Preparation of modified glycosyl glycerol derivatives by glycal rearrangement

Article abstract of DOI:10.1016/S0008-6215(98)00038-X

By Lewis acid catalysed allylic rearrangement reactions of various glycals with glycerol derivatives 2,3-unsaturated mono- and disaccharide glycosyl glycerol derivatives were obtained in good yields. A triglycosyl glycerol was successfully synthesized in a straightforward three step way from 3,4,6- tri-O-acetyl-1,5-anhydro-2-deoxy-D-arabino-hex-1-enitol.

Full text of DOI:10.1016/S0008-6215(98)00038-X

Carbohydrate Research 307 (1998) 263±270
Preparation of modi®ed glycosyl glycerol
derivatives by glycal rearrangement
Eusebius Wieczorek, Joachim Thiem *
InstitutfurOrganischeChemie,UniversitatHamburg,Martin-Luther-King-Platz6,D-20146Hamburg,
È
È
Germany
Received 29 September 1997; accepted 26 January 1998
Abstract
By Lewis acid catalysed allylic rearrangement reactions of various glycals with glycerol deriva-
tives 2,3-unsaturated mono- and disaccharide glycosyl glycerol derivatives were obtained in good
yields. A triglycosyl glycerol was successfully synthesized in a straightforward three step way from
3,4,6- tri-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-1-enitol. # 1998 Elsevier Science Ltd. All
rights reserved
Keywords: Ferrier reaction; Glycerol derivatives; Deoxy sugars
1. Introduction
By employment of the Ferrier reaction [4±6] with
1,2- or 1,3-protected glycerol derivatives as nucleo-
philes the formation of these modi®ed compounds
is possible in high yields. Thus, under allylic re-
arrangement glycals can be converted into the corre-
sponding 2,3-unsaturated glycosides by treatment
with nucleophiles in the presence of Lewis acids as
catalyst. In the present context, we have studied
this reaction with a variety of aglycons [7,8] as a way
of gaining easy access to modi®ed glycoconjugates.
Here, we wish to report on the synthesis of mod-
i®ed glycosyl glycerols under Ferrier conditions.
Glycosyl diacylglycerol derivatives are known as
major components of membrane lipids in a wide
variety of plants and microorganisms [1±3]. These
lipids consist of a polar carbohydrate ``head-
group'', which is attached to di-O-acyl-glycerol
derivatives via an ꢀ- or ꢁ-linkage. The simple lipids
with one to three sugar units in the ``headgroup''
and a glycerol part which is acylated with long
chain saturated or unsaturated aliphatic acids are
major structural components of cell membranes.
Other lipids, with more sugar units, are involved in
cell surface recognition events. Therefore, the pre-
paration and investigation of modi®ed structures
of this class of compounds is of interest.
2. Results and discussion
The concept for the synthesis of unsaturated
glycosyl glycerols has not yet been investigated.
First, the commercially available (R,S)-1,2-O-
isopropylidene glycerol was used as nucleophile to
test a Ferrier reaction with boron tri¯uoride ethe-
rate as catalyst. However, an excess of catalyst can
lead to opening of the acid labile isopropylidene
* Corresponding author. Fax: 4940 4123 4325; e-mail:
thiem@chemie.uni-hamburg.de
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00038-X

264
E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
ring and reduce the yield. Therefore, the reaction
was performed at low temperature in the presence
of only a catalytic amount of boron tri¯uoride
etherate. As expected, 3,4,6-tri-O-acetyl-1,5-anhy-
signal of H-4 was shifted to higher ®eld (4.95 ppm)
and the coupling constants J4,5ax, J4,5eq and J5ax,5eq
are in accord with a preferential 5Ho(D) con-
formation [10] and an axially oriented glycerol
aglycon.
dro-2-deoxy-d-arabino-hex-1-enitol
(3,4,6-tri-O-
acetyl-d-glucal, 1) reacted under typical Ferrier
conditions with 1.5 equivalents of 1,2-O-iso-
propylidene glycerol to give the ꢀ-glycoside 2 as a
mixtures of diastereomers, which was puri®ed after
¯ash chromatography in 85% yield (Scheme 1). No
ꢁ-anomer was detected and this result was con-
sistent with previous ®ndings [4±8].
It proved to be advantageous to select 1,3-di-O-
benzylglycerol [9] because the benzyl groups are
easy to remove by hydrogenation and showed sui-
table stability under acidic conditions. In a series of
experiments, this was reacted with various glycals
(Scheme 2).
Similar to monosaccharide glycals, the dis-
accharide glycals reacted smoothly with 1,3-di-O-
benzylglycerol under Ferrier conditions to give the
corresponding 2,3-dideoxy-hex-2-enopyranosides.
In both reactions of 1,3-di-O-benzylglycerol with
2,3,4,6-tetra-O-acetyl-ꢁ-d-galactopyranosyl- and
2,3,4,6-tetra-O-acetyl-ꢀ-d-glucopyranosyl-(1!4)-
3,6-di-O-acetyl-1,5-anhydro-2-deoxy-d-arabino-hex-
1-enitol (hexaacetyl lactal, 5 and hexaacetyl maltal,
6), exclusively the desired ꢀ-glycosides 11 and 12
were obtained in good yields.
Finally, methyl 3,4-di-O-acetyl-1,5-anhydro-2-
deoxy-d-arabino-hex-1-enitol-uronate (methyl-3,4-
di-O-acetyl-d-glucuronal, 7) [11] was treated cor-
respondingly to a€ord within 30 min the glycoside
13. By 1H NMR, this proved to be the ꢀ-anomer in
The ®rst attempt was with glucal 1 under boron
tri¯uoride etherate catalysis at
25 ꢀC. After
30 min at 10 ꢀC a new compound was detected by
TLC, which was isolated after work-up on silica gel
in 90% yield and characterised by NMR spectro-
scopy as the desired ꢀ-glycoside 8.
o
the energetically favoured H5(D) conformation as
con®rmed by coupling constants J1,2 and J4,5, with
values corresponding to literature data [12,13] for
components of similar structure.
By the corresponding reaction with tri-O-benzyl-
d-glucal (3) the desired ꢀ-glycoside 9a and benzyl
4,6-di-O-benzyl-2,3-dideoxy-ꢀ-d-erythro-hex-2-eno-
pyranoside (9b) were obtained in 66 and 18% yield,
respectively. All attempts to avoid the formation of
the undesired compounds 9b by variation of reac-
tion time, temperature and amount of catalyst were
unsuccessful, however, the compounds could be
separated easily by ¯ash chromatography.
The analogous reaction of 3,4-di-O-acetyl-1,5-
anhydro-2-deoxy-d-threo-pent-1-enitol (3,4-di-O-
acetyl-d-xylal, 4) with 1,3-di-O-benzylglycerol at
45 ꢀC a€orded a separable anomeric mixture 10a
and 10b in overall yield of 81%. Compound 10a
proved to be the ꢀ-anomer and compound 10b the
ꢁ-anomer, which could be established by 1H NMR
spectroscopy. In case of 10a, the chemical shift of
Compound 13 was deacetylated with sodium
carbonate in methanol to give 14 in almost quan-
titative yield. By reaction of this as aglycone with
the glucuronal 7 in the presence of stannic chloride
in dichloromethane at
45 ꢀC within 1 h, the
unsaturated disaccharide 15 was obtained in poor
yield (28%, Scheme 3). We did not succeed, how-
ever, in ®nding more suitable conditions to increase
the yield because always compound 13 formed as
by-product, apparently due to acetyl migration
1
(Scheme 3). In the H NMR spectrum of 15, the
large coupling between H-40 and H-50 of 9.7 Hz and
0
0
a small coupling constant of J1 ,2 (1.5 Hz) are in
accord with an ꢀ-anomer also in the non-reducing
ring.
Another proof for the supposed ꢀ con®guration
of glycoside 8 was obtained by hydrogenolysis with
Pd/C in methanol which simultaneously removed
the benzyl groups and the double bond to give the
H-4 (5.29 ppm) and the coupling constants J4,5ax
,
J4,5eq and J5ax,5eq indicate a favourable oH5(D)
conformation. In the 1H NMR spectrum of 10b the
Scheme 1.

E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
265
Scheme 2.
Scheme 3.
1
saturated glycoside 16. The H NMR spectrum of
16 showed an equatorial/axial and diequatorial
proton arrangement with typical small coupling
constants of J1,2ax=2.5 and J1,2eq&0 Hz.
Further deacetylation of 16 with sodium carbo-
nate gave the completely unprotected glycoside 17
in 91% yield. Alternatively, hydrogenolysis of all
benzyl groups and hydrogenation of the double

266
E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
bond in 9a directly led to the same compound 17 in
80% yield. The structure of 17 was established by
temperature, and as a single product, compound
18 could be isolated by ¯ash chromatography
(Scheme 4).
1
1H NMR and 13C DEPT spectroscopy. In the H
1
NMR spectrum, the J1,2ax and J1,2eq coupling con-
stants of approximately 1.0±2.5 Hz proved the
desired ꢀ-con®guration. In the 13C DEPT spectrum
signals of the CH2-groups, C-6 and C-10 or C-30 of
the glycerol residue were found at 62.15, 62.06, and
61.43 ppm, respectively.
Whereas in the H NMR spectrum of 18 the
signals of H-4 and H-1 from both unsaturated
rings coincide at 5.09 and 5.35 ppm, respectively,
the corresponding signals of H-2 and H-3 were
observed separatly. In comparison with compound
16, the signal of H-1 from the saturated ring was
shifted to lower ®eld (5.05 ppm). The coupling
constants between H-1 and H-2 of the unsaturated
It is known that structurally important gly-
coglycerol lipids are acylated at the glycerol moiety
with higher aliphatic acids. The synthesis of such
compounds, starting from glycosyl glycerol deriva-
tives with a free hydroxyl function at glycerol, was
already successfully achieved and reported [2,3].
However, a further functionalisation of these
hydroxy groups, for example, with carbohydrates
has not yet been described. It was an additional
purpose of these studies to synthesize such a tri-
glycosyl glycerol employing the Ferrier reaction.
Thus, compound 16 was treated with 2 equiva-
lents of glycal 1 in the presence of boron tri¯uoride
etherate to give the corresponding triglycosyl
glycerol 18 in acceptable 55% yield. At the begin-
ning of this reaction at 40 ꢀC the formation of
two products was detected by TLC. The polar
product disappeared however promptly at elevated
0
0
rings were identical (J1,2=J1 ,2 =1.5 Hz) and indi-
cate ꢀ-linkages in both cases. After hydrogenation
and deacetylation, the triglycosyl glycerol 18 could
be further functionalised, for example with higher
aliphatic acids to obtain sugar spacered glycerol
derivatives.
3. Experimental
General methods.ÐAll reactions were carried out
using dried solvents and were monitored by TLC
(E. Merck, Silica Gel plates GF245). The products
were puri®ed by ¯ash chromatography (E. Merck,
Silica Gel 60, 230±400 mesh) with distilled solvents.
Optical rotations were measured on a Perkin±Elmer
Scheme 4.

E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
267
243 polarimeter (sodium D line: 589 nm) in a 10 cm
polarimeter cuvette at 20 ꢀC. NMR spectra were
recorded on Bruker AMX-400 spectrometer
(400 MHz for 1H and 100.67 MHz for 13C) in
CDCl3 with TMS as internal standard.
General procedure for Ferrier reaction (GM 1).Ð
To a soln of glycal (1 equiv) and aglycon (1.1±1.5
equiv) in anhyd CH2Cl2 the catalyst (0.2 equiv)
was introduced in one portion at the given tem-
perature ( 20 to 45 ꢀC). The mixture was stirred
until the reaction was complete according to TLC.
Then, the reaction mixture was neutralized with
saturated NaHCO3 soln, washed with water, and
the organic phase was dried over MgSO4. After
®ltration, the solvent was evaporated under
reduced pressure and the crude product was pur-
i®ed on silica gel.
General procedure for deacetylation (GM 2).Ð
The compound was dissolved in dry MeOH and
one equivalent of Na2CO3 added. After complete
reaction (ca. 3 h) monitored by TLC, the mixture
was ®ltered and the solvent evaporated under
reduced pressure at 40 ꢀC. If required, the residue
was puri®ed by column chromatography on silica
gel. Water-soluble compounds were dissolved in
distilled water and then lyophilised.
General procedure for hydrogenation (GM 3).Ð
The compound was dissolved in dry MeOH and
10% Pd/C added. The mixture was hydrogenated
overnight under normal pressure. After complete
reaction, the catalyst was ®ltered over celite and
the soln was concentrated in vacuo.
66.56, 66.60, 64.85, 62.53 (C-6, C-10, C-30-glycerol),
(C-4, C-5), 26.39, 24.98 (2 isopropylidene-CH3),
20.50, 20.31 (2 OAc). Anal. Calcd for C16H24O8
(344.4): C, 55.81; H 7.02. Found: C, 55.23; H 7.09.
2-O-(4,6-Di-O-acetyl-2,3-dideoxy-a-d-erythro-
hex-2-enopyranosyl)-1,3-di-O-benzyl-glycerol (8).Ð
Triacetylglucal 1 (1.0 g, 3.67 mmol) and 1,3-di-O-
benzylglycerol (1.1 g, 4.04 mmol) were treated at
25 ꢀC in the presence of BF3±Et2O according to
GM 1. The reaction was stopped at 10 ꢀC and the
crude product was puri®ed by ¯ash chromato-
graphy (3:1 petroleum ether±EtOAc) to give 8
(1.61 g, 90%) as a syrup; [ꢀ]d +41.7ꢀ (c 0.6,
20
1
CHCl3); H NMR (CDCl3): ꢃ 7.35±7.26 (m, 10H,
H-Ph), 5.87 (ddꢁd, 1H, H-2), 5.83 (dt, 1H, H-3),
5.31 (dd, 1H, H-4), 5.28 (d, 1H, H-1), 4.56±4.53 (m,
4H, CH2-Ph), 4.17±4.09 (m, 2H, H-6a, H-6b), 4.01
(m, 1H, CH-glycerol), 3.62±3.50 (m, 5H, H-5, 2
CH2-glycerol), 2.08, 2.04 (each s, 3H, OAc); J1,2
1.2, J1,3 1.6, J2,3 10.8, J3,4 2.5, J4,5 9.6 Hz. Anal.
Calcd for C27H32O8 (484.6): C, 66.93; H 6.66.
Found: C, 66.84; H 6.52.
2-O-(4,6-Di-O-benzyl-2,3-dideoxy-a-d-erythro-
hex-2-enopyranosyl)-1,3-di-O-benzyl-glycerol (9a)
and Benzyl 4,6-Di-O-benzyl-2,3-dideoxy-a-d-ery-
thro-hex-2-enopyranoside (9b).ÐTribenzylglucal 3
(1.5 g, 3.6 mmol) and 1,3-di-O-benzylglycerol (1.5 g,
5.4 mmol) were treated at 35 ꢀC in the presence of
BF3±Et2O according to GM 1. The reaction was
stopped at
20 ꢀC and both products were
separated by ¯ash chromatography (8:1 petroleum
ether±EtOAc). Product 9a was isolated as a col-
ourless syrup in 65% (1.36 g) yield and product 9b
1-O-(4,6-Di-O-acetyl-2,3-dideoxy-a-d-erythro-
hex-2-enopyranosyl)-2,3-O-isopropylidene-glycerol
(2).ÐTriacetylglucal 1 (500 mg, 1.84 mmol) and
2,3-O-isopropylidenglycerol (340 ꢂl, 2.76 mmol)
were treated at 20 ꢀC in the presence of BF3±
Et2O according to GM 1. The reaction was stop-
ped after 1 h at 5 ꢀC and the crude product was
puri®ed by ¯ash chromatography (3:1 petroleum
ether-EtOAc) to give 2 (537 mg, 85%) as a colour-
20
as yellow syrup in 18% (270 mg) yield; 9a: [ꢀ]d
+19.7ꢀ (c 0.75, CHCl3); 1H NMR (CDCl3): ꢃ 7.38±
7.18 (m, 20H, H-Ph), 6.05 (ddꢁd, 1H, H-2), 5.78
(dt, 1H, H-3), 5.26 (dꢁbs, 1H, H-1), 4.71±4.40 (m,
8H, CH2-Ph), 4.19±4.11 (m, 2H, H-4, CH-gly-
cerol), 3.99 (ddd, 1H, H-5), 3.67 (dd, 1H, H-6a)
3.64±3.55 (m, 4H, 2 CH2-glycerol), 3.53 (dd, 1H,
H-6b); J1,2 2.0, J1,3 1.5, J2,3 10.2, J3,4 3.0, J4,5 9.7,
J5,6a 4.1, J5,6b 2.0, J6a,6b 10.2 Hz; 13C NMR
(CDCl3): ꢃ 138.32±126.63 (C-2, C-3, Ph-C), 94.56
(C-1), 75.57 (C-20-glycerol), 73.33, 73.25, 73.22,
70.93, 70.64, 70.39 (C-10, C-30-glycerol, 4 CH2 -Bn),
70.31, 69.06 (C-4, C-5), 68.72 (C-6). Anal. Calcd
for C37H40O6 (580.7): C, 76.53; H 6.94. Found: C,
less syrup; [ꢀ]d +88ꢀ (c 0.5, CHCl3); H NMR
(CDCl3): ꢃ (ddꢁd, 1H, H-2), 5.79 (dt, 1H, H-3),
5.24 (ddd, 1H, H-4), 5.00 (bs,1H, H-1), 4.23 (ddd,
1H, H-5), 4.15 (dd, 1H, H-6a), 4.11 (dd, 1H, H-6b),
4.04±3.48 (m, 5H, 2 CH2-glycerol, CH-glycerol),
2.04, 2.01 (each s, 3H, OAc), 1.36, 1.29 (each s,
each 3H, isopropylidene-CH3); J1,2 1.0, J1,3 1.5, J2,3
11.2, J2,4 1.5, J3,4 2.1, J4,5 9.7, J5,6a 5.6, J5,6b 2.6,
J6a,6b 12.2 Hz; 13C NMR (CDCl3) ꢃ 169.79, 167.53
(2 C=O), 128.89, 127.05 (C-2, C-3),109.65
(OCMe2), 94.09 (C-1), 74.13 (C-20-glycerol), 69.23,
20
1
76.49; H 6.98. 9b: [ꢀ]d +24.5ꢀ (c 0.5, CHCl3);
20
1H NMR (CDCl3): ꢃ 7.38±7.19 (m, 15H, H-Ph),
6.08 (ddꢁd, 1H, H-2), 5.79 (dt, 1H, H-3), 5.12
(dꢁbs, 1H, H-1), 4.83±4.43 (m, 8H, CH2-Ph), 4.19
(dd, 1H, H-4), 4.00 (ddd, 1H, H-5), 3.72 (dd, 1H,

268
E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
H-6a) 3.63 (dd, 1H, H-6b); J1,2 2.5, J1,3 2.0, J2,3
10.2, J3,4 2.0, J4,5 9.7, J5,6a 4.5, J5,6b 2.0, J6a,6b
10.7 Hz; 13C NMR (CDCl3): ꢃ 138.23±126.56 (C-2,
C-3, Ph-C), 93.99 (C-1), 73.41, 71.08, 70.06 (3 CH2 -
Bn), 70.42, 69.36 (C-4, C-5), 68.81 (C-6).
2-O-(4-O-Acetyl-2,3-dideoxy-a-d-glycero-pent-2-
enopyranosyl)-1,3-di-O-benzyl-glycerol (10a) and 2-
O-(4-O-acetyl-2,3-dideoxy-b-d-glycero-pent-2-eno-
pyranosyl)-1,3-di-O-benzylglycerol (10b).ÐDi-O-
acetyl-d-xylal 4 (400 mg, 2.0 mmol) and 1,3-di-O-
benzyl-glycerol (600 mg, 2.2 mmol) dissolved in
CH2Cl2 (20 mL) were treated in the presence of
BF3±Et2O at 45 ꢀC according to the GM 1. The
reaction was stopped at 5 ꢀC and the anomers
(ꢀ:ꢁ=1:5) were separated by ¯ash chromatography
(6:1 petroleum ether±EtOAc). Products 10a and
10b were isolated as a colourless syrups in 14%
(1.19 g, 86%) as a colourless syrup; [ꢀ]d +104.2ꢀ
20
(c 0.5, CHCl3); H NMR (CDCl3): ꢃ 7.28±7.15 (m,
1
10H, H-Ph), 6.03 (ddꢁd, 1H, H-2), 5.68 (dt, 1H,
H-3), 5.31 (dd, 1H, H-40), 5.17 (ddꢁd, 1H, H-1),
5.14 (dd, 1H, H-20), 4.93 (dd, 1H, H-30), 4.51±4.42
(m, 4H, 2 CH2-Ph), 4.46 (d, 1H, H-10), 4.13±3.94
(m, 7H, H-4, H-5, H-6a, H-6b, H-6a0, H-6b0, CH-
glycerol), 3.83 (ddd, 1H, H-50), 3.62±3.45 (m, 4H, 2
CH2-glycerol), 2.11, 2.01, 2.00, 1.98, 1.92 (each s,
3H, OAc); J1,2 2.0, J1,3 2.5, J2,3 10.2, J3,4 2.5, J10,20
0
0
0
0
0
0
0
0
0
0
8.1, J2 ,3 10.7, J3 ,4 3.6, J4 ,5 1.0, J5 ,6a 6.6, J5 ,6b
7.1 Hz; 13C NMR (CDCl3): ꢃ 170.30, 169.98,
169.79, 169.63, 168.93 (5 C=O), 137.97±126.60 (C-
2, C-3, C-aryl), 102.10 (C-10), 93.85 (C-1), 75.32 (C-
200-glycerol), 73.14, 70.48, 69.92, 68.42, 66.87, 66.45
(C-4, C-5, C-20, C-30, C-40, C-50), 72.93, 70.35,
70.29, 62.58, 60.81, 59.93 (C-6, C-60, C-100, C-300-
glycerol, 2 CH2-Ph), 20.61, 20.58, 20.36, 20.19,
20.09 (5 OAc). Anal.Calcd for C39H48O16 (772.8):
C, 60.61; H, 6.26. Found: C, 60.58; H, 6.24.
20
(115 mg) and 67% yield (555 mg); 10a: [ꢀ]d
+16.7ꢀ (c 0.3, CHCl3); 10b: [ꢀ]d +44.5ꢀ (c 0.6,
CHCl3); 10a: H NMR (CDCl3): ꢃ 7.38±7.23 (m,
20
1
10H, H-Ph), 5.91 (dd, 1H, H-2), 5.87 (dt, 1H, H-3),
5.29 (mc, 1H, H-4), 5.20 (bs, 1H, H-1), 4.54 (mꢁs,
4H, CH2-Ph), 4.10 (m, 1H, CH-glycerol), 3.81 (dd,
1H, H-5a), 3.77 (dd, 1H, H-5e), 3.70±3,54 (m, 4H,
2 CH2-glycerol), 2.04 (s, 3H, OAc); J1,2 1.0, J1,3
1.5, J2,3 10.2, J3,4 2.0, J4,5a 8.1, J4,5e 5.6, J5a,5e
11.2 Hz. 13C NMR (CDCl3): ꢃ 170.52 (C=O),
138.25±127.53 (C-2, C-3, Ph-C), 93.99 (C-1), 75.79
(C-20-glycerol), 73.39, 73.29, 70.83, 70.37 (C-10, C-
30-glycerol, 2 CH2-Bn) 65.15 (C-4), 59.64 (C-5),
21.01 (2 OAc). 10b: 1H NMR (CDCl3): ꢃ 7.38±7.25
(m, 10H, H-Ph), 6.10 (dd, 1H, H-2), 6.06 (dd, 1H,
H-3), 5.30 (d, 1H, H-1), 4.95 (m, 1H, H-4), 4.59-4.56
(m, 4H, CH2-Ph), 4.22 (dd, 1H, H-5a), 4.15 (m, 1H,
CH-glycerol), 3.78 (dd, 1H, H-5e), 3.70-5.53 (m, 4H,
2 CH2-glycerol), 2.11 (s, 3H, OAc); J1,2 1.5, J2,3 10.2,
J3,4 3.5, J4,5a 3.1, J4,5e 1.0, J5a,5e 13.2 Hz; 13C NMR
(CDCl3): ꢃ 170.67 (C=O), 138.22±124.84 (C-2, C-3,
Ph-C), 92.87 (C-1), 75.37 (C-20-glycerol), 73.29,
71.33, 70.75, 69.65 (C-10, C-30-glycerol, 2 CH2 -Bn)
63.45 (C-4), 61.21 (C-5), 21.15 (2 OAc). Anal.Calcd
for C24H28O6 (412.5): C, 69.89; H, 6.84. Found: 10a:
C, 69.76; H, 6.77; 10b: C, 69.79; H, 6.78.
1,3-Di-O-benzyl-2-O-[4-O-(2,3,4,6-tetra-O-ace-
tyl-a-d-glucopyranosyl)-6-O-acetyl-2,3-dideoxy-a-
d-erythro-hex-2-enopyranosyl]-glycerol (12).ÐIn
analogy to the preparation of 11, hexaacetylmaltal
6 (1.0 g, 1.78 mmol) and 1,3-di-O-benzylglycerol
(0.73 g, 2.67 mmol) were converted into 12 (1.03 g,
75%); colourless syrup; [ꢀ]d20 +93ꢀ (c 1.5, CHCl3);
1H NMR (CDCl3): ꢃ 7.38±7.14 (m, 10H, H-Ph),
5.75 (s, 2H, H-2, H-3), 5.36 (t, 1H, H-40), 5.23 (d,
1H, H-10), 5.17 (bs, 1H, H-1), 5.01 (dd, 1H, H-30),
4.77 (dd, H-20), 4.47 (d, 4H, 2 CH2-Ph), 4.19 (dd,
1H, H-6a0), 4.16 (d, 1H, H-4), 4.10±3.99 (m, 4H, H-
5, H-6a, H-6b, CH-glycerol), 3.97 (dd, 1H, H-6b0),
3.92 (ddd, 1H, H-50), 3.62±3.47 (m, 4H, 2 CH2-
glycerol), 2.03, 2.01, 2.00, 1.98, 1.95 (each s, 3H,
0
0
0
0
0
0
0
0
OAc); J4,5 9.7, J1 ,2 4.1, J2 ,3 10.2, J3 ,4 9.7, J4 ,5
10.2, J5 ,6a 3.6, J5 ,6b 2.5, J6a ,6b 12.2 Hz; 13C NMR
(CDCl3): ꢃ=170.19, 170.17, 169.79, 169.54, 169.11
(5 C=O), 137.84±127.05 (C-2, C-3, C-aryl), 93.71,
93.47 (C-1, C-10), 75.33 (C-200-glycerol), 73.01,
72.94, 69.84, 69.38, 62.75, 61.45 (C-6, C-60, C-100,
C-300-glycerol, 2 CH2-Ph), 70.33, 69.17, 68.91,
68.43, 67.74, 66.69 (C-4, C-5, C-20, C-30, C-40, C-
50), 20.59, 20.48, 20.33, 20.22, 20.16 (5 OAc). Ana-
l.Calcd for C39H48O16 (772.8): C, 60.61; H, 6.26.
Found: C, 59.97; H, 6.38.
0
0
0
0
0
0
1,3-Di-O-benzyl-2-O-[4-O-(2,3,4,6-tetra-O-ace-
tyl-b-d-galactopyranosyl)-6-O-acetyl-2,3-dideoxy-
a-d-erythro-hex-2-enopyranosyl]-glycerol (11).Ð
Hexaacetyllactal 5 (1.0 g, 1.78 mmol) and 1,3-di-O-
benzylglycerol (0.73 g, 2.67 mmol) were treated at
20 ꢀC in the presence of BF3±Et2O according to
GM 1. The reaction was stopped at 10 ꢀC and the
crude product was puri®ed by ¯ash chromato-
graphy (2:1 petroleum ether±EtOAc) to give 11
1-O-(1,3-Di-O-benzyl-glyceryl)-4-O-acetyl-2,3-
dideoxy-a-d-erythro-hex-2-enopyranuronic acid
methylester (13).ÐMethyl 3,4-diacetyl-d-glucur-
onal 7 (100 mg, 0.77 mmol) and 1,3-di-O-benzyl-
glycerol (225 mg, 0.94 mmol) were treated at
40 ꢀC in the presence of BF3±Et2O according to

E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
269
GM 1. The reaction was stopped at 20 ꢀC and the
crude product was puri®ed by ¯ash chromato-
graphy (3:1 toluene±EtOAc) to give 13 (229 mg,
80%) as a colourless syrup; [ꢀ]d +56.8ꢀ (c 0.25,
(each s, 3H, 2 OMe), 3.60±3.50 (m, 4H, 2 CH2-gly-
cerol), 2.05 (s, 3H, OAc); J1,2 1.5, J1,3 1.5, J2,3 10.2,
J3,4 2.0, J4,5 8.7, J1 ,2 .5, J3 ,4 1.5, J4 ,5 9.7 Hz; 13C
NMR (CDCl3): ꢃ 171.47, 170.57, 169.16 (3 C=O),
137.97±126.52 (C-2, C-3, C-20, C-30, Ph-C), 110.61
(C-10), 93.66 (C-1), 76.51 (C-200-glycerol), 73.47,
73.39, 71.31, 71.26 (C-100, C-300-glycerol, 2 CH2-
Bn), 72.36, 69.63, 68.40, 65.64 (C-4, C-5, C-40, C-
50), 52.69, 52.60 (2 OMe), 20.83 (OAc).
0
0
0
0
0
0
1
CHCl3); H NMR (CDCl3): ꢃ 7.39±7.25 (m, 10H,
H-Ph), 5.88 (dd, 1H, H-3), 5.84 (ddꢁd, 1H, H-2),
5.56 (dd, 1H, H-4), 5.37 (bs, 1H, H-1), 4.54 (d, 1H,
H-5), 4.52 (s, 4H, CH2-Ph), 4.16 (m, 1H, CH-gly-
cerol), 3.67 (s, 3H, OMe), 3.66±3.50 (m, 4H, 2
CH2-glycerol), 2.08 (s, 3H, OAc); J1,2 1.5, J1,3 1.5,
J2,3 10.2, J3,4 2.5, J4,5 9.7 Hz; 13C NMR (CDCl3): ꢃ
170.24, 169.55 (2 C=O), 138.29±127.59 (C-2, C-3,
Ph-C), 94.28 (C-1), 76.17 (C-20-glycerol), 73.47,
73.34, 70.54, 70.23 (C-10, C-30-glycerol, 2 CH2 -Bn),
68.19, 66.02 (C-4, C-5), 52.59 (OMe), 20.97 (OAc).
Anal.Calcd for C26H30O8 (470.5): C, 66.37; H,
6.43. Found: C, 66.35; H, 6.40.
2-O-(4,6-Di-O-acetyl-2,3-dideoxy-a-d-erythro-
hexopyranosyl)-glycerol (16).ÐCompound 8 (1.0 g,
2.06 mmol) was hydrogenated according to GM 3.
After puri®cation by ¯ash chromatography (3:1
EtOAc±petroleum ether), the colourless syrup 16
(505 mg, 80%) was obtained; [ꢀ]d +10ꢀ (c 0.,
20
1
CHCl3); H NMR (CDCl3): ꢃ 4.98 (bs, 1H, H-1),
4.65 (m, 1H, H-4), 4.14±4.03 (m, 3H, H-6a, H-6b,
CH-glycerol), 3.74±3.56 (m, 5H, H-5, 2 CH2-gly-
cerol), 2.04, 2.01 (each s, 3H, OAc), 2.00±1.74 (m,
4H, H-2a, H-2e, H-3a, H-3e); J1,2a 2.5, J5,6a 5.1,
J5,6b 2.5, J6a,6b 12.2 Hz; 13C NMR (CDCl3): ꢃ
170.40, 169.55 (2 C=O), 96.21 (C-1), 80.37 (C-20-
glycerol), 69.13, 67.52 (C-4, C-5), 63.09, 62.97, 61.94
(C-6, C-10, C-30-glycerol), 28.51, 23.33, (C-2, C-3),
20.57, 20.24 (2 OAc). Anal. Calcd for C13H22O8
(306.3): C, 50.98; H 7.24. Found: C, 50.58; H 7.09.
2-O-(2,3-Dideoxy-a-d-erythro-hexopyranosyl)-
glycerol (17).ÐMethod A: Compound 16 (260 mg,
0.63 mmol) was deacetylated according to GM 2.
After puri®cation of the crude product on silica gel
(6:1 CH2Cl2-MeOH), 17 (172 mg, 91%) was
obtained as a yellow syrup; method B: compound 9a
(300 mg, 0.52 mmol) was hydrogenated according to
GM 3 to give 17 (92 mg, 80%); [ꢀ]d20 +80.7ꢀ (c 0.3,
1-O-(1,3-Di-O-benzyl-glyceryl)-2,3-dideoxy-a-d-
erythro-hex-2-enopyranuronic acid methylester
(14).ÐCompound 13 (200 mg, 0.43 mmol) was
deprotected according to GM 2 to yield after
chromatographic puri®cation (3:1 toluene±EtOAc)
the colourless syrup 14 (170 mg, 93%); [ꢀ]d +2ꢀ
20
1
(c 0.25, CHCl3); H NMR (CDCl3): ꢃ 7.39±7.23
(m, 10H, H-Ph), 5.95 (ddꢁd, 1H, H-2), 5.79 (dt,
1H, H-3), 5.33 (d, 1H, H-1), 4.55 (s, 2H, CH2-Ph),
4.53 (d, 1H, H-5), 4.36 (s, 2H, CH2-Ph), 4.18 (m,
1H, CH-glycerol), 3.72 (s, 3H, OMe), 3.69±3.47 (m,
5H, H-4, 2 CH2-glycerol), 2.90 (d, 1H, 4-OH); J1,2
1.5, J1,3 2.0, J2,3 10.2, J3,4 1.5, J4,OH 3.1, J4,5 8.2 Hz;
13C NMR (CDCl3): ꢃ 169.52 (C=O), 138.33±
126.33 (C-2, C-3, Ph-C), 94.58 (C-1), 76.17 (C-20-
glycerol), 73.46, 73.36, 70.68, 70.49 (C-10, C-30-gly-
cerol, 2 CH2-Bn), 65.28, 57.62 (C-4, C-5), 52.59
(OMe). Anal.Calcd for C24H28O7 (428.5): C, 67.28;
H, 6.59. Found: C, 67.38; H, 6.56.
1
CHCl3); H NMR (MeOD): ꢃ 5.16 (ddꢁd, 1H, H-
1), 3.99±3.56 (m, 9H, H-4, H-5, H-6a, H-6b, CH-
glycerol, 2 CH2-glycerol), 2.07±1.39 (m, 4H, H-2ae,
H-3ae); J1,2a 2.5, J1,2e 1.0 Hz; 13C NMR (MeOD): ꢃ
96.08 (C-1), 78.57 (C-20-glycerol), 74.52, 66.24 (C-4,
C-5), 62.15, 62.06, 61.43 (C-6, C-10, C-30-glycerol),
29.45, 27.06 (C-2, C-3). Anal.Calcd for C9H18O6
(222.2): C, 48.64; H, 8.16. Found: C, 48.06; H, 8.24.
1,3-Di-O-(4,6-di-O-acetyl-2,3-dideoxy-a-d-ery-
thro-hex-2-enopyranosyl)-2-O-(4,6-di-O-acetyl-2,3-
dideoxy-a-d-erythro-hexopyranosyl)-glycerol (18).Ð
Triacetylglucal 1 (90 mg, 0.33 mmol) and com-
pound 16 (50 mg, 0.16 mmol) were treated at
45 ꢀC under BF3±etherate catalysis according to
GM 1. The reaction was stopped after 1 h at
20 ꢀC and the major product was isolated by
column chromatography on silica gel (2:1 petro-
leum ether±EtOAc) to a€ord 17 (65 mg, 55%) as a
1-O-(1,3-Di-O-benzyl-glyceryl)-4-O-(methyl-4-O-
acetyl-2,3-dideoxy-a-d-erythro-hex-2-enopyranosyl-
uronate)-2,3-dideoxy-a-d-erythro-hex-2-enopyran-
uronic acid methylester (15).ÐCompounds 7 (40 mg,
0.15 mmol) and 14 (77 mg, 0.18 mmol) were treated
at 45 ꢀC in the presence of a catalytic amount of
SnBr4 according to GM 1. The reaction was stopped
after 1 h at 25 ꢀC and the crude product was pur-
i®ed by ¯ash chromatography (5:1 toluene±EtOAc)
to give 15 (27 mg, 28%) as a syrup; [ꢀ]d20 +25.2ꢀ (c
1
0.3, CHCl3); H NMR (CDCl3): ꢃ 7.39±7.23 (m,
10H, H-Ph), 6.38 (s, 2H, H-20, H-30), 5.92 (ddꢁd,
1H, H-2), 5.86 (dt, 1H, H-3), 5.57 (dd, 1H, H-40),
5.29 (bs, 1H, H-1), 5.24 (bs, 1H, H-1), 4.60 (d, 1H,
H-5), 4.58±4.50 (m, 5H, H-50, 2 CH2-Ph), 4.03 (m,
1H, CH-glycerol), 3.81 (ddꢁd, 1H, H-4), 3.77, 3.76

270
E. Wieczorek, J. Thiem/Carbohydrate Research 307 (1998) 263±270
colourless syrup; [ꢀ]d +154ꢀ (c 0.25, CHCl3); H
NMR (CDCl3): ꢃ 5.92 (ddꢁd, 1H, H-2), 5.91
(ddꢁd, 1H, H-20), 5.84 (dt, 1H, H-3), 5.81 (dt, 1H,
H-30), 5.35 (m, 2H, H-4, H-40), 5.09 (bs, 2H, H-1,
H-10), 5.05 (d, 1H, H-100), 4.77 (m, 1H, H-400), 4.33±
4.03 (m, 10H, CH-glycerol, H-5, H-50, H-500, H-6a,
H-6b, H-6a0, H-6b0, H-6a00, H-6b00), 3.97±3.90 (m,
2H, 2 CH2-glycerol), 3.70±3.58 (m, 2H, 2 CH2-gly-
cerol), 2.11±2.05 (6s, 18H, 6 OAc), 2.04±1.82 (m,
4H, H-2ae00, H-3ae00); J1,2 1.5, J1,3 2.0, J2,3 10.2, J3,4
References
20
1
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0
0
0
0
0
0
0
0
00
00
2.5, J1 ,2 1.5, J1 ,3 2.0, J2 ,3 10.2, J3 ,4 2.5, J1 ,2a
2.0 Hz; 13C NMR (CDCl3) : ꢃ= 170.24±169.43 (6
C=O), 128.95, 128.94, 126.95, 126.93 (C-2, C-3, C-
20, C-30), 95.27, 94.31, 94.28 (C-1, C-10, C-100), 73.74
(C-2*-glycerol), 68.34, 68.33 (C-1*, C-3*-glycerol),
67.80, 67.21, 66.84, 66.59, 66.58, 64.78 (C-4, C-5,
C-40, C-50, C-400, C-500), 62.60, 62.45, 62.38 (C-6, C-
60, C-600), 28.45, 23.37, (C-200, C-300), 20.60±20.34 (6
OAc). Anal.Calcd for C33H46O18 (730.7): C, 54.24;
H, 6.35. Found: C, 53.72; H, 6.35.
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Support of this work by the Fonds der Che-
mischen Industrie and the Deutsche For-
schungsgemeinschaft is gratefully acknowledged.