4-O-Acetyl-3-O-tert-butyldimethylsilyl-l-rhamnal: a building block in the stereoselective synthesis of 2-deoxy-α-l-rhamnopyranosides

Article abstract of DOI:10.1016/j.carres.2006.09.007

The stereoselective synthesis of 2-deoxy-α-l-glycosides by addition of various acceptors to 4-O-acetyl-3-O-tert-butyldimethylsilyl-l-rhamnal promoted by triphenylphosphine-hydrogen bromide is developed.

Full text of DOI:10.1016/j.carres.2006.09.007

Carbohydrate Research 341 (2006) 2702–2707
Note
4-O-Acetyl-3-O-tert-butyldimethylsilyl-L-rhamnal: a building block
in the stereoselective synthesis of 2-deoxy-a-L-rhamnopyranosides
*
Ilona Wandzik and Tadeusz Bieg
Silesian University of Technology, Faculty of Chemistry, Department of Organic Chemistry,
Bioorganic Chemistry and Biotechnology, 44-100 Gliwice, Krzywoustego 4, Poland
Received 15 July 2006; received in revised form 29 August 2006; accepted 6 September 2006
Available online 2 October 2006
Abstract—The stereoselective synthesis of 2-deoxy-a-L-glycosides by addition of various acceptors to 4-O-acetyl-3-O-tert-butyldi-
methylsilyl-L-rhamnal promoted by triphenylphosphine–hydrogen bromide is developed.
Ó 2006 Elsevier Ltd. All rights reserved.
Keywords: Glycals; 2-Deoxyglycosides; Stereoselective synthesis
Glycals are versatile synthetic intermediates for the
preparation of 2-deoxy glycosides and 2,3-unsaturated
glycosides that can be easily functionalised at the C-2
for instance, triphenylphosphine–hydrogen bromide
1
2
13
(TPHB), cation-exchange resin Dowex AG 50WX2,
1
4
15
BCl , BBr , CAN or the CeCl –NaI reagent sys-
3
16
3
3
1
–4
and C-3 positions.
2,6-Dideoxyglycosidic linkages
tem. According to these procedures, 2-deoxy-a-glyco-
sides are formed as the major products.
are present in many bioactive natural products such as
anthracycline antibiotics, aureolic acids and cardiac gly-
cosides. Therefore, utilisation of glycals as building
blocks for the total synthesis of various natural products
is of great interest in bioorganic and medicinal chemis-
The work described in this report is based on the
1
2
Falck–Mioskowski route where TPHB is the catalyst
for a mild and high-yield protonation, followed by gly-
cosylation of glycals. This procedure has a lot of appli-
cations in the synthesis of several precursors of bioactive
compounds when specificity and mild conditions are
4
–8
try.
Glycals compare well with fully oxygenated pyranose
derivatives due to their relative ease in differentiation of
hydroxyl groups by selective protection. Moreover,
glycals can be exploited, not only as glycosyl donors,
1
7–21
required.
Stereoselectivity in these procedures
depends mostly on the nature of the starting materials.
2,6-Dideoxy-L-arabino- and L-lyxo-hexopyranoses are
common structural units in natural products. Both of
them can be obtained from L-rhamnal, the former by
direct addition of an alcohol, and the latter by addition,
2
,9,10
but also as glycosyl acceptors.
This approach
enables an efficient, reiterative synthesis of complex
oligosaccharides.
2
2,23
One possible way for the exploration of glycals as gly-
cosyl donors is to investigate the direct addition of alco-
hols to the double bond of glycals. This reaction should
take place under mild conditions in order to provide
preference over the Ferrier rearrangement, which is a
followed by inversion of configuration at C-4.
We describe herein our studies on the stereoselectivity
in the addition of various acceptors to derivatives of L-
rhamnal promoted by TPHB. Stereoselectivity in glyco-
sylation reactions is a key feature, especially since in the
synthesis of complex oligosaccharides, the separation of
isomeric glycosides is difficult and often even impossible.
Therefore, within a synthetic project directed to the
preparation of analogues of 2,6-dideoxy-L-arabino-
hexopyranose we have undertaken studies aiming at
1
1
competing reaction. Successful direct addition can
be accomplished in the presence of several catalysts,
*
Corresponding author. Tel.: +48 32 2372028; e-mail: ilona.
wandzik@polsl.pl
0
008-6215/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.09.007

I. Wandzik, T. Bieg / Carbohydrate Research 341 (2006) 2702–2707
2703
improving stereoselectivity. It was interesting to exam-
Table 1. Addition of acceptors 5–12 to L-rhamnal derivatives 1–4
Entry Glycal Acceptor Product a:b Reaction Yield
time (%)
5:1 6 h
ine if the stereoselective outcome of the Falck–Mios-
kowski method is influenced by the protecting group
at C-3. Recently we have found that reaction of glycal
1
1
10
13
65
3
with 1-O-benzyl-2-O-octanoyl-sn-glycerol (8) was
2
1
2
3
4
5
6
7
8
5
14
15
16
17
18
19
20
3:1 10 min
4:1 10 min
4:1 1 h
5:1 30 min
4.5:1 30 min
6:1 10 min
6:1 2.5 h
81
71
51
85
59
76
55
highly selective for the a-glycoglycerolipid 23. Now,
in order to evaluate the range of applicability of this
process, various acceptors 5–12 were reacted with
L-rhamnal derivatives 1–4 (Scheme 1).
We initially examined the glycosylation of glycals 1
and 2 with a small excess (1.2 equiv) of selected accep-
tors in the presence of a catalytic amount of TPHB
6
7
21
2
8
9
10
11
9
10
11
12
6
21
22
23
24
25
26
27
4:1 20 min
4:1 1.5 h
15:1 45 min
15:1 1 h
1:0 1 h
76
58
55
63
78
45
79
(
0.1 equiv) in CH Cl at room temperature. Reactions
2 2
7
2
1
afforded the corresponding 2-deoxy glycosides 13–20
as chromatographically inseparable mixtures of a and
b anomers regardless of the acceptor applied. As shown
in Table 1 (entries 1–8) the a:b ratio may have slightly
changed depending on the acceptor used, but in all cases
8
3
4
9
13
14
15
10
11
12
12:1 5 h
1:0 2 h
2
-deoxy-a-L-glycosides were preferentially formed. The
16
10
28
5.5:1 20 min
59
stereoselectivity was not influenced by the solvent. When
toluene was used instead of CH Cl in the glycosylation
2
2
of 3 with 10, we obtained the same mixture of anomers.
Similarly decreasing the reaction temperature to ꢀ25 °C
did not significantly affect the stereoselectivity of the
reaction. Glycosylations of 1 and 2 with 10 (Table 1,
R2O
O
2
R O
O
TPHB
OR
Me
Me
+
ROH
CH Cl , rt
2
2
OR1
OR1
Glycals:
AcO
BnO
AcO
BnO
O
O
O
O
Me
Me
Me
Me
OAc
OBn
OTBDMS
OTBDMS
1
2
3
4
Acceptors:
Me
Me
Me
Me
OH
Me
HO
HO
5
6
7
Me
Me
OH
O
O
OH
O
O
O
O SEt
OCOC H
OCOC11H23
OCOC11H23
7
15
O
OH
OBn
Me
HO
OBn HO
O
2
O
Me BnO
Me
Me
1
O
O
OBn
8
9
Me
Me
1
0
11
12
TBDMS = tert-butyldimethylsilyl
TPHB = triphenylphosphine-hydrogen bromide
Scheme 1.

2704
I. Wandzik, T. Bieg / Carbohydrate Research 341 (2006) 2702–2707
entries 1 and 7) clearly showed that a similar a:b ratio
was obtained irrespective of the protecting group at
C-3, which was either electron-donating or electron-
withdrawing. However, electron factors associated with
the nature of the protecting group affected the reaction
rate. Considering the reaction times required for the
completion of the reaction, benzyl groups in glycal 2
increased the reaction rate in comparison with acetyl
groups in glycal 1.
Once the intermediate was formed, it was attacked by
the nucleophile at either the a or b face. The authors
concluded that the prevailing axial stereoselectivity at
C-1 in the case of glycals with all equatorial substituents
arose from the kinetic anomeric effect. Our results sug-
gest that the addition mechanism is not only kinetically,
but also sterically controlled. The kinetic anomeric effect
can be enhanced by steric factors. Geometries of both
oxonium ion and glycosyl acceptor acting as a nucleo-
phile are essential. It is probable that the substituent
present at the equatorially oriented C-3 position in the
intermediate oxonium ion determines the stereoselectiv-
ity of the nucleophilic attack. The tert-butyldimethyl-
silyloxy group at the C-3 position presents significantly
more steric hindrance to the approach of the nucleophile
than the benzyl or acetyl group does in glycals 1 and 2,
respectively. Thus the approach of the nucleophile from
the bottom b-face of the oxonium ion is sterically
hindered by tert-butyldimethylsilyloxy group. The top
a-face of the intermediate is less hindered, and the major
product is formed by nucleophilic attack from this
direction.
The ratio of stereoisomers was determined by exami-
1
nation of the H NMR spectra of isomer mixtures.
The equatorially oriented H-1a proton of the major a
isomer gave the characteristic broad doublet at d 4.8–
5
.0 ppm with J1,2ax 2.7–3.2 Hz, while the axially oriented
H-1b proton was observed at d 4.4–4.6 ppm as doublet
of doublets with J1,2eq between 2.0 and 2.2 Hz and
J1,2ax 9.8 Hz.
Significant predominance of the a anomer was seen
when glycal 3 with a bulky group at the C-3 position
was applied in reactions with glycerol derivatives 8
and 9 (Table 1, entries 11–12). Glycoglycerolipids 23
and 24 were formed as the predominant 2-deoxy-a-L-
glycosides (a:b = 15:1) showing the superiority of glycal
We have proved that the easily prepared glycal 3 can
be a useful building block in the synthesis of 2-deoxy-a-
L-glycosides. It is reasonable to expect that the stereo-
selective outcome observed for compounds 23–27 would
be similar when glycal 3 is applied in the synthesis of tri-
saccharides and complex 2-deoxy-a-glycosides.
3
over the perbenzylated glycal 2. Unfortunately, we
observed poor stereoselectivity when glycal 3 was
employed in reactions with cyclohexanol and
6
cholesterol 7 with an easily accessible hydroxyl group.
In final experiments, glycal 3 was coupled with mono-
saccharides 10–12 providing exclusively the a-disaccha-
rides. No signals for the b isomers of compounds 25
1
3
and 27 in their C NMR spectra were detected.
All 2-deoxy glycosides were purified by column
chromatography and characterised on the basis of mass
1. Experimental
1.1. Materials and methods
1
13
spectrometry and H and C NMR spectroscopy.
Compounds 13, 16, 19, 20 were identified by comparison
NMR spectra were recorded for solutions in CDCl3
2
4
with literature data. All new compounds gave satisfac-
(internal Me Si) with a Varian spectrometer at a fre-
4
1
13
tory H and C NMR spectra as well as ESIMS analy-
sis (for details see Section 1).
quency of 300 MHz. Optical rotations were measured
with a Perkin–Elmer 141 polarimeter using a sodium
lamp (589 nm) at room temperature. Mass spectra were
recorded in the positive-ion mode on a Mariner (Persep-
tive Biosystem) detector using the electrospray-ionisa-
tion (ESI) technique.
In the course of our investigations we have found that
the presence of a tert-butyldimethylsilyloxy group at the
C-3 position in L-rhamnal derivative 3 beneficially led to
total a-stereoselectivity. An addition to their steric
effect, a second factor that influences stereoselectivity
is the relative reactivity of the L-rhamnal substrate.
When glycal 4 was used in the reaction with acceptor
Reactions were monitored by TLC on precoated
plates of silica gel G (E. Merck), and components were
detected by charring with 10% sulfuric acid in ethanol.
Column chromatography was performed on Silica Gel
60 (70–230 mesh, E. Merck) developed with one of the
hexane–EtOAc solvent systems: A, 8:1; B, 15:1 or C,
25:1 (v/v). All evaporations were performed under
diminished pressure at 50 °C.
1
0, disaccharide 28 was obtained without significant
stereoselectivity, although the sterically demanding tert-
butyldimethylsilyloxy group was present at the C-3 posi-
tion. Considering the reaction times, glycal 4 is more
reactive than glycal 3.
2
6a
Franck and co-workers shed light on the mechanism
of the TPHB-mediated addition of acceptors to gly-
3,4-Di-O-acetyl-L-rhamnal (1),
3,4-di-O-benzyl-L-
2
7
rhamnal (2), 4-O-acetyl-3-O-tert-butyldimethylsilyl-L-
rhamnal (3), 1,2:3,4-di-O-isopropylidene-a-D-galacto-
pyranose (10), 1,2:5,6-di-O-isopropylidene-a-D-gluco-
furanose (11) and ethyl 2,3,4-tri-O-benzyl-1-thio-b-D-
2
5
28
cals. They applied the Falck–Mioskowski procedure
in deuterated media in the presence of nucleophiles hav-
ing an OD group. Reaction proceeded via the oxonium
ion formed in the first protonation step of the glycal.
2
6b
2
6c
2
9
glucopyranoside (12) were prepared according to the

I. Wandzik, T. Bieg / Carbohydrate Research 341 (2006) 2702–2707
2705
1
3
published procedures. 4-O-Benzyl-3-O-tert-butyldimeth-
ylsilyl-L-rhamnal (4) was synthesised by benzylation of
(H-6a)). Selected
C NMR data: 138.84, 138.60
(PhCH a), 138.50, 138.45 (PhCH b), 97.28 (C-1b),
94.71 (C-1a), 37.53 (C-2b), 36.31 (C-2a), 18.24 (C-6b),
18.14 (C-6a). HRESIMS: Calcd for C H O Na
2
2
2
8
3
-O-tert-butyldimethylsilyl-L-rhamnal
with benzyl
bromide/NaH in DMF; 1,2-di-O-dodecanoyl-rac-gly-
cerol (9) was synthesised via debenzylation of 1-O-benz-
2
6
34
4
+
([M+Na] ): m/z 433.2355, found: m/z 433.2371.
3
0
yl-2,3-di-O-dodecanoyl-rac-glycerol in the presence of
a Pd(OH) /cyclohexene system. Other chemicals were
1.2.3. 2,3-Di-O-dodecanoylglyceryl 3,4-di-O-benzyl-2,6-
dideoxy-L-arabino-hexopyranoside (18). Product 18 as
an inseparable a,b-anomeric mixture was purified on a
column of silica gel using solvent system B as the eluent;
2
purchased from Aldrich and Fluka Chemical Compa-
nies and were used without purification. Solvents were
˚
dried and stored over molecular sieves (4 A) under an
1
inert atmosphere.
yield 59%, colourless syrup. H NMR: (a:b = 4.5:1)
0
7
.25–7.36 (m, PhCH ), 5.18 (m, H-2 ), 4.55–4.98 (m,
2
1
.2. Typical glycosylation procedure
PhCH ), 4.82, 4.84 (2br d, J 3.0 Hz, H-1a), 4.44 (m,
2
0 0 0
H-1b), 3.44–4.44 (m, H-3, H-5a, H-1 a, H-1 b, H-3 a,
0
To a solution of glycal 1, 2, 3 or 4 (0.3 mmol) and gly-
cosyl acceptors 5–12 (0.36 mmol) in dry CH Cl
H-3 b), 3.32 (m, H-5b), 3.11 (t, J 9.0 Hz, H-4), 2.22–
2.37 (m, CH in C H CO, H-2 ), 1.54–1.72 (m, CH
2
2
2
11 23
eq
2
(
2 mL), a catalytic amount of TPHB (0.03 mmol) was
in C H CO, H-2 ), 1.19–1.37 (m, CH in C H -
11 23 ax 2 11 23
added (Table 1). The mixture was stirred at room tem-
perature for 10 min to 6 h (appropriate reaction times
are given in Table 1). After completion (TLC, 8:1 tolu-
ene–EtOAc) the reaction mixture was concentrated to
give a crude product mixture that was purified directly
by column chromatography with an appropriate solvent
system as indicated.
CO, CH3 (H-6)), 0.83–0.92 (m, CH3 in C H CO).
11 23
1
3
Selected C NMR data: 173.37, 173.02 (C H CO),
1
1
23
138.60, 138.45 (PhCH ), 99.83, 99.61 (C-1b), 97.59,
2
97.23 (C-1a), 35.61, 35.51 (C-2b), 34.32, 34.13 (C-2a),
18.13 (C-6). ESIMS: Calcd for C H O Na
4
7
74
8
+
([M+Na] ): m/z 789.53, found: m/z 789.5.
1.2.4. Cyclohexyl 4-O-acetyl-3-O-tert-butyldimethylsilyl-
1
.2.1. Ethyl 3,4-di-O-benzyl-2,6-dideoxy-L-arabino-hexo-
2,6-dideoxy-L-arabino-hexopyranoside (21). Product 21
as an inseparable a,b-anomeric mixture was purified on
a column of silica gel using solvent system C as the
pyranoside (14). Product 14 as an inseparable a,b-ano-
meric mixture was purified on a column of silica gel
using solvent system B as the eluent; yield 81%, colour-
less syrup. H NMR: (a:b = 3:1) 7.22–7.36 (m, PhCH ),
1
eluent; yield 76%, colourless syrup. H NMR: (a:b = 4:1)
1
4.97 (d, J 3.2 Hz, H-1a), 4.63 (t, J 9.2 Hz, H-4), 4.60
(m, H-1b), 4.05 (ddd, J 5.3, 9.2, 11.2 Hz, H-3a), 3.80
(dq, J 6.3, 9.2 Hz, H-5a), 3.74 (m, H-3b). 3.64 (m,
C H b), 3.51 (m, C H a), 3.33 (m, H-5b), 2.06, 2.07
2
4
.56–4.98 (m, PhCH ), 4.86 (br d, J 3.2 Hz, H-1a), 4.41
2
(
dd, J 2.0, 9.8 Hz, H-1b), 3.97 (ddd, J 5.1, 8.8, 11.3, H-
a), 3.74 (dq, J 6.1, 9.2 Hz, H-5a), 3.27–3.71 (m,
CH CH , H-5b, H-3b). 3.13 (t, J 9.2 Hz, H-4), 2.34
3
6
11
6
11
(2s, CH CO), 2.06 (m, H-2 b), 1.99 (ddd, J ꢁ 0, 5.3,
2
3
3
eq
(
m, H-2 b), 2.29 (ddd, J 1.2, 5.1, 12.9 Hz, H-2 a),
20 Hz, H-2 a), 1.22–1.88 (m, C H , H-2 ), 1.19 (d, J
eq 6 11 ax
eq
eq
1
.67 (ddd, J 3.2, 11.3, 12.9 Hz, H-2 a), 1.62 (m,
6.3 Hz, CH (H-6b)), 1.13 (d, J 6.3 Hz, CH (H-6a)),
3 3
ax
H-2 b), 1.33 (d, J 6.1 Hz, CH (H-6b)), 1.28 (d, J
0.85, (s, Si[C(CH ) (CH ) ]a), 0.84 (s, Si[C(CH ) -
3 3 3 2 3 3
ax
3
6
.1 Hz, CH (H-6a)), 1.22, 1.17 (2t, J 7.1 Hz, CH CH ).
(CH ) ]b), 0.06, 0.04 (2s, Si[C(CH ) (CH ) ]a), 0.05,
3 2 3 3 3 2
0.03 (2s, Si[C(CH ) (CH ) ]b). Selected C NMR data:
3 3 3 2
3
3
2
3
1
13
Selected C NMR data: 138.80, 138.62 (PhCH2),
9
1
9.31 (C-1b), 96.81 (C-1a), 37.10 (C-2b), 35.88 (C-2a),
8.17 (C-6), 15.16 (OCH CH b), 15.06 (OCH CH a).
170.06, 169.89 (CH COa, b), 97.09 (C-1b), 94.96 (C-1a),
3
41.07 (C-2b), 39.76 (C-2a), 25.59, 25.53 (Si[C(CH3)3-
(CH ) ]a, b), 21.20 (CH CO), 17.83 (Si[C(CH ) (CH ) ]),
2
3
2
3
+
HRESIMS: Calcd for C H O Na ([M+Na] ):
2
2
28
4
3 2
3
3 3
3 2
m/z 379.1885, found: m/z 379.1853.
17.79 (C-6b), 17.63 (C-6a), ꢀ4.56, ꢀ4.87 (Si[C(CH ) -
3
3
(
CH ) ]). HRESIMS: Calcd for C H O SiNa
3 2 20 38 5
+
1
.2.2. Cyclohexyl 3,4-di-O-benzyl-2,6-dideoxy-L-arabino-
([M+Na] ): m/z 409.2387, found: m/z 409.2395.
hexopyranoside (15). Product 15 as an inseparable a,b-
anomeric mixture was purified on a column of silica gel
1.2.5. Cholesteryl 4-O-acetyl-3-O-tert-butyldimethylsilyl-
2,6-dideoxy-L-arabino-hexopyranoside (22). Product 22
as an inseparable a,b-anomeric mixture was purified on
a column of silica gel using solvent system C as the elu-
using solvent system C as the eluent; yield 71%, colour-
1
less syrup. H NMR: (a:b = 4:1) 7.22–7.36 (m, PhCH ),
2
5
.01 (br d, J 2.7 Hz, H-1a), 4.53–4.98 (m, PhCH ), 4.54
2
1
(
dd, J 2.2, 9.8 Hz, H-1b), 3.99 (ddd, J 5.1, 9.0, 11.5, H-
a), 3.82 (dq, J 6.1, 9.0 Hz, H-5a), 3.56–3.68 (m,
C H b, H-3b). 3.51 (m, C H a), 3.32 (m, H-5b), 3.13
ent; yield 58%, colourless syrup. H NMR: (a:b = 4:1)
0
3
5.28–5.38 (m, H-6 ), 4.97 (d, J 2.9 Hz, H-1a), 4.55–
4.64 (m, H-1b), 4.62, 4.60 (2t, J 9.4 Hz, H-4a,b), 4.02
6
11
6
11
(
t, J 9.0 Hz, H-4b), 3.10 (t, J 9.0 Hz, H-4a), 2.30 (m,
(ddd, J 5.3, 9.0, 11.0 Hz, H-3a), 3.79 (dq, J 6.1,
0
H-2 b), 2.24 (ddd, J 1.2, 5.1, 13.0 Hz, H-2 a), 1.12
(
9.4 Hz, H-5a), 3.73 (m, H-3b), 3.55 (m, H-3 b), 3.26–
eq
eq
0
m, C H , CH (H-6b), H-2 ), 1.27 (d, J 6.1 Hz, CH
3.47 (m, H-3 a, H-5b), 0.80–2.45 (m, H-2 , H-2 ,
6
11
3
ax
3
eq
ax

2706
I. Wandzik, T. Bieg / Carbohydrate Research 341 (2006) 2702–2707
Si[C(CH ) (CH ) ], Si[C(CH ) (CH ) ], steryl-H) 2.06,
67.53, 67.18, 66.00, 65.49 (C-2, C-3, C-4, C-5, C-6, C-
3 , C-4 , C-5 ), 39.03 (C-2), 26.09, 25.97, 25.01, 24.38
3
3
3 2
3 3
3 2
0
0
0
2
.07 (2s, CH CO), 1.19 (d, J 6.1 Hz, CH (H-6b)), 1.11
3
3
0
(
d, J 6.1 Hz, CH (H-6a)), 1.01 (s, CH -19 ), 0.68 (s,
((CH ) C), 25.60 (Si[C(CH ) (CH ) ]), 21.19 (CH CO),
3
3
3 2
3 3
3 2
3
0
13
0
CH -18 ). Selected C NMR data: 170.26 (CH CO),
1
17.86 (Si[C(CH ) (CH ) ]), 17.56 (C-6 ), ꢀ4.50, ꢀ4.91
3
3
3 3
3 2
0
0
41.05, 140.89 (C-5 a, b), 122.01, 121.94 (C-6 a, b),
7.57 (C-1b), 95.53 (C-1a), 40.40 (C-2b) 39.94
(Si[C(CH ) (CH ) ]). HRESIMS: Calcd for C H O -
3 3 3 2 26 46 10
+
9
SiNa ([M+Na] ): m/z 569.2758, found: m/z 569.2732.
(
(
1
C-2a), 25.76, 25.81 (Si[C(CH ) (CH ) ]a, b), 21.30
3 3 3 2
0
CH CO), 18.96 (C-19 ), 18.04 (Si[C(CH ) (CH ) ]),
3 3 3 3 2
1.2.8. 4-O-Acetyl-3-O-tert-butyldimethylsilyl-2,6-dide-
0
7.84 (C-6), 12.08 (C-18 ), ꢀ4.20, ꢀ4.25, ꢀ4.63, ꢀ4.58
oxy-a-L-arabino-hexopyranosyl-(1!3)-1,2:5,6-di-O-iso-
propylidene-a-D-glucopyranose (26). Product 26 as
an inseparable a,b-anomeric mixture was purified on a
column of silica gel using solvent system A as the eluent;
(
Si[C(CH ) (CH ) ]). HRESIMS: Calcd for C H O -
3 3 3 2 41 72 5
+
SiNa ([M+Na] ): m/z 695.5047, found: m/z 659.5074.
1
1
.2.6. 2,3-Di-O-dodecanoylglyceryl 4-O-acetyl-3-O-tert-
butyldimethylsilyl-2,6-dideoxy-L-arabino-hexopyranoside
24). Product 24 as an inseparable a,b-anomeric mix-
yield 45%, colourless syrup. H NMR (a-anomer): 5.89
0
(d, 1H, J 3.8 Hz, H-1), 5.01 (d, 1H, J 3.5 Hz, H-1 ),
4.64 (t, 1H J 9.3 Hz, H-4 ), 4.50 (d, 1H, J 3.7 Hz, H-
0
(
ture was purified on a column of silica gel using solvent
3), 3.66–4.36 (m, 7H, H-2, H-4, H-5, H-6a, H-6b, H-
1
0
0
system B as the eluent; yield 63%, colourless syrup. H
3 , H-5 ), 2.05 (s, 3H, CH CO), 2.00 (ddd, 1H, J ꢁ 0,
3
0
0
NMR: (a-anomer) 5.21 (m, H-2 ), 4.80, 4.83 (2d, J
5.7, 13.5 Hz, H-2 ), 1.81 (ddd, 1H, J 3.5, 11.4,
13.5 Hz, H-2 ) 1.31, 1.36, 1.41, 1.51 (4s, 12H,
2(CH ) C), 1.10 (d, 3H J 6.1 Hz, CH (H-6 )), 0.85 (s,
eq
0
3
9
.5 Hz, H-1), 4.63 (t, J 9.3 Hz, H-4), 4.33 (ddd, J 3.8,
ax
0
0
.7, 11.6 Hz, H-3), 3.90–4.22 (m, H-3 a,b), 3.60–3.78
3
2
3
0
0
(
m, H-1 a, H-5), 3.45–3.56 (m, H-1 b), 2.26–2.36 (m,
9H, Si[C(CH ) (CH ) ]), 0.03, 0.05 (2s, 6H,
3 3 3 2
1
3
CH in C H CO), 2.07, 2.08 (2s, CH CO), 2.04 (m,
Si[C(CH ) (CH ) ]).
C NMR (a-anomer): 169.97
2
11 23
3
3 3
3 2
H-2 ), 1.74 (ddd, J 3.5, 11.6, 13.2 Hz, H-2 ), 1.55–
(CH CO), 111.93, 109.12, ((CH ) C), 105.36 (C-1),
eq
ax
3
3 2
0
1
.68 (m, CH2 in C H CO), 1.20–1.37 (m, CH in
94.26 (C-1 ), 81.79, 81.25, 77.55, 76.12, 72.07, 68.12,
11
23
2
0
0
0
C H CO), 1.13, 1.14 (2d, J 6.1 Hz, CH (H-6)), 0.80–
67.50, 66.30 (C-2, C-3, C-4, C-5, C-6, C-3 , C-4 , C-5 ),
1
1
23
3
0
0
1
9
.93 (m, CH in C H CO, Si[C(CH ) (CH ) ]), 0.03,
38.99 (C-2), 26.82, 26.72, 26.18, 25.30 ((CH ) C), 25.58
3
11 23
3 3
3 2
3 2
1
3
.04 (2s, Si[C(CH ) (CH ) ]). C NMR: (a-anomer)
(Si[C(CH ) (CH ) ]), 21.12 (CH CO), 17.85 (Si[C(CH ) -
3
3
3 2
3 3
3 2
3
3 3
0
73.60, 173.18 (C H CO), 170.21 (CH CO), 97.85,
(CH ) ]), 17.33 (C-6 ), ꢀ4.46, ꢀ4.88 (Si[C(CH ) (CH ) ]).
1
1
23
3
3 2
3 3
3 2
+
7.47 (C-1), 70.09, 69.83, 67.48, 66.46, 65.35, 62.65
HRESIMS: Calcd for C H O SiNa ([M+Na] ): m/z
26 46 10
0
0
0
(
C-3, C-4, C-5, C-1 , C-2 , C-3 ), 39.16, 39.09 (C-2),
569.2758, found: m/z 569.2746.
3
2
4.54, 34.34, 32.13, 29.84, 29.71, 29.56, 29.35, 25.18,
5.12, 22.90, 14.33 (C H CO), 25.77 (Si[C(CH ) -
1.2.9. Ethyl 4-O-acetyl-3-O-tert-butyldimethylsilyl-2,6-di-
deoxy-a-L-arabino-hexopyranosyl-(1!6)-2,3,4-tri-O-benz-
yl-1-thio-b-D-glucopyranoside (27). Product 27 was
purified on a column of silica gel using solvent system
1
1
23
3 3
(
CH ) ]), 21.36 (CH CO), 18.03 (Si[C(CH ) (CH ) ]),
3 2 3 3 3 3 2
1
7.84 (C-6), ꢀ4.32, ꢀ4.70 (Si[C(CH ) (CH ) ]). ESIMS:
3
3
3 2
+
Calcd for C H O SiNa ([M+Na] ): m/z 765.53,
4
1
78
9
found: m/z 765.5.
C as the eluent; yield 79%, colourless syrup; [a] ꢀ14.9
1
(
c 0.8, CHCl ) H NMR: 7.24–7.38 (m, 15H, PhCH ),
3
2
1
.2.7. 4-O-Acetyl-3-O-tert-butyldimethylsilyl-2,6-dide-
4.54–4.97 (m, 6H, PhCH ), 4.78 (d, 1H, J 3.4 Hz, H-
2
0
0
oxy-a-L-arabino-hexopyranosyl-(1!6)-1,2:3,4-di-O-iso-
propylidene-a-D-galactopyranose (25). Product 25
was purified on a column of silica gel using solvent sys-
1 ), 4.62 (t, 1H J 9.3 Hz, H-4 ), 4.47 (d, 1H, J 9.7 Hz,
0
H-1), 4.02 (ddd, 1H, J 5.5, 9.7, 11.3 Hz, H-3 ), 3.39–
0
3.91 (m, 7H, H-2, H-3, H-4, H-5, H-6a, H-6b, H-5 ),
tem A as the eluent; yield 78%, colourless syrup; [a]
2.75 (m, 2H, SCH CH ), 2.07 (s, 3H, CH CO), 2.01
2
3
3
1
0
eq
ꢀ
87.7 (c 1.1, CHCl ); H NMR: 5.53 (d, 1H, J 4.9 Hz,
(ddd, 1H, J ꢁ 0, 5.5, 12.9 Hz, H-2 ), 1.72 (ddd, 1H,
3
0
0
H-1), 4.90 (d, 1H, J 2.9 Hz, H-1 ), 4.63 (t, 1H J
J 3.4, 11.3, 12.9 Hz, H-2 ) 1.34 (t, 3H, J 9.3 Hz,
ax
0
0
9
.3 Hz, H-4 ), 4.62 (dd, 1H, J 2.4, 7.8 Hz, H-3), 4.32
SCH CH ), 1.12 (d, 3H J 6.3 Hz, CH (H-6 )), 0.85 (s,
2
3
3
(
dd, 1H, J 2.4, 4.9 Hz, H-2), 4.24 (dd, 1H, J 1.9,
9H, Si[C(CH ) (CH ) ]), 0.03, 0.04 (2s, 6H,
3
3
3 2
13
0
7
3
5
6
3
.8 Hz, H-4), 4.02 (ddd, 1H, J 5.4, 9.3, 11.2 Hz, H-3 ),
Si[C(CH ) (CH ) ]).
C
NMR: 170.00 (CH CO),
3
3
3 2
3
0
.97 (m, 1H, H-5), 3.80 (m, 1H, H-5 ), 3.77 (dd, 1H, J
138.30, 137.92, 128.49, 128.41, 128.27, 127.94, 127.89,
0
.9, 10.5 Hz, H-6a), 3.55 (dd, 1H, J 7.8, 10.5 Hz, H-
127.79 (CH Ph), 97.59 (C-1 ), 84.84 (C-1), 86.70,
2
0
0
b), 2.09 (ddd, 1H, J 1.2, 5.4, 13.3 Hz, H-2 ) 2.07 (s,
81.78, 78.59, 78.25 (C-2, C-3, C-4, C-5), 77.70 (C-4 ),
75.90, 75.49, 75.09 (CH Ph), 67.42 (C-3 ), 66.62 (C-5 ),
65.88 (C-6), 39.10 (C-2 ) 25.56, (Si[C(CH ) (CH ) ]),
eq
0
0
H, CH CO), 1.74 (ddd, 1H, J 2.9, 11.2, 13.3 Hz,
3
2
0
0
H-2 ), 1.34, 1.35, 1.44, 1.55 (4s, 12H, 2(CH ) C), 1.13
(
(
NMR: 170.03 (CH CO), 109.28, 108.60 ((CH ) C),
9
ax
3 2
3 3
3 2
0
d, 3H J 6.2 Hz, CH (H-6 )), 0.85 (s, 9H, Si[C(CH ) -
24.82 (SCH CH ), 21.16 (CH CO) 17.82 (Si[C(CH ) -
2 3 3 3 3
3
3 3
1
3
0
CH ) ]), 0.03, 0.05 (2s, 6H, Si[C(CH ) (CH ) ]).
C
(CH ) ]), 17.60 (C-6 ), 15.28 (SCH CH ), ꢀ4.50, ꢀ4.87
3
2
3 3
3 2
3 2
2
3
(Si[C(CH ) (CH ) ]). ESIMS: Calcd for C H O SSiNa
3 3 3 2 43 60 9
([M+Na] ): m/z 803.36, found: m/z 803.3.
3
3 2
0
+
7.22 (C-1 ), 96.24 (C-1), 77.78, 71.19, 70.67, 70.65,

I. Wandzik, T. Bieg / Carbohydrate Research 341 (2006) 2702–2707
2707
1
.2.10.
4-O-Benzyl-3-O-tert-butyldimethylsilyl-2,6-di-
3. Priebe, W.; Grynkiewicz, G. In From Glycoscience.
Chemistry and Chemical Biology; Fraser-Raid, B., Tatsua,
K., Thiem, J., Eds.; Springer: Berlin, 2001; pp 749–783.
deoxy-L-arabino-hexopyranosyl-(1!6)-1,2:3,4-di-O-iso-
propylidene-a-D-galactopyranose (28). Product 28 as an
inseparable a,b-anomeric mixture was purified on a col-
umn of silica gel using solvent system A as the eluent;
4
. Marzabadi, C. H.; Franck, R. W. Tetrahedron 2000, 56,
385–8417.
8
5. Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503–
1
yield 59%, colourless syrup. H NMR: (a:b = 5.5:1)
1531.
6
. Thorson, J. S.; Vogt, T. In Carbohydrate-Based Drug
Discovery; Wong, C.-H., Ed.; Wiley-VCH: Weinheim,
2003; Vol. 2, pp 685–711.
7
1
3
5
5
3
.26–7.34 (m, PhCH ), 5.51, 5.52 (2d, J 5.0 Hz, H-
a,b), 4.55–4.96 (m, PhCH , H-3), 4.86 (d, 1H, J
.3 Hz, H-1 a), 4.48 (m, H-1 b), 4.28, 4.33 (2dd, J 2.4,
.0, H-2a,b), 4.22 (dd, J 1.8, 7.9 Hz, H-4), 4.80 (ddd, J
2
2
0
0
7
. Pellissier, H. Tetrahedron 2005, 61, 2947–2993.
8. Toshima, K. Carbohydr. Res. 2006, 341, 1282–1297.
9. Zheng, C.; Seeberger, P. H.; Danishefsky, S. J. J. Org.
Chem. 1998, 63, 1126–1130.
10. Seeberger, P. H.; Beebe, X.; Sukenick, G. D.; Pochapsky,
S.; Danishefsky, S. J. Angew. Chem., Int. Ed. 1997, 36,
491–493.
0
.1, 8.9, 11.2 Hz, H-3 a), 3.66–4.44 (m, H-5, H-6a, H-
0
0
b, H-5 a), 3.51 (dd, J 7.0, 10.4 Hz, H-6b), 3.29 (m,
0
0
0
H-5 b), 2.99 (t, J 8.9 Hz, H-4 ) 2.15 (m, H-2 b) 2.07
eq
0
(
ddd, 1H, J ꢁ 0, 5.1, 13.2 Hz, H-2 a), 1.67 (ddd, 1H,
eq
0
0
ax
J 3.3, 11.2, 13.2 Hz, H-2 a), 1.64 (m, H-2 bÞ, 1.32,
11. Ferrier, R. J. Adv. Carbohydr. Chem. Biochem. 1969, 24,
199–266.
ax
1
6
0
1
.33, 1.43, 1.54 (4s, 2(CH ) C), 1.22, 1.28 (2d, J
3 2
0
.2 Hz, CH3 (H-6 a,b)), 0.91 (s, Si[C(CH ) (CH ) ]),
.08 (s, Si[C(CH ) (CH ) ]). Selected C NMR data:
38.69 (PhCH a), 138.37 (PhCH b), 109.24, 108.54
1
2. Bolitt, V.; Mioskowski, Ch.; Lee, S.-G.; Falck, J. R. J.
Org. Chem. 1990, 55, 5812–5813.
3 3
3 2
1
3
3
3
3 2
1
1
3. Sabesan, S.; Neira, S. J. Org. Chem. 1991, 56, 5468–5472.
4. Toshima, K.; Nagai, H.; Ushiki, Y.; Matsumura, S.
Synlett 1998, 1007–1009.
2
2
0
0
(
3
(CH ) C), 100.15 (C-1 b), 97.24 (C-1 a), 96.28 (C-1),
3 2
0 0
6.87 (C-2 a), 35.61 (C-2 b), 26.82, 26.72, 26.18, 25.30
15. Pachamuthu, K.; Vankar, Y. D. J. Org. Chem. 2001, 66,
511–7513.
7
(
(
(CH ) C), 25.57, 25.80 (Si[C(CH ) (CH ) ]a, b), 17.70
3 2 3 3 3 2
0 0
1
6. Yadav, J. S.; Reddy, B. V. S.; Bhaskar Reddy, K.;
Satyanarayana, M. Tetrahedron Lett. 2002, 43, 7009–7012.
7. Wardrop, D. J.; Zhang, W. Tetrahedron Lett. 2002, 43,
5389–5391.
C-6 b), 17.33 (C-6 a), 17.85 (Si[C(CH ) (CH ) ]),
3 3 3 2
ꢀ
4.46, ꢀ4.89 (Si[C(CH ) (CH ) ]). HRESIMS: Calcd
+
3
3
3 2
1
for C H O SiNa ([M+Na] ): m/z 617.3122, found:
3
1
50
9
m/z 617.3156.
18. Colinas, P. A.; Lieberknecht, A.; Bravo, R. D. Tetra-
hedron Lett. 2002, 43, 9065–9068.
1
9. Squarcia, A.; Marroni, S.; Piancatelli, G.; Passacantilli, P.
Tetrahedron: Asymmetry 2004, 15, 3769–3773.
0. McDonald, F. E.; Subba Reddy, K. Angew. Chem., Int.
Ed. 2001, 40, 3653–3655; McDonald, F. E.; Wu, M. Org.
Lett. 2002, 4, 3979–3981.
Acknowledgements
2
Financial support from the Polish State Committee for
Scientific Research (Grant No. 3 T09 A 01226) is grate-
fully acknowledged.
21. Wandzik, I.; Bugla, J.; Szeja, W. Chem. Phys. Lipids 2006,
39, 77–83.
2. Coleman, R. S.; Fraser, J. R. J. Org. Chem. 1993, 586,
58–392.
3. Renneberg, B.; Li, Y.-M.; Laatsch, H.; Fiebig, H.-H.
Carbohydr. Res. 2000, 329, 861–872.
1
2
2
2
3
Supplementary data
4. Wandzik, I.; Szeja, W. Pol. J. Chem. 1999, 73, 1163–1170.
25. Kaila, N.; Blumenstein, M.; Bielawska, H.; Franck, R. W.
1
13
Supplementary data (copies of H and C NMR spectra
of compounds 13–28) associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
J. Org. Chem. 1992, 57, 4576–4578.
2
6. (a) Roth, W.; Pigman, W. Methods Carbohydr. Chem.
968, 2, 405; (b) Fletcher, H. G. Methods Carbohydr.
1
2
006.09.007.
Chem. 1968, 2, 226; (c) Schmidt, O. T. Methods Carbo-
hydr. Chem. 1968, 2, 321.
2
7. Chmielewski, M.; Fokt, I.; Grodner, J.; Grynkiewicz, G.;
Szeja, W. J. Carbohydr. Chem. 1989, 8, 735–741.
8. Thiem, J.; Klaffke, W.; Springer, D. Carbohydr. Res. 1988,
174, 201–210.
References
2
1
. Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed.
996, 35, 1380–1419.
. Bilodeau, M. T.; Danishefsky, S. J. In Modern Methods in
Carbohydrate Synthesis; Khan, S. H., O’Neill, R. A., Eds.;
Harwood Academic: Amsterdam, 1996; pp 171–193,
Chapter 8.
1
29. Saibal Kumar, D.; Nirmolemdu, R. J. Carbohydr. Chem.
1995, 14, 417–428.
30. Briggs, J. C.; Haines, A. H.; Taylor, R. J. K.; Dawson, A.
P.; Gibson, I.; Hook, J.; Lloyd, A.; Meiners, S. Carbohydr.
Res. 1992, 234, 23–35.
2