6.1 mmol) and 4c (774 mg, 1.14 mmol)
were dissolved in anhyd DMF (26 mL) under an argon atmosphere
and the solution was heated to 120 °C (r.t. to 120 °C in 30 min) at
which time, TLC showed the reaction was complete. The mixture
was cooled to r.t., diluted with brine (400 mL) and extracted with
CHCl3 (4 × 15 mL). The combined organic layers were extracted
with brine (50 mL), dried over MgSO4 and evaporated. Column
chromatography of the residue on silica gel (toluene) afforded 5.
Yield: 1.80 g (82%); colorless liquid; [a]D +53 (c 0.5, CHCl3).
1H NMR (CDCl3, 400 MHz):
d = 7.25–7.37 (m, 10 H,
2 × OCH2C6H5), 5.89 (dddd, J = 16.6, 10.4, 6.3, 5.2 Hz, 1 H,
OCH2CH=CH2), 5.27 (dq, J = 17.2, 1.7 Hz, 1 H, OCH2CH=CH2),
5.26 (t, J = 9.8 Hz, 1 H, H-4), 5.22 (dq, J = 10.4, 1.5 Hz, 1 H,
OCH2CH=CH2), 4.85 (d, J = 1.8 Hz, 1 H, H-1), 4.69 (d, J = 12.1
Hz, 1 H, OCH2C6H5), 4.57 (d, J = 12.1 Hz, 1 H, OCH2C6H5), 4.52
(s, 2 H, OCH2C6H5), 4.18 (ddt, J = 13.0, 5.2, 1.5 Hz, 1 H,
OCH2CH=CH2), 4.00 (dd, J = 9.6, 3.7 Hz, 1 H, H-3), 3.98 (ddt,
J = 13.0, 6.3, 1.4 Hz, 1 H, OCH2CH=CH2), 3.93 (dd, J = 3.7, 1.8
Hz, 1 H, H-2), 3.82 (ddd, J = 9.5, 5.3, 3.8 Hz, 1 H, H-5), 3.55 (dd,
J = 10.7, 5.5 Hz, 1 H, H-6b), 3.51 (dd, J = 10.8, 3.7 Hz, 1 H, H-6a),
1.90 (s, 3 H, OAc).
Yield: 415 mg (86%); colorless viscous oil; [a]D +40 (c 0.4, CHCl3).
1H NMR (CDCl3, 400 MHz): d = 7.25–7.51 (m, 10 H, CHC6H5,
OCH2C6H5), 5.87 (dddd, J = 16.9, 10.5, 6.4, 5.4 Hz, 1 H,
OCH2CH=CH2), 5.62 (s, 1 H, CHC6H5), 5.27 (dq, J = 17.3, 1.7 Hz,
1 H, OCH2CH=CH2), 5.22 (dq, J = 10.3, 1.2 Hz, 1 H, OCH2C6H5),
4.90 (d, J = 12.0 Hz, 1 H, OCH2C6H5), 4.80 (d, J = 1.5 Hz, 1 H, H-
1), 4.74 (d, J = 12.2 Hz, 1 H, OCH2C6H5), 4.09–4.27 (m, 4 H, H-3,
H-5, H-6b, OCH2CH=CH2), 4.01 (dd, J = 3.2, 1.5 Hz, 1 H, H-2),
3.96 (ddt, J = 12.9, 6.1, 1.2 Hz, 1 H, OCH2CH=CH2), 3.80–3.86 (m,
2 H, H-4, H-6a).
13C NMR (CDCl3, 100 MHz): d = 138.01, 137.34, 133.04, 128.90,
128.36 (2 × C), 128.18 (2 × C), 127.67, 127.43 (2 × C), 125.97 (2 ×
C), 118.13, 101.52, 98.19, 79.08, 75.67, 73.28, 68.61, 68.21, 63.84,
62.74.
13C NMR (CDCl3, 100 MHz): d = 169.66, 137.93, 137.60, 133.20,
128.42 (2 × C), 128.26 (2 × C), 127.87, 127.71 (2 × C), 127.64 (2 ×
C), 127.54, 117.94, 97.04, 73.48, 72.27, 70.21, 69.46, 68.43, 68.19,
61.06, 20.80.
MS (ESI): m/z [M + Na]+ calcd for C25H29N3NaO6: 490.20; found:
490.3.
MS (ESI): m/z [M + Na]+ calcd for C23H25N3NaO5: 446.17; found:
446.2.
Anal. Calcd for C25H29N3O6: C, 64.23; H, 6.25; N, 8.99. Found: C,
64.56; H, 6.42; N, 8.74.
Anal. Calcd for C23H25N3O5: C, 65.24; H, 5.95; N, 9.92. Found: C,
65.31; H, 6.03; N, 9.59.
4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-a,b-D-mannopyra-
nose (8)
Allyl 2-Azido-3,6-di-O-benzyl-2-deoxy-a-D-mannopyranoside
(6)
A mixture of 7 (4.09 g, 8.7 mmol) and PdCl2 (100 mg, 0.56 mmol)
in EtOH (11 mL) and MeOH (20 mL) was stirred at r.t. overnight.
PdCl2 (20 mg, 0.11 mmol) was added and the mixture was stirred at
r.t. for 24 h, filtered through Celite and evaporated. Column chro-
matography of the residue on silica gel (toluene–EtOAc, 10:1) af-
forded the product 8.
Triethylsilane (4.4 mL, 27.9 mmol) and TFA (2.2 mL, 29.6 mmol)
were added at 0 °C to a solution of 5 (2.37 g, 5.6 mmol) in anhyd
CH2Cl2 (100 mL). The mixture was stirred at 0 °C for 2 h and then
at r.t. overnight, poured into ice-cold sat. aq NaHCO3 (100 mL) and
extracted with CHCl3 (100 mL). The organic layer was dried over
MgSO4 and the solvent evaporated. Column chromatography on sil-
ica gel (toluene–EtOAc, 20:1) gave the product 6.
Yield: 3.26 g (87%); yellowish syrup; [a]D +33 (c 0.5, CHCl3).
Yield: 1.62 g (68%); colorless viscous oil; [a]D +18 (c 0.5, CHCl3).
1H NMR (400 MHz, CDCl3): d [major anomer (a)] = 7.37–7.26 (m,
10 H, ArH, Bn), 5.16–5.10 (m, 1 H, H-1), 5.12 (t, J = 9.7 Hz, 1 H,
H-4), 4.67 (d, J = 12.1 Hz, 1 H, CH2-Ph), 4.55 (d, J = 12.1 Hz, 1 H,
CH2-Ph), 4.50 (s, 2 H, CH2-Ph), 4.03 (ddd, J = 2.6, 7.5, 10.1 Hz,
1 H, H-5), 3.99 (dd, J = 3.7, 9.3 Hz, 1 H, H-3), 3.82 (dd, J = 1.8, 3.5
Hz, 1 H, H-2), 3.69 (d, J = 3.5 Hz, 1 H, OH), 3.54 (dd, J = 7.6, 10.5
Hz, 1 H, H-6a), 3.43 (dd, J = 2.8, 10.5 Hz, 1 H, H-6b), 1.92 (s, 3 H,
OCOCH3).
13C NMR (100 MHz, CDCl3): d = 169.81 (CH3CO), 137.57, 137.45,
128.46 (2 × C), 128.36 (2 × C), 128.10 (2 × C), 127.93, 127.82,
127.69 (2 ×C, CAr, Bn), 92.61, 76.06, 73.52 (CH2-Ph), 72.27, 69.90
(CH2-Ph), 69.68, 68.41, 61.27, 20.81 (CH3CO).
1H NMR (CDCl3, 400 MHz):
d = 7.25–7.41 (m, 10 H,
2 × OCH2C6H5), 5.87 (dddd, J = 17.1, 10.5, 6.3, 5.2 Hz, 1 H,
OCH2CH=CH2), 5.26 (dq, J = 17.1, 1.5 Hz, 1 H, OCH2CH=CH2),
5.20 (dq, J = 10.4, 1.2 Hz, 1 H, OCH2CH=CH2), 4.84 (d, J = 1.7 Hz,
1 H, H-1), 4.75 (d, J = 11.6 Hz, 1 H, OCH2C6H5), 4.65 (d, J = 11.1
Hz, 1 H, OCH2C6H5), 4.62 (d, J = 11.8 Hz, 1 H, OCH2C6H5), 4.56
(d, J = 12.2 Hz, 1 H, OCH2C6H5), 4.16 (ddt, J = 12.8, 5.0, 1.5 Hz,
1 H, OCH2CH=CH2), 3.89–3.99 (m, 4 H), 3.71–3.77 (m, 3 H, H-2,
H-3, H-4, H-5, H-6a, H-6b, OCH2CH=CH2), 2.58 (br s, 1 H, OH).
13C NMR (CDCl3, 100 MHz): d = 137.97, 137.52, 133.27, 128.57
(2 × C), 128.33 (2 × C), 128.05, 127.92 (2 × C), 127.60, 127.56
(2 × C), 117.80, 97.32, 79.25, 73.53, 72.44, 71.14, 69.95, 68.04,
67.90, 60.41.
MS (ESI): m/z = 450.2 [M + Na]+.
Anal. Calcd for C22H25N3O6: C, 61.82; H, 5.90; N, 9.83. Found: C,
61.84; H, 5.85; N, 9.54.
Synthesis 2008, No. 16, 2610–2616 © Thieme Stuttgart · New York

PAPER
a(1→4)-Linked Oligosaccharides of the D-Mannosamine Type
2615
O-(4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-mannopy-
ranosyl) Trichloroacetimidate (9)
5.25 (dq, J = 1.4, 10.4 Hz, 1 H, OCH2CH=CH2), 5.19 (t, J = 9.4 Hz,
1 H, H-4¢), 5.17 (d, J = 2.2 Hz, 1 H, H-1¢), 4.87 (d, J = 1.8 Hz, 1 H,
H-1), 4.73 (d, J = 11.3 Hz, 1 H, OCH2C6H5), 4.51 (d, J = 12.0 Hz,
1 H, OCH2C6H5), 4.50 (d, J = 11.9 Hz, 1 H, OCH2C6H5), 4.45 (d,
J = 12.1 Hz, 1 H, OCH2C6H5), 4.44 (d, J = 12.1 Hz, 1 H,
OCH2C6H5), 4.44 (d, J = 11.3 Hz, 1 H, OCH2C6H5), 4.43 (d,
J = 12.0 Hz, 1 H, OCH2C6H5), 4.41 (d, J = 11.9 Hz, 1 H,
OCH2C6H5), 4.20 (ddt, J = 1.5, 5.2, 12.9 Hz, 1 H, OCH2CH=CH2),
4.01 (dd, J = 1.8, 3.5 Hz, 1 H, H-2), 4.01 (ddt, J = 1.3, 6.2, 12.9 Hz,
1 H, OCH2CH=CH2), 3.99 (dd, J = 3.5, 9.5 Hz, 1 H, H-3), 3.95 (t,
J = 9.5 Hz, 1 H, H-4), 3.73–3.84 (m, 3 H, H-5, H-6a, H-6b), 3.80
(dd, J = 3.5, 9.2 Hz, 1 H, H-3¢), 3.72 (ddd, J = 3.5, 5.4, 9.6 Hz, 1 H,
H-5¢), 3.63 (dd, J = 2.2, 3.5 Hz, 1 H, H-2¢), 3.34 (dd, J = 5.4, 10.6
Hz, 1 H, H-6b¢), 3.37 (dd, J = 3.5, 10.6 Hz, 1 H, H-6a¢), 1.89 (s, 3 H,
OAc).
13C NMR (CDCl3, 125 MHz): d = 169.6 (CH3CO), 138.4, 137.9,
137.7, 136.8 (CAr, Bn), 133.3 (OCH2CH=CH2), 128.8 (2 × C), 128.4
(4 × C), 128.3 (2 × C), 128.2 (2 × C), 128.0, 127.8 (4 × C), 127.5
(2 × C), 127.4 (2 × C), 127.4 (CAr, Bn), 118.0 (OCH2CH=CH2),
100.1 (C-1¢), 97.0 (C-1), 79.7 (C-3), 76.6 (C-3), 74.4 (C-4), 73.5,
73.2, 72.1, 71.6 (CH2Ph), 71.3 (C-5¢), 71.0 (C-5), 69.7 (C-6¢), 69.5
(C-6), 68.4 (C-4¢), 68.3 (OCH2CH=CH2), 61.0 (C-2¢), 60.0 (C-2),
20.8 (CH3CO).
Method A: Trichloroacetonitrile (0.8 mL, 7.97 mmol) was added to
a solution of 8 (276 mg, 0.64 mmol) in anhyd toluene (20 mL) at
0 °C. A solution of DBU (0.12 mL, 0.80 mmol) in anhyd toluene
(0.5 mL) was added dropwise and the mixture was stirred at 0 °C for
45 min and then at r.t. overnight. The mixture was extracted with aq.
NH4Cl (2.5 M, 20 mL) and the organic layer was washed with H2O
(20 mL), dried over MgSO4 and evaporated. Column chromatogra-
phy of the residue on silica gel (toluene–EtOAc, 25:1) afforded 9
(146 mg, 39%) as a yellowish viscous oil.
Method B: Compound 8 (926 mg, 2.1 mmol) was dissolved in anhyd
CH2Cl2 (20 mL) and trichloroacetonitrile (2.3 mL, 22.9 mmol) was
added. The mixture was cooled to 0 °C and DBU (80 mL, 0.56
mmol) was added dropwise. The mixture was stirred at 0 °C for 1.5
h and then for 2.5 h at r.t., then evaporated to dryness. Column chro-
matography of the residue on silica gel (toluene–EtOAc, 25:1) af-
forded 9 (868 mg, 70%) as a yellowish viscous oil.
[a]D +49 (c 0.7, CHCl3).
1H NMR (CDCl3, 400 MHz): d = 8.66 (s, 1 H, NH), 7.25–7.37 (m,
10 H, 2 × OCH2C6H5), 6.20 (d, J = 1.8 Hz, 1 H, H-1), 5.40 (t,
J = 9.6 Hz, 1 H, H-4), 4.66 (s, 2 H, OCH2C6H5), 4.53 (d, J = 12.1
Hz, 1 H, OCH2C6H5), 4.49 (d, J = 12.1 Hz, 1 H, OCH2C6H5), 3.96–
4.04 (m, 3 H, H-2, H-3, H-5), 3.54 (m, 2 H, H-6a, H-6b), 1.94 (s,
3 H, OAc).
MS (ESI): m/z [M + Na]+ calcd for C45H50N6NaO10: 857.35; found:
857.5.
Anal. Calcd for C45H50N6O10: C, 64.74; H, 6.04; N, 10.07. Found:
C, 65.01; H, 6.32; N, 9.74.
13C NMR (CDCl3, 100 MHz): d = 169.52, 159.77, 137.75, 137.11,
128.58 (2 × C), 128.27 (2 × C), 128.22, 128.17 (2 × C), 127.86 (2 ×
C), 127.61, 95.73, 90.63, 75.78, 73.49, 72.95, 72.73, 69.01, 67.71,
59.64, 20.82.
MS (ESI): m/z [M + Na]+ calcd for C25H29N3NaO6: 593.07; found:
593.0.
Allyl 2-Azido-3,6-di-O-benzyl-2-deoxy-a-D-mannopyranosyl-
(1→4)-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-mannopyranoside
(11)
A solution of MeONa in MeOH (0.092 M, 15 mL) was added drop-
wise to a solution of 10 (910 mg, 1.09 mmol) in anhyd MeOH (50
mL). The mixture was stirred for 24 h at r.t., then neutralized with
Dowex-50 (pyridinium form), the solid was filtered off and the sol-
vent was evaporated. Column chromatography of the residue on sil-
ica gel (toluene–EtOAc, 10:1) afforded 11.
Anal. Calcd for C24H25Cl3N4O6: C, 50.41; H, 4.41; Cl, 18.60; N,
9.80. Found: C, 50.52; H, 4.57; Cl, 18.43; N, 9.57.
Allyl 4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-manno-
pyranosyl-(1→4)-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-manno-
pyranoside (10)
Yield: 708 mg (82%); yellowish oil; [a]D +32 (c 0.4, CHCl3).
Method A: A mixture of compounds 9 (259 mg, 0.45 mmol) and 6
(163 mg, 0.38 mmol) in anhyd CH2Cl2 (8 mL) was stirred with pow-
dered 4 Å MS (240 mg) for 30 min under an argon atmosphere. Af-
ter cooling to –50 °C, TMSOTf (105 mL, 0.57 mmol) was added and
the mixture was stirred at –50 °C for 2 h and then allowed to warm
up to r.t. and stirred overnight. The mixture was diluted with CHCl3
(10 mL) and neutralized with sat. aq NaHCO3. The organic layer
was extracted with H2O (10 mL), dried over MgSO4 and evaporat-
ed. Column chromatography of the residue on silica gel (toluene–
EtOAc, 20:1) afforded 10 (192 mg, 60% relative to acceptor) as a
yellowish oil.
IR (CHCl3): 3600 (w), 3507 [w, br (n OH)], 2109 [vs (nas N3)], 1056
[s (partly n C–OH)].
1H NMR (500 MHz, CDCl3):
d = 7.40–7.20 (m, 20 H,
4 × OCH2C6H5), 5.91 (dddd, J = 5.2, 6.2, 10.4, 17.2 Hz, 1 H,
OCH2CH=CH2), 5.30 (dq, J = 1.7, 17.2 Hz, 1 H, OCH2CH=CH2),
5.24 (ddt, J = 1.2, 1.6, 10.4 Hz, 1 H, OCH2CH=CH2), 5.15 (d,
J = 1.8 Hz, 1 H, H-1¢), 4.87 (d, J = 1.7 Hz, 1 H, H-1), 4.74 (d,
J = 11.3 Hz, 1 H, CH2-Ph), 4.56 (d, J = 11.5 Hz, 1 H, CH2-Ph), 4.53
(d, J = 11.9 Hz, 1 H, CH2-Ph), 4.51 (d, J = 11.5 Hz, 1 H, CH2-Ph),
4.49 (d, J = 11.9 Hz, 1 H, CH2-Ph), 4.47 (d, J = 12.2 Hz, 1 H, CH2-
Ph), 4.46 (d, J = 12.2 Hz, 1 H, CH2-Ph), 4.43 (d, J = 11.3 Hz, 1 H,
CH2-Ph), 4.19 (ddt, J = 1.5, 5.2, 12.9 Hz, 1 H, OCH2CH=CH2),
4.02–3.97 (m, 4 H, OCH2CH=CH2, H-2, H-3, H-4), 3.91 (t, J = 9.5
Hz, 1 H, H-4¢), 3.74–3.65 (m, 5 H, H-5, H-6a, H-6b H-3¢, H5¢), 3.66
(dd, J = 1.8, 3.5 Hz, 1 H, H-2¢), 3.58 (dd, J = 4.8, 10.2 Hz, 1 H, H-
6¢a), 3.54 (dd, J = 4.2, 10.2 Hz, 1 H, H-6¢b).
Method B: A mixture of 9 (76 mg, 0.17 mmol), Ph2SO (80 mg, 0.39
mmol) and TTBP (145 mg, 0.58 mmol) in anhyd CH2Cl2 (4 mL)
with powdered 4 Å MS (210 mg) was stirred for 30 min at r.t. under
an argon atmosphere, then cooled to –48 °C and Tf2O (32 mL, 0.19
mmol) was added dropwise. The mixture was allowed to warm to
–25 °C (in 25 min) and stirred at this temperature for 30 min. A so-
lution of 6 (61 mg, 0.14 mmol) in anhyd CH2Cl2 (1 mL) was added
dropwise and the mixture was warmed to r.t. (in 2 h) and stirred at
r.t. overnight. The reaction was quenched with Et3N (1 mL) and
evaporated to dryness. Column chromatography of the residue on
silica gel (toluene → toluene–EtOAc, 5:1) afforded 10 (94 mg, 78%
relative to acceptor) as a yellowish oil.
13C NMR (125 MHz, CDCl3): d = 138.31, 137.91, 137.65, 136.88
(CAr), 133.33 (OCH2CH=CH2), 128.76, 128.52, 128.35, 128.33,
128.23, 128.02, 127.96, 127.81 (2 × C), 127.65 (2 × C), 127.62,
127.42 (2 × C), 127.38 (CAr), 117.92 (OCH2CH=CH2), 100.28 (C-
1¢), 96.99 (C-1), 79.71 (C-3), 78.97 (C-3¢), 74.00 (C-4), 73.61,
73.29, 72.31 (CH2-Ph), 71.94 (C-5¢), 71.63 (CH2-Ph), 71.24 (C-5),
70.18 (C-6¢), 69.42 (C-6), 68.24 (OCH2CH=CH2), 68.11 (C-4¢),
60.37 (C-2¢), 60.07 (C-2).
[a]D +25 (c 0.4, CHCl3).
1H NMR (CDCl3, 500 MHz):
4 × OCH2C6H5), 5.93 (dddd, J = 5.2, 6.2, 10.4, 17.4 Hz, 1 H,
OCH2CH=CH2), 5.31 (dq, J = 1.6, 17.4 Hz, 1 H, OCH2CH=CH2),
d = 7.19–7.42 (m, 20 H,
MS (ESI): m/z [M + Na]+ calcd for C43H48N6NaO9: 815.34; found:
815.3.
Synthesis 2008, No. 16, 2610–2616 © Thieme Stuttgart · New York

2616
M. Turský et al.
PAPER
MS (HR-FAB): m/z [M + H]+ calcd for C43H49N6O9: 793.3561;
MS (ESI): m/z [M + Na]+ calcd for C65H71N9NaO14: 1224.5018;
found: 793.3540.
found: 1224.5070.
Allyl 4-O-Acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-manno-
pyranosyl-(1→4)-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-manno-
pyranosyl-(1→4)-2-azido-3,6-di-O-benzyl-2-deoxy-a-D-manno-
pyranoside (12)
Acknowledgment
We are thankful for the support to the Grant Agency of Czech Aca-
demy of Science (grant No. KAN200520703), Ministry of Educa-
tion of the Czech Republic (project No. LC06070 and MSM
0021620857), Grant Agency of Ministry of Agriculture of the
Czech Republic (grant No. QF3115/2003) and research project No.
Z4 055 0506.
Method A: A mixture of 9 (122 mg, 0.21 mmol), 11 (134 mg, 0.168
mmol) and powdered 4 Å MS (240 mg) in anhyd CH2Cl2 (10 mL)
was stirred at r.t. for 30 min under an argon atmosphere. The mix-
ture was cooled to –50 °C and TMSOTf (50 mL, 0.07 mmol) was
added dropwise. The mixture was stirred at –50 °C for 2 h and then
slowly warmed to r.t. (within 2 h) and stirred at this temperature
overnight. CHCl3 (15 mL) was added and the solution was washed
with sat. aq NaHCO3 (2 × 30 mL) and H2O (10 mL). The organic
phase was dried over MgSO4 and the solvent was evaporated. Col-
umn chromatography of the residue on silica gel (toluene–EtOAc,
30:1) afforded 12 as a yellowish oil [83 mg (41% to acceptor)];
When the reaction was performed on a 0.056 mmol scale (of the ac-
ceptor), the yield was 60%.
References
(1) Present address: Center for Sustainable and Green
Chemistry, Department of Chemistry, Building 201,
Technical University of Denmark, 2800 Kgs. Lyngby,
Denmark.
(2) Dwek, R. A. Chem. Rev. 1996, 96, 683.
(3) Varki, A. Glycobiology 1993, 3, 97.
Method B: A mixture of 8 (72 mg, 0.168 mmol), Ph2SO (74 mg,
0.36 mmol), TTBP (135 mg, 0.54 mmol) and powdered 4 Å MS
(240 mg) was stirred in anhyd CH2Cl2 (4 mL) under an argon atmo-
sphere at r.t. for 20 min. After cooling to –52 °C, Tf2O (30 mL, 0.178
mmol) was added dropwise and the mixture was warmed to –25 °C
in 30 min and stirred at this temperature for 30 min. A solution of
11 (92 mg, 0.116 mmol) in anhyd CH2Cl2 (2 mL) was added drop-
wise and the mixture was warmed to r.t. in 2 h and stirred at r.t.
overnight. The reaction was quenched with Et3N (1 mL) and evap-
orated to dryness. Column chromatography of the residue on silica
gel (toluene → toluene–EtOAc, 5:1) afforded 12 (91 mg, 65% to ac-
ceptor) as a yellowish oil
(4) Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res. 2007,
342, 374.
(5) Banoub, J.; Boullanger, P.; Lafont, D. Chem. Rev. 1992, 92,
1167.
(6) Gridley, J. J.; Osborn, H. M. I. J. Chem. Soc., Perkin Trans.
1 2000, 10, 1471.
(7) Veselý, J.; Ledvina, M.; Jindřich, J.; Trnka, T.; Šaman, D.
Collect. Czech. Chem. Commun. 2004, 69, 1914.
(8) Beynon, L. M.; Richards, J. C.; Perry, M. B.; Kniskern, P. J.
Can. J. Chem. 1992, 70, 218.
(9) Osa, Y.; Kaji, E.; Takahashi, K.; Hirooka, M.; Zen, S.;
Lichtenthaler, F. W. Chem. Lett. 1993, 1567.
(10) Silipo, A.; Molinaro, A.; Lanzetta, R.; Parrilli, M.; Lindner,
B.; Holst, O. Eur. J. Org. Chem. 2004, 1336.
(11) Litjens, R. E. J. N.; Leeuwenburgh, M. A.; van der Marel, G.
A.; van Boom, J. H. Tetrahedron Lett. 2001, 42, 8693.
(12) Litjens, R. E. J. N.; van den Bos, L. J.; Codée, J. D. C.;
van den Berg, R. J. B. H. N.; Overkleeft, H. S.;
van der Marel, G. A. Eur. J. Org. Chem. 2005, 918.
(13) van den Bos, L. J.; Duivenvoorden, B. A.; de Koning, M. C.;
Filippov, D. V.; Overkleeft, H. S.; van der Marel, G. A. Eur.
J. Org. Chem. 2007, 116.
(14) Crich, D.; Chandrasekera, N. S. Angew. Chem. Int. Ed. 2004,
43, 5386.
(15) Veselý, J.; Rohlenová, A.; Dýžoganová, M.; Trnka, T.;
Tišlerová, I.; Šaman, D.; Ledvina, M. Synthesis 2006, 699.
(16) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21.
[a]D +28 (c 0.2, CHCl3).
IR (CHCl3): 2110 [vs (nas N3)], 1745 [w (n C=O)].
1H NMR (500 MHz, CDCl3):
d = 7.42–7.17 (m, 30 H,
6 × OCH2C6H5), 5.95 (dddd, J = 5.2, 6.2, 10.2, 17.2 Hz, 1 H,
OCH2CH=CH2), 5.33 (dq, J = 1.6, 17.2 Hz, 1 H, OCH2CH=CH2),
5.29 (ddt, J = 1.2, 1.7, 10.2 Hz, 1 H, OCH2CH=CH2), 5.20 (dd,
J = 9.8, 10.8 Hz, 1 H, H-4¢¢), 5.14 (d, J = 2.1 Hz, 1 H, H-1¢), 5.12 (d,
J = 2.2 Hz, 1 H, H-1¢¢), 4.90 (d, J = 1.8 Hz, 1 H, H-1), 4.80 (d,
J = 11.3 Hz, 1 H, CH2-Ph), 4.53 (d, J = 12.0 Hz, 1 H, CH2-Ph), 4.52
(d, J = 11.9 Hz, 1 H, CH2-Ph), 4.47 (d, J = 11.3 Hz, 1 H, CH2-Ph),
4.45 (d, J = 12.0 Hz, 1 H, CH2-Ph), 4.45 (d, J = 11.3 Hz, 1 H, CH2-
Ph), 4.42 (d, J = 11.9 Hz, 2 H, 2 × CH2-Ph), 4.41 (d, J = 12.0 Hz,
1 H, CH2-Ph), 4.38 (d, J = 11.9 Hz, 1 H, CH2-Ph), 4.37 (d, J = 12.0
Hz, 1 H, CH2-Ph), 4.23 (d, J = 11.3 Hz, 1 H, CH2-Ph), 4.23 (ddt,
J = 1.5, 5.2, 12.9 Hz, 1 H, OCH2CH=CH2), 4.08 (dd, J = 1.8, 3.5
Hz, 1 H, H-2), 4.04 (dd, J = 3.5, 9.0 Hz, 1 H, H-3), 4.03 (ddt,
J = 1.2, 6.2, 12.9 Hz, 1 H, OCH2CH=CH2), 3.94 (dd, J = 9.0, 9.5
Hz, 1 H, H-4), 3.90 (dd, J = 9.2, 9.6 Hz, 1 H, H-4¢), 3.81–3.78 (m,
4 H, H-6b, H-5, H-3¢, H-3¢¢), 3.74 (ddd, J = 3.6, 5.1, 9.8 Hz, 1 H, H-
5¢¢), 3.70 (ddd, J = 1.9, 5.5, 9.2 Hz, 1 H, H-5¢), 3.69 (dd, J = 2.1, 3.3
Hz, 1 H, H-2¢), 3.66 (dd, J = 5.0, 11.5 Hz, 1 H, H-6a), 3.64 (dd,
J = 2.2, 3.5 Hz, 1 H, H-2¢¢), 3.60 (dd, J = 1.9, 11.0 Hz, 1 H, H-6¢b),
3.52 (dd, J = 5.5, 11.0 Hz, 1 H, H-6¢a), 3.37 (dd, J = 5.1, 10.6 Hz,
1 H, H-6¢¢b), 3.35 (dd, J = 3.6, 10.6 Hz, 1 H, H-6¢¢a), 1.88 (s, 3 H,
CH3CO).
(17) Gin, D. J. Carbohydr. Chem. 2002, 21, 645.
(18) Tanaka, H.; Kawai, K.; Fujiwara, K.; Murai, A. Tetrahedron
2002, 58, 10017.
(19) Jenkins, D. J.; Potter, B. V. L. Carbohydr. Res. 1994, 265,
145.
(20) Codée, J. D. C.; van den Bos, L. J.; Litjens, R. E. J. N.;
Overkleeft, H. S.; van Boeckel, C. A. A.; van Boom, J. H.;
van der Marel, G. A. Tetrahedron 2004, 60, 1057.
(21) Gattuso, G.; Nepogodiev, S. A.; Stoddart, J. F. Chem. Rev.
1998, 98, 1919.
13C NMR (125 MHz, CDCl3): d = 169.55 (CH3CO), 138.30, 137.86,
137.70, 136.84, 136.82 (CAr), 133.33 (OCH2CH=CH2), 118.00
(OCH2CH=CH2), 100.16 (C-1¢), 96.89 (C-1¢¢), 96.95 (C-1), 79.64
(C-3), 79.32 (C-3¢), 76.70 (C-3¢¢), 74.79 (C-4), 74.02 (C-4¢), 73.53,
73.41, 73.28 (CH2-Ph), 72.12 (C-5¢), 72.03, 71.52, 71.46 (CH2-Ph),
71.43 (C-5), 70.91 (C-5¢¢), 69.85 (C-6), 69.69 (C-6¢), 69.37 (C-6¢¢),
68.42 (C-4¢¢), 68.36 (OCH2CH=CH2), 60.90 (C-2¢¢), 59.85 (C-2),
59.81 (C-2¢), 20.82 (CH3CO).
(22) Hofman-Bang, N. Acta Chem. Scand. 1957, 11, 581.
(23) Jenkins, D. J.; Potter, B. V. L. Carbohydr. Res. 1996, 287,
169.
(24) Holme, K. R.; Hall, L. D. Carbohydr. Res. 1992, 225, 291.
(25) Fukase, K.; Matsumoto, T.; Ito, N.; Yoshimura, T.; Kotani,
S.; Kusumoto, S. Bull. Chem. Soc. Jpn. 1992, 65, 2643.
(26) Peer, A.; Vasella, A. Helv. Chim. Acta 1999, 82, 1044.
Synthesis 2008, No. 16, 2610–2616 © Thieme Stuttgart · New York