Regio- and stereoselectivity in preparation of 2-deoxysugar glycoglycerolipid derivatives evaluated by high resolution 1H NMR

Article abstract of DOI:10.1016/j.chemphyslip.2005.09.002

New glycoglycerolipids, derivatives of 2-deoxysugars bearing one or two fatty acid chains have been synthesised. Various levels of regio- and stereoselectivity have been attained for the triphenylphosphine hydrobromide (TPHB) catalysed addition of the glycerol moiety to some representative glycals. The influence of the structure of glycal derivatives in glycosylation reactions is discussed.

Full text of DOI:10.1016/j.chemphyslip.2005.09.002

Chemistry and Physics of Lipids 139 (2006) 77–83
Short communication
Regio- and stereoselectivity in preparation of 2-deoxysugar
glycoglycerolipid derivatives evaluated by high
1
resolution H NMR
∗
Ilona Wandzik , Joanna Bugla, Wiesław Szeja
Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry,
Silesian University of Technology, 44-100 Gliwice, Krzywoustego 4, Poland
Received 13 September 2004; received in revised form 19 September 2005; accepted 19 September 2005
Available online 11 October 2005
Abstract
New glycoglycerolipids, derivatives of 2-deoxysugars bearing one or two fatty acid chains have been synthesised. Various levels
of regio- and stereoselectivity have been attained for the triphenylphosphine hydrobromide (TPHB) catalysed addition of the
glycerol moiety to some representative glycals. The influence of the structure of glycal derivatives in glycosylation reactions is
discussed.
©
2005 Elsevier Ireland Ltd. All rights reserved.
Keywords: Synthesis; Glycoglycerolipids; 2-Deoxyglycosides; Glycosylation
1
. Introduction
logues of d-galactose and d-glucose diacyl esters are
most abundant substances known to have an effect on
the immune system of mammals. However, derivatives
of 2-deoxy-d-glucose or 2-deoxy-l-rhamnose are also
found in bacterial lipids as the terminal monosaccha-
rides (Rivi e` re et al., 1987). Isolation of these compounds
from natural sources is very tedious owing to their low
concentration and the fact that they are often extracted
as mixtures of homologues. As studies on biological
activity require various glycolipids in pure state, we
decided to carry out experiments aiming at the synthe-
sis of glycoglycerolipids precursors as 2-deoxy sugar
derivatives. An increasing number of new glycoglyc-
erolipids containing one or two residues of fatty acids
has been reported in the literature (Holst, 2001). In this
work, we planned to synthesise a series of glycosylglyc-
erols in which hexanoyl and octadecanoyl moieties play
the role of medium and short fatty acid residues. Two
synthetic approaches were explored. The first approach
Glycolipids are glycoconjugates widely occurring in
bacteria, plants and animals. They serve a variety of
functions in nature. Glycoglycerolipids are one of a
class of glycolipids that are common constituents of
plant cell membranes and bacterial cell walls. As they
consist of one or more monosaccharide units and fatty
acid residues bound together through glycerol, they
have amphiphilic properties. The nature of the carbo-
hydrate moiety of glycosylglycerols has an influence
on various biologically significant activities (Larsen et
al., 2003; Janwitayanuchit et al., 2003; Colombo et al.,
2
002; Lindberg et al., 2002; Nakata, 2000; Nakata et
al., 2000; Marino-Albernas et al., 1996). Natural ana-
∗
Corresponding author.
E-mail address: ilona.wandzik@polsl.pl (I. Wandzik).
0
009-3084/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.chemphyslip.2005.09.002

7
8
I. Wandzik et al. / Chemistry and Physics of Lipids 139 (2006) 77–83
involved glycosylation of a racemic glycerol component
and investigation of α/β stereoselectivity of that reaction
as a function of the monosaccharide moiety structure
2.1.1.1. 1-O-benzyl-3-O-(3,4-di-O-benzyl-2,6-dideo
xy-l-arabino-hexopyranosyl)-glycerol (6A) and 1-O-
benzyl-2-O-(3,4-di-O-benzyl-2,6-dideoxy-l-arabino-
hexopyranosyl)-glycerol (6B). Products were purified
on a column of silica gel using solvent system A as an
(
Scheme 2). The second approach involved glycosyla-
tion of an optically active acylated glycerol component
Scheme 3). In series of experiments, we have chosen
1
(
eluent; yield 64%, colourless syrup; H NMR: δ = 1.27
ꢀ
selectively protected glycals, derivatives of l-rhamnal,
d-glucal and d-galactal, as sugar components.
and 1.30 (2d, J6
ꢀ
ꢀ
= 6.1 Hz, CH3 (H-6 )), 1.55–1.76
,5
ꢀ
ꢀ
(m, H-2 ax), 2.24–2.40 (m, H-2 eq), 2.56 and 2.66 (2bs,
ꢀ
ꢀ
= 9.2 Hz, H-4 α),
4 ,3
2
OH), 3.13 (dd, J4
ꢀ
ꢀ
= 9.0 Hz, J
ꢀ
,5
ꢀ
ꢀ
2
. Material and methods
3.14 (dd, J4
5
ꢀ
ꢀ
= 8.8 Hz, H-4 β), 3.30–4.00 (m, H-3 ,
, 1a, 1b, 2, 3a, 3b), 4.41 (m, H-1 β), 4.50–4.96 (m,
,5
ꢀ
ꢀ
1H NMR spectra were recorded in CDCl3 (internal
3PhCH2), 4.85 (bd, J1
= 3.6 Hz, H-1 α in 6A),
ꢀ
ꢀ
ꢀ
2 ax
ꢀ
= 2.4 Hz, H-1 α in 6B), 7.20–7.40 (m,
2 ax
TMS) with a Varian spectrometer at 300 MHz. In the
5.06 (bd, J1
3PhCH2).
ꢀ
ꢀ
ꢀ
ꢀ
assignments of the spectra protons H-1 –H-6 refer to
protons connected to the glycal ring moiety, whereas
protons 1a, 1b, 2, 3a and 3b refer to the various glycerol
protons. Optical rotations were measured with a Perkin-
Elmer 141 polarimeter using sodium lamp (589 nm) at
room temperature. Column chromatography was per-
formed on silica gel 60 (70–230 mesh, Merck) developed
with hexane–ethyl acetate solvent system: A, 5:1; B,
2.1.1.2. 1-O-octadecanoyl-3-O-(3,4-di-O-benzyl-2,6-
dideoxy-l-arabino-hexopyranosyl)-glycerol (7A) and
1-O-octadecanoyl-2-O-(3,4-di-O-benzyl-2,6-dideoxy-
l-arabino-hexopyranosyl)-glycerol
(7B). Products
were purified on a column of silica gel using solvent
system A as an eluent; yield 60%, colourless syrup;
1
1
0:1; C, 15:1 (v/v). Reactions were monitored by TLC
H NMR: δ = 0.85–0.90 (m, CH3 in C17H35CO),
ꢀ
on precoated plates of silica gel G (Merck), compo-
nents were detected by spraying the plates with 10%
sulphuric acid in ethanol followed by heating. All evap-
1.20–1.35 (m, 14CH2 in C17H35CO, CH3 (H-6 )),
1.56–1.77 (m, CH2 in C17H35CO, H-2 ax), 2.26–2.35
(m, CH2 in C17H35CO, H-2 eq), 3.13 (dd, J
J4
3a, 3b), 4.37–4.46 (m, H-1 β), 4.58–4.98 (m, 2PhCH2),
4.86 (bd, J1
J1
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
= 9.0 Hz,
4
,5
ꢀ
ꢀ
orations were performed under diminished pressure at
ꢀ
ꢀ
= 9.2 Hz, H-4 ), 3.30–4.70 (m, H-3 , 5 , 1a, 1b, 2,
,3
◦
ꢀ
5
0 C.
ꢀ
Perbenzylated glycals 1a, 2 and 3 (Chmielewski et
al., 1989), 3-O-silylated derivatives of l-rhamnal 1b,
c (Thiem et al., 1988), 1-O-benzyl-2,3-di-O-octanoyl-
ꢀ
ꢀ
= 2.9 Hz, H-1 α in 7A), 5.05 (bd,
,2 ax
ꢀ
=2.7 Hz, H-1 α in 7B), 7.20–7.40 (m, 2PhCH2).
,2 ax
ꢀ
ꢀ
1
rac-glycerol (Briggs et al., 1992) and 1-O-benzyl-2-
O-octanoyl-sn-glycerol 5 (Bugla et al., 2005) were
prepared according to the published procedures. 1-O-
octadecanoyl-rac-glycerol 4b and other chemicals were
purchased from Aldrich and Fluka and were used with-
out purification. Solvents were dried before use.
2.1.1.3. 1-O-benzyl-3-O-(4-O-acetyl-3-O-
tert-butyldimethylsilyl-2,6-dideoxy-l-arabino-
hexopyranosyl)-glycerol (8A) and 1-O-benzyl-2-O-
(4-O-acetyl-3-O-tert-butyldimethylsilyl-2,6-dideoxy-
l-arabino-hexopyranosyl)-glycerol
(8B). Products
were purified on a column of silica gel using solvent
system B as an eluent; yield 54%, colourless syrup; H
1
2
.1. Synthesis procedures and assignment of
NMR: δ = 0.03 and 0.04 (2s, 2CH3), 0.82 (s, (CH3)3C),
1
ꢀ
high-resolution H NMR spectra
1.10–1.22 (m, CH3 (H-6 )), 1.72 (ddd, J2
ꢀ
ꢀ
ꢀ
= 3.5 Hz,
ax,1
J2
ꢀ
ꢀ
= 9.5 Hz, J
ꢀ
ꢀ
= 11.2 Hz, H-2 ax), 2.07 (s,
ax,3
2 ax,2eq
ꢀ
2
.1.1. General method for the addition of racemic
CH3CO), 2.54 and 2.69 (2bs, 2OH), 3.40–4.10 (m, H-6 ,
5 1a, 1b, 2, 3a, 3b), 4.44–4.51 (m, H-1 β), 4.54–4.58 (m,
PhCH2, H-4 ), 4.81–4.86 (m, H-1 α in 8A), 5.01–5.06
ꢀ
ꢀ
glycerol component to glycals
ꢀ
ꢀ
To a solution of glycal 1a, 1b or 1c (0.3 mmol) and
glycerol component 4a, 4b or 4c (0.36 mmol) in dry
CH2Cl2 (2 ml), a catalytic amount of TPHB (0.03 mmol)
was added. The mixture was stirred at room temperature
for 30–60 min. Then, the reaction mixture was diluted
with CH2Cl2 (20 ml), washed with water (2 × 15 ml),
dried over anhydrous MgSO4 and concentrated to give
crude product mixture, which was subsequently purified
by column chromatography using an appropriate solvent
system as indicated.
ꢀ
(m, H-1 α in 8B), 7.22–7.40 (m, PhCH2).
2.1.1.4. 1-O-octadecanoyl-3-O-(4-O-acetyl-3-
O-tert-butyldimethylsilyl-2,6-dideoxy-l-arabino-
hexopyranosyl)-glycerol (9A) and 1-O-octadecanoyl-2-
O-(4-O-acetyl-3-O-tert-butyldimethylsilyl-2,6-dideoxy-
l-arabino-hexopyranosyl)-glycerol
(9B). Products
were purified on a column of silica gel using solvent
1
system B as an eluent; yield 32%, cream solid; H

I. Wandzik et al. / Chemistry and Physics of Lipids 139 (2006) 77–83
79
NMR: δ = 0.04 and 0.07 (2s, 2CH3), 0.82–0.93 (m,
CH3)3C), CH3 in C17H CO), 1.20–1.34 (m, 14CH2
3a, 3b), 4.37–4.46 (m, H-1β), 4.58–4.98 (m, 2PhCH2),
ꢀ
= 2.9 Hz, H-1 α in 12A), 5.05
1 ,2 ax
(
4.83 and 4.85 (2d, J
ꢀ
ꢀ
35
ꢀ
ꢀ
= 2.7 Hz, H-1 α in 12B), 5.18 (m, H-2),
1 ,2 ax
in C17H CO, CH3 (H-6 )), 1.54–1.80 (m, CH2 in
(2bd, J
ꢀ
ꢀ
3
5
ꢀ
ꢀ
C17H CO, H-2 ax), 1.97–2.13 (m, CH3CO, H-2 eq),
7.20–7.40 (m, 2PhCH2).
3
5
ꢀ
.25–2.40 (m, CH2 in C17H CO), 3.34–4.40 (m, H-3 ,
35
2
5
(
ꢀ
ꢀ
, 1a, 1b, 2, 3a, 3b), 4.56–4.72 (m, H-4 ), 4.82 and 4.84
2.1.2. General method for the addition of
ꢀ
ꢀ
2d, J1
ꢀ
ꢀ
= H-1 α in 9A), 5.05 and 5.11 (2m, H-1 α in
1-O-benzyl-2-O-octanoyl-sn-glycerol 5 to glycals
To a solution of glycal 1a, 1b, 2 or 3 (0.3 mmol)
and glycerol 5 (0.36 mmol) in dry CH2Cl2 (2 ml) a cat-
alytic amount of TPHB (0.03 mmol) was added. The
mixture was stirred at room temperature for 45 min.
Then, the reaction mixture was diluted with CH2Cl2
(20 ml), washed with water (2 × 15 ml), dried over anhy-
drous MgSO4 and concentrated to give the crude product
mixture, which was subsequently purified by column
chromatography using solvent system C as an eluent.
,2 ax
9
B).
2
.1.1.5. 1-O-benzyl-3-O-(4-O-acetyl-3-O-
tert-butyldiphenylsilyl-2,6-dideoxy-l-arabino-
hexopyranosyl)-glycerol (10A) and 1-O-benzyl-2-
O-(4-O-acetyl-3-O-tert-butyldiphenylsilyl-2,6-dideoxy-
l-arabino-hexopyranosyl)-glycerol
(10B). Products
were purified on a column of silica gel using solvent
system B as an eluent; yield 59%, colourless syrup;
1
H NMR: δ = 1.02 (s, (CH3)3C), 1.09 and 1.16 (2d,
ꢀ
ꢀ
ꢀ
J6
ꢀ
ꢀ
= 6.2 Hz, CH3 (H-6 )), 1.64–1.80 (m, H-2 ax, 2 eq),
2.1.2.1. 1-O-benzyl-2-O-octanoyl-3-O-(3,4-di-O-
benzyl-2,6-dideoxy-l-arabino-hexopyranosyl)-
sn-glycerol (13). Yield 85%, colourless syrup;
,5
1
3
J3
.90 (s, CH3CO), 2.18 and 2.29 (2d, J =5.0 Hz, 2OH),
ꢀ
.18–3.38 (m, H-5 , 1a, 1b, 2, 3a, 3b), 4.09 (ddd,
ꢀ
◦
1
ꢀ
ꢀ
= 5.3 Hz, J
ꢀ
ꢀ
= 9.9 Hz, J
ꢀ
ꢀ
= 9.7 Hz, H-3 ),
[α] = −35.0 (CHCl3, c = 1.3); H NMR: δ = 0.83–0.90
,2 eq
3 ,4
3 ,2 ax
ꢀ
ꢀ
4
.18–4.25 (m, H-1 β), 4.48 (s, PhCH2), 4.66 (bs, H-1 α
(m, CH3 in C7H CO), 1.20–1.38 (m, 4CH2 in
C7H CO, CH3 (H-6 )), 1.56–1.71 (m, CH2 in
C7H CO, H-2 ax), 2.18–2.36 (m, CH2 in C7H CO,
H-2 eq), 3.10 (dd, J
4 ), 3.50–4.02 (H-3 , 5 , 1a, 1b, 3a, 3b), 4.40 (dd,
=2.2 Hz,
(m, 3PhCH2), 4.84 (d, J1
15
ꢀ
ꢀ
in 10A), 4.79 (dd, J4
4
ꢀ
ꢀ
= 9.3 Hz, J
ꢀ
ꢀ
= 9.5 Hz, H-4 ),
,5
4 ,3
15
ꢀ
ꢀ
.90 (m, H-1 α in 10B), 7.20–7.70 (m, 2Ph, PhCH2).
15
15
ꢀ
ꢀ
ꢀ
= 9.0 Hz, J = 9.0 Hz, H-
ꢀ ꢀ
4
,5
4 ,3
ꢀ
ꢀ
ꢀ
2
.1.1.6. 1-O-octadecanoyl-3-O-(4-O-acetyl-3-
ꢀ
O-tert-butyldiphenylsilyl-2,6-dideoxy-l-arabino-
hexopyranosyl)-glycerol (11A) and 1-O-octadecanoyl-
J1
ꢀ
ꢀ
J
ꢀ ꢀ
= 9.5 Hz, H-1 β), 4.46–4.62
,2 eq
1 ,2 ax
ꢀ
= 2.9 Hz, H-1 α), 5.19
,2 ax
ꢀ
ꢀ
2
-O-(4-O-acetyl-3-O-tert-butyldiphenylsilyl-2,6-
(tt, J2,3 = 5.0 Hz, J2,1 = 5.0 Hz, H-2), 7.20–7.40 (m,
3PhCH2).
dideoxy-l-arabino-hexopyranosyl)-glycerol
(11B).
Products were purified on a column of silica gel using
solvent system B as an eluent; yield 27%, colourless
2.1.2.2. 1-O-benzyl-2-O-octanoyl-3-O-(4-O-acetyl-
3-O-tert-butyldimethylsilyl-2,6-dideoxy-l-arabino-
hexopyranosyl)-sn-glycerol (14). Yield 55%, colourless
syrup; [α] = −51.1 (CHCl3, c = 0.7); 1H NMR (α
anomer): δ = 0.03 and 0.04 (2s, 2CH3), 0.85 (s,
1
syrup; H NMR: δ = 0.83–0.92 (m, CH3 in C17H CO),
35
1
.02 (s, (CH3)3C), 1.06–1.34 (m, 14CH2 in C17H CO,
35
ꢀ
ꢀ
◦
CH3 (H-6 )), 1.52–1.72 (m, CH2 in C17H CO, H-2 ax),
35
2
.08 (s, CH3CO), 2.14–2.36 (m, CH2 in C17H CO,
35
ꢀ
ꢀ
ꢀ
H-2 eq), 3.16–4.18 (m, H-3 , 5 , 1a, 1b, 2, 3a, 3b),
4
J4
(CH3)3C), 0.88 (t, J = 6.6 Hz, CH3 in C7H CO), 1.12
15
ꢀ
ꢀ
ꢀ
(d, J6 = 6.3 Hz, CH3 (H-6 )), 1.24–1.26 (m, 4CH2 in
ꢀ ꢀ
,5
.16–4.26 (m, H-1 β) 4.67 (bs, H-1 α in 11A), 4.81 (dd,
ꢀ
ꢀ
ꢀ
ꢀ
= 9.3 Hz, J
ꢀ
ꢀ
= 9.2 Hz, H-4 ), 4.89 (m, H-1 α in
C7H CO), 1.60–1.68 (m, CH2 in C7H CO), 1.71 (ddd,
,5
4 ,3
15
15
1
1B), 7.30–7.70 (m, 2Ph).
J
2
J2
ꢀ
ꢀ
= 3.2 Hz, J
ꢀ
ꢀ
= 10.8 Hz, J
ꢀ
= 13.5 Hz, H-
2
ax,1
2 ax,3
2 ax,eq
ꢀ
ax), 1.98 (ddd, J2
ꢀ
ꢀ
ꢀ
= 1.0 Hz,
J
ꢀ
ꢀ
= 5.3 Hz,
eq,1
2 eq,3
ꢀ
= 13.5 Hz, H-2 eq), 2.06 (s, CH3CO), 2.34
ax,eq
2
.1.1.7. 2,3-di-O-octanoyl-1-O-(3,4-di-O-benzyl-2,6-
dideoxy-l-arabino-hexopyranosyl)-glycerol (12A) and
,3-di-O-octanoyl-2-O-(3,4-di-O-benzyl-2,6-dideoxy-
l-arabino-hexopyranosyl)-glycerol (12B). Products
were purified on a column of silica gel using solvent
system C as an eluent; yield 52%, colourless syrup;
(t, J = 7.5 Hz, CH2 in C7H CO), 3.50–3.80 (m,
15
ꢀ
1
H-5 , 1a, 1b, 3a, 3b), 3.97 (ddd, J
ꢀ
ꢀ
= 5.3 Hz,
2 eq
3
,
ꢀ
= 10.8 Hz, H-3 ), 4.57 and 4.95
3 , 2 ax
J3
ꢀ
ꢀ
= 9.5 Hz, J
ꢀ
ꢀ
,4
(qAB, J = 12.2 Hz, PhCH2), 4.62 (dd, J4
ꢀ
ꢀ
= 9.5 Hz,
,5
ꢀ
ꢀ
= 3,2 Hz, H-1 ),
1 , 2 ax
J4
ꢀ
ꢀ
= 9.5 Hz, H-4 ), 4.81 (d, J
ꢀ
ꢀ
,3
1
H NMR: δ = 0.83–0.92 (m, 2CH3 in C7H CO),
5.21 (m, H-2), 7.30–7.40 (m, PhCH2).
1
5
ꢀ
.20–1.35 (m, 8CH2 in C7H CO, CH3 (H-6 )),
15
1
1
ꢀ
.55–1.70 (m, 2CH2 in C7H CO, H-2 ax), 2.22–2.37
2.1.2.3. 1-O-benzyl-2-O-octanoyl-3-O-(3,4,6-tri-O-
15
ꢀ
(m, 2CH2 in C7H CO, H-2 eq), 3.12 (dd, J = 8.9 Hz,
ꢀ ꢀ
benzyl-2-deoxy-d-arabino-hexopyranosyl)-sn-glycerol
15
ꢀ
4 ,5
ꢀ
ꢀ
◦
(15). Yield 78%, colourless syrup [α] = +36.8 (CHCl3,
J4
ꢀ
ꢀ
= 8.9 Hz, H-4 ), 3.30–4.37 (m, H-3 , 5 , 1a, 1b,
,3

8
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I. Wandzik et al. / Chemistry and Physics of Lipids 139 (2006) 77–83
1
TPHB is applied to catalyse the addition of a glyc-
erol moiety to various glycals. In our study, selectively
protected l-rhamnal, d-glucal and d-galactal derivatives
were used.
c = 1.0); H NMR: δ = 0.83–0.90 (m, CH3 in C7H CO),
15
ꢀ
.20–1.38 (m, 4CH2 in C7H CO, CH3 (H-6 )),
15
1
1
ꢀ
.56–1.74 (m, CH2 in C7H CO, H-2 ax), 2.18–2.36
15
ꢀ ꢀ
m, CH2 in C7H CO, H-2 eq), 3.44–4.00 (m, H-3 , 4;
15
(
5
ꢀ
ꢀ
ꢀ
ꢀ
Constructionoftheglycerolmoietyhasbeenexplored
using commercially available isopropylideneglycerol
that was transformed via benzyl derivative to desired
starting materials 4a and 4c (Scheme 1). Optically
active glycerol derivative 5 has been prepared by enzy-
matic hydrolysis of 1-O-benzyl-2,3-di-O-octanoyl-rac-
glycerol catalysed by Novozyme 435 lipase in hexane as
a solvent (Bugla et al., 2005). The reaction was regios-
elective towards the primary acyl group and afforded
chiral derivative 5 highly enantioselectively (ee > 95%).
We, initially, examined the glycosylation of various
glycals with small excess (1.2 equiv.) of racemic 1-O-
benzyl-rac-glycerol 4a in the presence of TPHB (10%)
as a catalyst and CH2Cl2 as a solvent at room temper-
ature (Scheme 2). As could be expected, a complicated
isomeric mixture was formed in each glycosylation reac-
tion. First of all two regioisomers, A and B, might form
as a result of glycosylation since the glycerol moiety
in 4a possesses two free hydroxyl groups. Next, each
regioisomer A and B might constitute a mixture of two
diastereoisomeric α and β anomers of the glycal. More-
over, the glycerol moiety possesses a stereogenic centre
at C-2. Hence, the final reaction mixture might com-
pose eight isomers. First, glycosylation of 1a with 4a
as an acceptor showed low regio- and stereoselectivity
favouringtheαanomerandregioisomerA(Table1, entry
1). Detailed studies have elucidated the effect of vari-
ous protection groups at the C-3 position in l-rhamnal
on the regio- and stereoselectivity. We have used 3,4-
di-O-benzyl-l-rhamnal (1a), and rhamnal derivatives
with a bulky group at C-3 position: t-butyldimethylsilyl
(TBDMS) and t-butyldiphenylsilyl (TBDPS), 1b and 1c,
respectively. Thus, the glycosylations of 1a, 1b and 1c
with 1-O-benzyl-rac-glycerol, 4a proceeded effectively
, 6 a, 6 b, 1a, 1b, 3a, 3b), 4.40 (m, H-1 β), 4.40–4.90
ꢀ
(
m, 4PhCH2), 4.92 (d, J1
m, H-2), 7.15–7.40 (m, 4PhCH2).
ꢀ
ꢀ
= 2.7 Hz, H-1 α), 5.15
, 2 ax
(
2
.1.2.4. 1-O-benzyl-2-O-octanoyl-3-O-(3,4,6-tri-
O-benzyl-2-deoxy-d-lyxo-hexopyranosyl)-sn-glycerol
◦
(
16). Yield 72%, colourless syrup; [α] = +30.1 (CHCl3,
1
c = 1.4); H NMR (α anomer): δ = 0.83–0.90 (m, CH3
in C7H CO), 1.20–1.38 (m, 4CH2 in C7H CO, CH3
1
5
15
ꢀ
H-6 )), 1.56–1.66 (m, CH2 in C7H CO), 1.94 (dd,
15
(
J2
J2
ꢀ
= 12.6 Hz, H-2 eq), 2.00 (ddd,
2 eq,ax
ꢀ
ꢀ
= 4.4 Hz, J
= 3.6 Hz,
ꢀ
eq,3
ꢀ
ꢀ
J
ꢀ
ꢀ
= 10.2 Hz,
J
ꢀ
= 12.6 Hz,
2 ax,eq
ax,1
2 ax,3
ꢀ
H-2 ax), 2.26–2.36 (m, CH2 in C7H CO), 3.48–3.64
and 3.74–3.96 (2m, H-3 , 4 , 5 , 6 a, 6 b, 1a, 1b, 3a,
b), 4.40–4.90 (m, 4PhCH2), 4.89 (d, J
H-1 ), 5.18 (m, H-2), 7.15–7.40 (m, 4PhCH2).
15
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
= 2,7 Hz,
1
, 2 ax
ꢀ
3
. Results and discussion
Many methods have been developed for the prepara-
tion of 2-deoxy-␣-glycosides. Among them, one feasible
way is the use of glycals as glycosyl donors (Danishefsky
andBilodeau, 1996;MarzabadiandFranck, 2000;Priebe
and Grynkiewicz, 2001). A few new methods have been
reported so far for the direct synthesis of 2-deoxy-␣-
glycosides from glycals by addition of an alcohol. These
reactions are catalysed under mild conditions by, for
instance TPHB (Bolitt et al., 1990), cation-exchange
resin AG 50WX2 (Sabesan and Neira, 1991), BCl3,
BBr3 (Toshima et al., 1998), CAN (Pachamuthu and
Vankar, 2001) or CeCl3–NaI reagent system (Yadav et
al., 2002). The work described in this report is based on
the Falck–Mioskowski route (Bolitt et al., 1990) where
Scheme 1.

I. Wandzik et al. / Chemistry and Physics of Lipids 139 (2006) 77–83
81
Scheme 2.
Table 1
5). The results show that the best yields were achieved
when 3,4-di-O-benzyl-l-rhamnal was the starting mate-
rial, however, regioselectivity as well as stereoselectivity
were only moderate.
Addition of racemic glycerol component to glycals
Entry Donor Acceptor Yield (%) Product A:Ba
α:βb
1
2
3
4
5
6
7
1a
1a
1b
1b
1c
1c
1a
4a
4b
4a
4b
4a
4b
4c
64
60
54
32
59
27
52
6A:6B 6:1
7A:7B 2,5:1
8A:8B 5:1
3:1
3:1
12:1
1:0
5:1
1:0
5:1
Separation of regioisomers as well as stereoisomers
by column chromatography was not possible. The ratios
of regioisomers (product A:B) and stereoisomers (α:β)
9A:9B 1:1
10A:10B 10:1
11A:11B 3:1
12A:12B 10:1c
1
were determined by examination of the H NMR spec-
tra of isomer mixtures (for details, see the experimental
part). For the major C-1-O-glycosylated regioisomers
a
The ratio of regioisomers isolated by column chromatography was
ꢀ
(
products in series A) the H-1 α protons resonated at
1
determined by close examination of the H NMR spectra of the mixture
of regioisomers.
ꢀ
higher field than the H-1 α protons in the minor C-2-
O-glycosylated regioisomers (products in series B). For
example, H-1 α in 6A gave a doublet at δ = 4.85 ppm,
b
α:β ratio as a sum determined together in regioisomers A and B.
Regioisomer 12B was determined due to acyl group migration
c
ꢀ
under the reaction conditions.
while in 6B the corresponding doublet was observed at
ꢀ
δ = 5.06 ppm. H-1 β signals were observed as a multiplet
to afford the predominant 2-deoxy-␣-glycosides. In fur-
ther experiments, we employed glycerol derivatives with
medium and short fatty acid residues: octadecanoyl in 4b
and octanoyl in 4c (Scheme 2).
The results summarised in Table 1 illustrate that it
was possible to attain some level of regio- and stereose-
lectivity for the derivatives examined in this programme
with all cases favouring the α anomer and all except one
the A regioisomer. For example, the best ␣-selectivity
was achieved for glycals 1b and 1c treated with 4b as
an acceptor (entry 4,6). These transformations, however,
were not regioselective. Notably, excellent regioselectiv-
ity was obtained for glycal 1c in reaction with 4a (entry
at lower field, δ = 4.41 ppm. Thus, ratios of regioisomers
A:B and diastereoisomers α:β were easily determined
by H NMR.
1
We then focussed our attention on the use of opti-
cally active 1-O-benzyl-2-O-octanoyl-sn-glycerol 5 as
anacceptor. Accordingly, glycosylationofdonors1a, 1b,
2 and 3 was carried out (Scheme 3). This resulted in a sin-
gle regioisomer since this time no acyl migrations took
place and, therefore, only two diastereoisomers α and β
were formed. Thus, we have synthesised the 2-deoxy-
␣-glycosides predominantly in good yields as shown in
Table 2. The products were formed within 45 min and
were isolated as α/β mixtures. The α/β ratios were deter-
Table 2
Addition of 1-O-benzyl-2-O-octanoyl-sn-glycerol to glycals
2
3
α:βa
Entry
Donor
Acceptor
Product
Yield (%)
(α)
D
◦
◦
1
2
3
4
1a
1b
2
5
5
5
5
13
14
15
16
85
55
78
72
−35.0 (CHCl3, c = 1,3)
5:1
15:1
8:1
−51.1 (CHCl3, c = 0,7)
◦
◦
+36.8 (CHCl3, c = 1,0)
3
+30.1 (CHCl3, c = 1,4)
30:1
a
1
As determined by 300 MHz H NMR analysis.

8
2
I. Wandzik et al. / Chemistry and Physics of Lipids 139 (2006) 77–83
Scheme 3.
1
Chmielewski, M., Fokt, I., Grodner, J., Grynkiewicz, G., Szeja, W.,
989. An improved synthesis and NMR spectra of benzylated gly-
mined by H NMR (for details, see the experimental
1
part). For the ␤-glycosides the anomeric protons gave
double doublets with J1
between 2.0 and 2.2 Hz. The ␣-linked glycosides
gave a doublet with J1
stereoselectivity of the reaction was notably high when
the d-galactose derivative was employed. In this case,
almost pure α anomer was obtained (Table 2, entry 4).
Products 13–16 may be easily deprotected in the pres-
ence of Pd(OH)2/cyclohexene system to afford material
for biological studies.
cals. J. Carbohydr. Chem. 8 (5), 735–741.
ꢀ
ꢀ
between 9.5 and 10.0 Hz and
,2 ax
Colombo, D., Ronchetti, F., Toma, L., Pisano, B., Ianaro,
A., 2002. Inhibition of activated murine T-lymphocytes by
synthetic glycoglycerolipid analogues. Il Farmaco 57, 337–
J1
ꢀ
,2 eq
ꢀ
ꢀ
ꢀ
between 2.7 and 3.2 Hz. The
,2 ax
339.
Danishefsky, S.J., Bilodeau, M.T., 1996. Glycals in organic synthe-
sis: the evolution of comprehensive strategies for the assembly of
oligosaccharides and glycoconjugates of biological consequence.
Angew. Chem. Int. Ed. Engl. 35, 1380–1419.
Holst, O., 2001. Glycolipids. In: Fraser-Raid, B., Tatsua, K., Thiem,
J. (Eds.), From Glycoscience. Chemistry and Chemical Biology.
Springer-Verlag, Berlin, Heidelberg, pp. 2083–2106.
Janwitayanuchit, W., Suwanborirux, K., Patarapanich, Ch., Pumman-
gura, S., Lipipun, V., Vilaivan, T., 2003. Synthesis and anti-herpes
simplex viral activity of monoglycosyl diglycerides. Phytochem-
istry 64, 1253–1264.
Acknowledgement
Financial support of State Committee for Scientific
Research (KBN, grant 3 T09 A 13319) and Polpharma
Foundation (grant 011/2002) are gratefully acknowl-
edged.
Larsen, E., Kharazmi, A., Christensen, L.P., Christensen, S.B., 2003.
An antiinflammatory galactolipid from rose hip (Rosa Canina) that
inhibits chemotaxis of human peripheral blood neurophils in vitro.
J. Nat. Prod. 66, 994–995.
Lindberg, J., Svensson, S.C.T., P a˚ hlsson, P., Konradsson, P., 2002.
Synthesis of galactoglycerolipids found in the HT29 human colon
carcinoma cell line. Tetrahedron 58, 5109–5117.
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