Glycosylation employing glycopyranosyl fluorides promoted by TiF4 under mild conditions

Article abstract of DOI:10.1080/07328303.2020.1837151

Glycopyranosyl fluorides are shown as efficient glycosyl donors by glycosylation of appropriate aglycon structures under mild conditions with Lewis acid catalysis in anhydrous ether or acetonitrile. Further direct reaction sequences gave naturally occurri

Full text of DOI:10.1080/07328303.2020.1837151

Journal of Carbohydrate Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lcar20
Glycosylation employing glycopyranosyl fluorides
promoted by TiF under mild conditions
4
Joachim Thiem & Matthias Wiesner
To cite this article: Joachim Thiem & Matthias Wiesner (2020): Glycosylation employing
glycopyranosyl fluorides promoted by TiF under mild conditions, Journal of Carbohydrate
4
Chemistry, DOI: 10.1080/07328303.2020.1837151
To link to this article: https://doi.org/10.1080/07328303.2020.1837151
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JOURNAL OF CARBOHYDRATE CHEMISTRY
https://doi.org/10.1080/07328303.2020.1837151
Glycosylation employing glycopyranosyl fluorides
promoted by TiF under mild conditions
4
Joachim Thiem and Matthias Wiesner
Department of Chemistry, Faculty of Science, University of Hamburg, Hamburg, Germany
ABSTRACT
ARTICLE HISTORY
Glycopyranosyl fluorides are shown as efficient glycosyl donors
by glycosylation of appropriate aglycon structures under mild
conditions with Lewis acid catalysis in anhydrous ether or
acetonitrile. Further direct reaction sequences gave naturally
occurring disaccharide derivatives of biological interest.
Received 2 September 2020
Accepted 11 October 2020
KEYWORDS
Glycopyranosyl fluorides;
titanium tetrafluoride;
boron trifluoride etherate;
glycosylation; 1-4- and 1-3-
linked-disaccharides
GRAPHICAL ABSTRACT
Introduction
The use of glycosyl fluorides as donor structures for glycosylation was pre-
viously considered inappropriate due to their reduced reactivity under sil-
ver salt catalysis. In basic media such as sodium methylate in methanol or
barium hydroxide in water, unprotected glycosyl fluorides led to formation
[
1]
of methyl glycosides or anhydrides via epoxide-type intermediates. With
a-D-mannopyranosyl fluoride di- and oligosaccharides could be isolated,
[
2]
presumably formed again via epoxide intermediates. Also, the reaction of
2
,3,4,6-tetra-O-acetyl–a-D-glucopyranosyl fluoride with various reagents
[
3]
gave a mixture of products, among which trehalose could be isolated.
Phenyl b-D-glucopyranoside could be obtained from b-D-glucopyranosyl
[
4]
fluoride and barium phenolate in water.
None of these reports qualified for synthetic requirements, until
Mukaiyama et al. took up the employment of glycosyl fluorides for
CONTACT Joachim Thiem
thiem@chemie.uni-hamburg.de
Department of Chemistry, Faculty of Science,
University of Hamburg, Martin-Luther-King-Platz 6, Hamburg, D-20146, Germany
ß 2020 Taylor & Francis Group, LLC

2
J. THIEM AND M. WIESNER
[
5]
synthesis. Indeed, more sophisticated glycosides could be prepared using
SnCl /AgClO leading with notable stereoselectivity to 1,2-cis glycosides.
2
4
Further,
reported.
a
considerable number of tin(II)-catalyst systems were
Extensive studies of Noyori et al. employing perbenzylated
[
6–10]
glycosyl fluorides under catalysis of SiF and Me SiF with alcohols showed
4
3
preferred formations in high yields of a-glycosides in ether and b-glyco-
[
11]
sides in acetonitrile.
Much easier was the use of BF -Et O as demon-
3 2
[
12–15]
strated in several synthetic studies.
Apparently, for glycosylations
with perbenzylated as well as peracetylated glycosyl fluorides metal fluo-
rides of the fourth and fifth group of the periodic table represented the
[
16]
most advantageous Lewis acids.
Thus, SnF and TiF proved to be
4 4
effective heterogeneous catalysts in anhydrous polar (acetonitrile) or less
[
16,17]
polar (ether) solvents with convenient workup procedures.
Several
surveys on the synthetic use of glycosyl fluorides were provided
[
18–21,22]
recently.
In general, for unprotected as well as peracetylated or perbenzylated
glycosyl fluorides (e.g. Glc or Gal) the b-anomers proved to be less sta-
ble than the robust a-anomers. Since we were interested in using glyco-
syl fluorides as donor structures preferentially for synthetic purposes,
several selectively prepared carbohydrate aglyconic molecules for forma-
tion of biologically relevant disaccharide derivatives were checked.
Results and discussion
Synthesis of 2-acetamido-2-deoxy-4-O-(a-D-galactopyranosyl)-D-
glucopyranose (a-Gal-1 2 4-GlcNAc)
One of the important disaccharide derivatives of blood group antigens is
N-acetyl-isolactosamine (a-Gal-1 ꢀ 4-GlcNAc), which was previously syn-
[
23,24]
thesized employing the orthoester method by Sinay et al.
Employing
glycosyl fluorides, our attempt started with the perbenzylated galactopyra-
[
25]
[26]
nosyl fluoride (1)
and the 2-acetamido-1,6-anhydro gluco derivative 2
as aglycon in anhydrous acetonitrile and with TiF catalysis (Sch. 1). The
4
disaccharide was formed in a yield of 79% with both the a-anomer (3) and
b-anomer (4) in a favorite ratio of 83:17; however, since no chromato-
graphic separation could be realized we had to change the approach.
Therefore, glycosyl fluoride 1 and 1,6:2,3-dianhydro-b-D-mannopyranose
[27]
(5)
as aglycon structure and precursor were selected, which gave under
similar conditions the a- and b-1-4-linked disaccharides (6) and (7) in 86%
yield and a ratio of 74:26, which could be readily separated by chromatog-
raphy. The a-component 6 was hydrogenolized to give compound 8, in which
opening of the 2,3-anhydro ring with sodium azide led to the 2-azido-gluco
derivative 9. Direct peracetylation gave the crystalline derivative 10; however,

JOURNAL OF CARBOHYDRATE CHEMISTRY
3
Scheme 1. Synthesis of 2-acetamido-2-deoxy-4-O-(a-D-galactopyranosyl)-D-glucopyranose (a-Gal-
-4-GlcNAc). Reaction conditions: (a) TiF /CH CN; (b) Pd-C/H /CH OH; (c) NaN /EtOH/H O; (d)
1
4
3
2
3
3
2
Ac O/py; (e) Pd-C/H /HOAc; (f) Ac O/BF ; (g) NaOMe/MeOH.
2
2
2
3
the yield of 28% was not convincing at all. Hydrogenation of the azide in 10
worked as expected and acetylation led to the crystalline compound 12.
[
26]
An explicitly preferred method
was heating epoxide 8 with aqueous
ammonia under pressure, which after subsequent peracetylation gave the
crystalline material 12 in 80% yield. Further, the 1,6-anhydro ring was
opened with BF -Et O/acetic anhydride, which gave the crystalline com-
3
2
pound 13 in 63% yield. Finally, O-deacetylation under Zempl ꢀe n condi-
[
28]
tions
provided the target compound 2-acetamido-2-deoxy-4-O-(a-D-

4
J. THIEM AND M. WIESNER
galactopyranosyl)-D-glucopyranose (N-acetyl-isolactosamine, Gal-a,1 ꢀ 4-
GlcNAc, 14) (Sch. 1).
Synthesis of 2-acetamido-3-O-(b-D-glucopyranosyluronate)-2-deoxy-D-
glucopyranose (hyalobiuronic acid, b-GlcUA-1-3-GlcNAc)
The dominant compound in connective tissues such as umbilical cord or
vitreous body of the eye is the polysaccharide hyaluronic acid, and by
[
29,30]
acid hydrolysis
acid.
it gave a disaccharide identified as hyalobiuronic
Previous syntheses of some derivatives of this repeating unit of
the polysaccharide was reported by Koenigs-Knorr type condensation
[
31]
[
32]
catalyzed by mercury cyanide.
Since acetylated b-glycosyl fluorides
were reported to react stereospecifically via an acetoxonium intermediate
[
33]
to give 1,2-trans products, the glucopyranosyluronate fluoride 15
was
the ideal donor structure to react with the 1,6-anhydro-gluco derivative
[
33]
16.
By reaction with TiF in anhydrous acetonitrile the yield of the
4
b,1-3-linked disaccharide 17 was 55%; however, with BF in dichlorome-
3
thane the yield could be improved to 67%. Simultaneous de-benzylation
and reduction of the azido group by hydrogenation in acetic acid at
Scheme 2. Synthesis of hyalobiuronic acid methyl ester. Reaction conditions: (a) BF -Et O; (b)
3
2
Pd-C/H /HOAc; (c) Ac O, pyr; (d) BF -Et O/HOAc.
2
2
3
2

JOURNAL OF CARBOHYDRATE CHEMISTRY
5
Table 1. Glycosylation reactions of various acceptors with glycoyl fluorides.
Glycosyl Fluoride
Aglycon
22
Disaccharides
23 + 24
Yield (%)
a,1-4 : b,1-4
2
1
85
81
55
65
62
:
45
35
38
1
22
25 + 26
:
1
28
29 + 30
85
:
ꢁ
2
; anhydr. Et O, 3h, 0 C
TiF
4
ꢁ
4
0 C gave the intermediate 18, which was peracetylated to result in for-
mation of the crystalline compound 19 in 68% yield. Finally, the 1,6-
anhydro ring was cleaved with BF -Et O/Ac O at room temperature to
3
2
2
give the crystalline peracetate 20 in 75% yield. Deacetylation under
[
28]
Zempl ꢀe n conditions
could not be realized due to extensive degrada-
tions. This compound is extremely base labile presumably because of the
b-elimination tendency known for uronic acid derivatives (Sch. 2).
Synthesis of various a-1-4-linked disaccharides
Whereas bacterial infection of animal cells are common to start with attach-
ment of mannose-rich oligo- and polysaccharides, properties of disaccharide
derivatives with gluco and galacto units are unknown concerning potential
inhibitory activities. Therefore, syntheses of predominantly a-1-4-linked disac-
charides with Glc-Gal, Gal-Gal, and Gal-Glc arrangement were of interest. As
[
34]
donor structures perbenzylated a-D-glycopyranosyl fluorides of gluco-(21)
[25]
and galacto-(1)
the unblocked fluorides.
selectively unblocked tetra-O-benzyl derivatives of galacto-(22)
configurations were easily obtained by perbenzylation of
[25]
Their treatment under TiF catalysis with the C4-
and gluco-
configurations in anhydrous ether at 0 C for 3 h gave the disaccharide
4
[24]
[26]
ꢁ
(28)
derivatives in over 80% yield and an a:b ratio of about 60:40 (Table 1). Their
separation by chromatography was feasible, however, reduced the overall yield
considerably. In In case of disaccharide 25 hydrogenolysis in methanol led to
the
naturally
occurring
4-O-(a-D-galactopyranosyl)-D-galactopyranose
[35–38]
(27)
as amorphous material (Sch. 3).
Conclusion
This contribution reports on effective formations of disaccharide fragments
by glycosylations employing glycopyranosyl fluorides under Lewis acid
catalysis in anhydrous ether or acetonitrile. Further, straightforward reac-
tion sequences leading to the naturally occurring disaccharide derivatives
are described.

6
J. THIEM AND M. WIESNER
Scheme 3. Synthesis of various a-1-4-linked disaccharides. Reaction conditions: (a) TiF /Et O;
4
2
(
b) Pd-C/H /CH OH.
2 3
Experimental
General methods
All reactions were monitored by thin layer chromatography on silica gel
foils GF254 (Merck). Detection was by UV or spraying with 20% ethanolic
sulfuric acid and subsequent heating. Column chromatography was done
on silica gel 60 (230-400 mesh, Merck) by the flash mode with the solvent
1
mixture recorded. H NMR (300 MHz) spectra were done on Bruker WM-
300. Melting points are uncorrected and were taken with a Reichert heating
table microscope. Optical rotations were measured with Perkin-Elmer
ꢁ
polarimeter 241, cuvette length 10 cm, and temperature 20 C. Solvents and
reagents including TiF were purchased from Sigma-Aldrich.
4
Acetylation (general procedure, GP1)
The starting material dissolved in anhydrous pyridine was treated with
ꢁ
acetic anhydride (3 eq) for 1–3 h at 20 C. The mixture was mixed with ice
water and extracted with dichloromethane. The organic phase was washed
with saturated sodium hydrogen carbonate and water, dried over MgSO4,
filtered, co-evaporated with toluene and purified by chromatography.

JOURNAL OF CARBOHYDRATE CHEMISTRY
7
Glycosylation with TiF (general procedure, GP2)
4
Glycosyl fluoride (1 mmol) and aglycon (1 mmol) dissolved in anhydrous
solvent (3–5 mL) were stirred with activated molecular sieves 3 A (50 mg,
ꢁ
dried for 24 h at 300 C in high vacuo). TiF (0.1–5.0 eq.) was added and
4
ꢁ
stirring continued at 20 C for the given time. For work up the mixture
was filtered over silica gel, then poured into ice cold, aqueous saturated
sodium hydrogen carbonate, extracted with ethyl acetate or dichlorome-
thane, dried (MgSO ) and evaporated to give the raw material to be puri-
4
fied further.
2
-Acetamido-3-O-acetyl-4-O-(2,3,4,6-tetra-O-benzyl-a-D-galactopyranosyl)-1,6-
anhydro-2-deoxy-b-D-glucopyranose (3)
[
25]
2
0
7
,3,4,6-Tetra-O-benzyl-a-D-galactopyranosyl
fluoride
(1,
170 mg,
[
26]
.31 mmol) and 2-acetamido-1,6-anhydro-2-deoxy-b-D-glucopyranose (2
7 mg, 0.31 mmol) dissolved in anhydrous acetonitrile (5 mL) were treated
with titanium tetrafluoride (40 mg, 0.32 mmol) for 2 h at 0 C and worked
up according to GP2. The raw material (187 mg, 78%) contained a mixture
,
ꢁ
1
of anomers a(3): b(4) ¼ 83: 17 according to H NMR. By chromatography
in various solvent mixtures only the a-anomer 3 could be obtained pure as
ꢁ
20
1
amorphous material; mp 125–127 C, [a]D ¼ þ 37.7 (c ¼ 1.8, CHCl ); H
3
NMR (300 MHz, C D ): d ¼ 6.99–7.38 (m, 20H, Aryl-H), 5.79 (s, 1H, H-1),
6
6
4.43 (d, 1H, J
¼ 8.4 Hz, H-2), 4.95 (m, 1H, H-3), 3.42 (m, H-4), 4.25
2
,NH
0
(
(
5
mc, 2H, H-5, ꢀ5 ), 3.52 (dd, 1H, J
¼ 0.7, J
¼ 7.7 Hz, H-6a), 3.39
5
,6a
6a,6b
dd, 1H, J5 ¼ 5.7, J
¼ 7.7 Hz, H-6b), 6.65 (d, 1H,J
¼ 8.4 Hz, NH),
0
,6b
6a,6b
2,NH
0
.42 (d, 1H, J
0
¼ 3.5 Hz, H-1 ), 4.22 (dd, 1H, J
0
¼ 3.5, J
¼ 10.1 Hz,
0
1ꢀ, 2
1ꢀ, 2
2ꢀ, 3
0
0
H-2 ), 3.96 (dd, 1H, J
0
¼ 10.1, J
0
¼ 2.9 Hz, H-3 ), 3.91 (dd, 1H, J
¼
2
ꢀ, 3
0
3ꢀ, 4
3ꢀ, 4
2
3
4
.9, J 4ꢀ, 5
0
¼ 1.1 Hz, H-4 ), 3.77 (dd, 1H, J
¼ 6.3, J
¼ 9.4 Hz, H-6 ꢀa ),
5ꢀ, 6 ꢀa
6 ꢀa ,6bꢀ
.70 (dd, 1H, J
¼ 6.5, J
¼ 9.4 Hz, H-6bꢀ), 4.30, 4.36, 4.47(2), 4.52,
5ꢀ, 6bꢀ
6 ꢀa ,6bꢀ
.56(2), 5.02 (4 AB, 8H, 4 x OCH Aryl), 1.47, 1.49 (2 s, each 3H, OAc,
2
NAc). Calcd. for C H NO (767.87): C, 68.82; H, 6.43; N, 1.82. Found:
4
4
49
11
C, 68.80; H, 6.58; N, 1.21.
1
,6:2,3-Dianhydro-4-O-(2,3,4,6-tetra-O-benzyl-a-D-galactopyranosyl)-b-D-
mannopyranose (6) and 1,6:2,3-Dianhydro-4-O-(2,3,4,6-tetra-O-benzyl-b-D-
galactopyranosyl)-b-D-mannopyranose (7)
[
25]
2
,3,4,6-Tetra-O-benzyl-a-D-galactopyranosyl fluoride (1,
1.1 g, 2.3 mmol)
[
27]
and 1,6:2,3-dianhydro-b-D-mannopyranose (5 , 292 mg, 2.03 mmol) dis-
solved in anhydrous acetonitrile (20 mL) were treated with titanium tetra-
ꢁ
fluoride (251 mg, 2.03 mmol) for 2 h at 0 C and worked up according to
GP2. The raw material (1.14 g, 86%) contained a mixture of anomers a(6):

8
J. THIEM AND M. WIESNER
1
b(7) ¼ 74: 26 according to H NMR. Separation of the anomers was by
chromatography (dichloromethane/ethyl ether 20: 1).
2
0
1
Compound 6: colorless sirup, [a]D ¼ þ 32.1 (c ¼ 1.1, CHCl ); H NMR
3
(
3
3
2
(
4
2
300 MHz, C D ): d ¼ 7.05–7.40 (m, 20H, Aryl-H), 5.40 (d, 1H, J
¼
¼
¼
6
6
1,2
.1 Hz, H-1), 2.80 (dd, 1H, J ¼ 3.1, J ¼ 3.8 Hz, H-2), 3.06 (d, 1H, J
1,2
2,3
2,3
.8, J3,4 ¼ 0 Hz, H-3), 3.42 (s, 1H, J3,4 ¼ J ¼ 0 Hz, H-4), 4.75 (dd, 1H, J
4,5
5,6a
.0, J5,6b ¼ 6.9 Hz, H-5), 3.47 (dd, 1H, J ¼ 2.0, J
¼ 7.3 Hz, H-6a), 3.35
5,6a
6a,6b
0
dd, 1H, J5 ¼ 6.9, J
¼ 7.3 Hz, H-6b), 4.99 (d, 1H, J
0
¼ 3.7 Hz, H-1 ),
,6b
6a,6b
1ꢀ, 2
0
.23 (dd, 1H, J
0
¼ 3.7, J
0
¼ 10.4 Hz, H-2 ), 4.04 (dd, 1H, J
0
¼ 10.4, J
0
¼
1ꢀ, 2
2ꢀ, 3
2ꢀ, 3
3ꢀ, 4
0
0
.9 Hz, H-3 ), 3.72 (dd, 1H, J
1.0, J 5ꢀ, 6 ꢀa ¼ 7.1, J
0
¼ 2.9, J
0
¼ 1.0 Hz, H-4 ), 4.33 (ddd, 1H, J
0
3
ꢀ, 4
4ꢀ, 5
0
4ꢀ, 5
¼
¼ 5.0 Hz, H-5 ), 3.78 (dd, 1H, J
¼ 7.1, J
¼
5ꢀ, 6 bꢀ
5ꢀ, 6 ꢀa
6 ꢀa ,6 bꢀ
9
.6 Hz, H-6 ꢀa ), 3.52 (dd, 1H, J
¼ 5.0, J
¼ 9.6 Hz, H-6 bꢀ) , 4.29(2), 4.43,
5ꢀ, 6 bꢀ
6 ꢀa ,6 bꢀ
4
.49, 4.53, 4.66(2), 5.03 (4 AB, 8H, 4 x OCH Aryl). Calcd. for C H O
2 40 42 9
(
666.77): C, 72.06; H, 6.35. Found: C, 72.81; H, 6.42.
2
0
1
Compound 7: colorless sirup, [a]D ¼ ꢀ5.5 (c ¼ 1.7, CHCl ); H NMR
3
(
3
300 MHz, C D ): d ¼ 7.02–7.51 (m, 20H, Aryl-H), 5.36 (d, 1H, J
¼
6
6
1,2
.1 Hz, H-1), 2.80 (dd, 1H, J1,2 ¼ 3.1, J ¼ 3.8 Hz, H-2), 3.38 (m, 1H, H-
2,3
3
), 3.67 (m, 1H, H-4), 4.20 (dd, 1H, J
¼ 2.1, J
¼ 7.2 Hz, H-5), 3.47
5
,6a
5,6b
(
dd, 1H, J5,6a ¼ 2.1, J
¼ 7.2 Hz, H-6a), 3.34 (dd, 1H, J
¼ 7.2, J
6a,6b
5,6b
6a,6b
0
¼
7.2 Hz, H-6b), 4.35 (d, 1H, J
0
¼ 7.7 Hz, H-1 ), 4.12 (dd, 1H, J
0
¼ 7.7,
1ꢀ, 2
1ꢀ, 2
0
0
J
2
0
¼ 9.8 Hz, H-2 ), 3.43 (dd, 1H, J
0
¼ 9.8, J
0
¼ 3.0 Hz, H-3 ), 3.86 (dd,
ꢀ, 3
2ꢀ, 3
3ꢀ, 4
0
0
1
H, J
7.2, J6
0
¼ 3.0, J
0
¼ 0.7 Hz, H-4 ), 3.50 (m, 1H, H-5 ), 3.73 (dd, 1H, J
3
ꢀ, 4
4ꢀ, 5
5ꢀ, 6 ꢀa
¼
¼ 9.0 Hz, H-6 ꢀa ), 3.64 (dd, 1H, J
¼ 5.7, J
¼ 9.0 Hz, H-
ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6bꢀ
6
b ꢀ) , 4.28, 4.34, 4.58, 4.62, 4.68,4.73, 5.06, 5.08 (4 AB, 8H, 4 x OCH Aryl).
2
Calcd. for C H O (666.77): C, 72.06; H, 6.35. Found: C, 72.18; H, 6.49.
4
0
42 9
1
,6:2,3-Dianhydro-4-O-(a-D-galactopyranosyl)-b-D-mannopyranose (8)
Compound 6 (900 mg, 1.35 mmol) dissolved in methanol (15 mL) were
ꢁ
hydrogenated with palladium/charcoal (100 mg, 10% Pd) for 12 h at 40 C.
Following filtration via celite and evaporation 376 mg (91%) of compound
2
0
8
were obtained as colorless sirup, [a]D ¼ þ 106.1 (c ¼ 0.77, CH OH),
3
which was directly used for the subsequent reaction.
1
,6-Anhydro-2-azido-3-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-galacto-
pyranosyl)- 2-deoxy-b-D-glucopyranose (10)
Compound 8 (376 mg, 1.23 mmol) dissolved in ethanol/water (4:1, 10 mL)
were refluxed with sodium azide (500 mg, 7.7 mmol) and ammonium chlor-
ide (500 mg, 9.4 mmol) for 6 h. The cold solution was filtered, evaporated
and dried in vaccuo to give raw 9. The material was peracetylated accord-
ing to GP1 and worked up. Purification from considerable amount of

JOURNAL OF CARBOHYDRATE CHEMISTRY
9
degradation products was by chromatography (toluene/ethyl acetate 1:1) to
ꢁ
20
give 190 mg (28%) of 10 as colorless crystals, mp 147 C, [a] ¼ þ 106.9
D
1
(
c ¼ 1.76, CDCl ); H NMR (300 MHz, C D ): d ¼ 5.29 (m, 1H, H-1), 2.70
3
6 6
(
m, 1H, H-2), 4.98 (m, 1H, H-3), 3.04 (m, 1H, H-4), 4.48 (m, 1H, H-5),
3
.39 (dd, 1H, J5,6a ¼ 1.3, J
¼ 7.7 Hz, H-6a), 3.34 (dd, 1H, J
¼ 5.7,
6a,6b
5,6b
0
J6a,6b ¼ 7.7 Hz, H-6b), 5.57 (d, 1H, J
0
¼ 3.9 Hz, H-1 ), 5.53 (dd, 1H, J
0
1ꢀ, 2
1ꢀ, 2
0
0
¼
3.9, J2
0
¼ 10.9 Hz, H-2 ), 5.93 (dd, 1H, J
0
¼ 10.9, J
0
¼ 3.3 Hz, H-3 ),
ꢀ, 3
2ꢀ, 3
0
3ꢀ, 4
0
5
1
1
.78 (dd, 1H, J
H, J 5ꢀ, 6 ꢀa ¼ 6.6, J
0
¼ 3.3, J
0
¼ 1.1 Hz, H-4 ), 4.53 (m, 1H, H-5 ), 4.24 (dd,
3ꢀ, 4
4ꢀ, 5
¼ 11.3 Hz, H-6 ꢀa ), 4.13 (dd, 1H, J
¼ 6.0, J
¼
6 ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6bꢀ
1.3 Hz, H-6bꢀ), 1.50, 1.63(2), 1.75, 2.00 (each s, each 3H, 5 x OAc). Calcd.
for C H N O (559.48): C, 47.23; H, 5.22; N, 7.51. Found: C, 46.35; H,
22
29 3 14
5.36; N, 7.65.
2
-Acetamido-3-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-galactopyranosyl)-1,6-
anhydro-2-deoxy-b-D-glucopyranose (12)
Method A
Compound 10 (160 mg, 0.29 mmol) dissolved in acetic acid (5 mL) were
ꢁ
hydrogenated with palladium/charcoal (100 mg, 10% Pd) for 12 h at 40 C.
Following filtration via celite and evaporation the raw material 11 was per-
acetylated according to GP1 and worked up. Purification was by chromato-
graphy (ethyl acetate) to give 127 mg (77%) of 12 as colorless crystals.
Method B
Compound 8 (320 mg, 1.04 mmol) dissolved concentrated aqueous ammonia
ꢁ
solution (10 mL) were heated in an autoclave for 24 h at 100 C. The solvent
was evaporated and the residue peracetylated according to GP1 and worked
up. The material was crystallized from ethyl acetate/petroleum ether to give
ꢁ
20
4
80 mg (80%) of 12 as colorless crystals, mp 86 C, [a] ¼ þ 40.6
D
1
(
(
(
c ¼ 0.85, CHCl ); H NMR (300 MHz, CDCl ): d ¼ 5.41 (s, 1H, H-1), 4.10
3
3
d, 1H, J2
¼ 9.6 Hz, H-2), 4.58 (m, 1H, H-3), 3.54 (m, 1H, H-4), 4.63
,NH
dd, 1H, J5,6a ¼ 0.5, J
¼ 5.7 Hz, H-5), 4.05 (dd, 1H, J
¼ 0.5, J
¼
5,6b
5,6a
6a,6b
7
.7 Hz, H-6a), 3.83 (dd, 1H, J5,6b ¼ 5.7, J
¼ 7.7 Hz, H-6b), 6.04 (d, 1H,
6a,6b
0
J2,NH ¼ 9.6 Hz, NH), 5.34 (d, 1H, J
0
¼ 3.7 Hz, H-1 ), 5.20 (dd, 1H, J
0
¼
1ꢀ, 2
1ꢀ, 2
0
0
3
5
.7, J2
.48 (dd, 1H, J
0
¼ 11.1 Hz, H-2 ), 5.41 (dd, 1H, J
0
¼ 11.1, J
0
¼ 3.3 Hz, H-3 ),
ꢀ, 3
2ꢀ, 3
0
3ꢀ, 4
0
¼ 3.3, J
0
¼ 1.2 Hz, H-4 ), 4.53 (ddd, 1H, J
0
¼ 1.2, J
3
ꢀ, 4
4ꢀ, 5
4ꢀ, 5
5ꢀ, 6 ꢀa
0
¼
6.0, J 5ꢀ, 6 bꢀ ¼ 7.0 Hz, H-5 ), 4.14 (dd, 1H, J
¼ 6.0, J
¼ 11.6 Hz, H-6 ꢀa ),
5ꢀ, 6 ꢀa
6 ꢀa ,6 bꢀ
4
2
5
.08 (dd, 1H, J
¼ 7.0, J
¼ 11.6 Hz, H-6 bꢀ ), 2.01, 2.04, 2.05, 2.09, 2.11,
5
ꢀ, 6 bꢀ
6 ꢀa ,6 bꢀ
.17 (each s, each 3H, 5 x OAc, NAc). Calcd. for C H NO (575.52): C,
2
4
33
15
0.09; H, 5.78; N, 2.43. Found: C, 50.34; H, 6.01; N, 2.10.

1
0
J. THIEM AND M. WIESNER
2
-Acetamido-1,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-a-D-galacto-
pyranosyl)-2-deoxy-a-D-glucopyranose (Octaacetyl-isolactosamine,13)
Compound 12 (420 mg, 0.73 mmol) dissolved in acetic anhydride (10 mL)
ꢁ
was stirred with boron trifluoride-etherate (0.5 mL) for 3 h at 20 C. The
mixture was poured into ice-cold saturated aqueous sodium hydrogen car-
bonate, stirred for 30 min and extracted with ethyl acetate. The organic
phase was washed with water, dried (MgSO4), evaporated and the raw
material purified by chromato-graphy (toluene/ethyl acetate 4:1) to give
ꢁ
20
3
(
4
4
9
10 mg (63%) of 13 as colorless crystals, mp 188 C, [a] ¼ þ 112.9
D
1
c ¼ 2.14, CHCl ); H NMR (300 MHz, CHCl ): d ¼ 5.54 (d, 1H, J
¼
3
3
1,2
.0 Hz, H-1), 4.39 (ddd, 1H, J ¼ 4.0 J ¼ 11.1, J
¼ 9.6 Hz, H-2),
1
,2
2,3
2,NH
.58 (dd, 1H, J2,3 ¼ 11.1, J ¼ 9.0 Hz, H-3), 4.07 (m, 1H, J ¼ 9.0, J
¼
3,4
3,4
4,5
.6 Hz H-4), 4.00 (m, 1H, H-5), 4.43 (dd, 1H, J5,6a ¼ 2.4, J
¼ 12.4 Hz,
6a,6b
H-6a), 4.19 (dd, 1H, J5,6b ¼ 4.0, J
¼ 12.4 Hz, H-6b), 5.51 (d, 1H, J
6a,6b
2,NH
0
¼
9.6 Hz, NH), 6.09 (d, 1H, J
0
¼ 3.5 Hz, H-1 ), 5.15 (dd, 1H, J
0
¼ 3.5,
1ꢀ, 2
1ꢀ, 2
0
0
J
2
0
¼ 11.0 Hz, H-2 ), 5.28 (dd, 1H, J
0
¼ 11.9, J
0
3ꢀ, 4
¼ 3.1 Hz, H-3 ), 5.44
ꢀ, 3
2ꢀ, 3
0
0
(
dd, 1H, J3
0
¼ 3.1, J
0
¼ 1.0 Hz, H-4 ), 4.17 (m, 1H, H-5 ), 4.11 (dd, 1H,
ꢀ, 4
4ꢀ, 5
J
5
¼ 1.5, J
¼ 12.6 Hz, H-6 ꢀa ), 4.08 (dd, 1H, J
¼ 6.0, J
¼
ꢀ, 6 ꢀa
6 ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6 bꢀ
1
2.6 Hz, H-6bꢀ), 1.92, 1.99, 2.06(2), 2.07, 2.11, 2.14, 2.23 (each s, each 3H, 7
x OAc, NAc). Calcd. for C H NO (677.61): C, 49.63; H, 5.80; N, 2.07.
2
8
39
18
Found: C, 49.13; H, 5.71; N, 1.91.
2
-Acetamido-2-deoxy-4-O-(a-D-galactopyranosyl)-a-D-glucopyranose (N-Acetyl-
isolactosamine,14)
Compound 13 (200 mg, 0.30 mmol) dissolved in anhydrous methanol
(
1
H
10 mL) was treated with sodium methylate in anhydrous methanol (1%,
ꢁ
mL) for 4 h at 20 C. Following neutralization with Amberlite IRA 120,
þ
the residue was freeze dried to give 105 mg (93%) of 14 as colorless
ꢁ
20
amorphous material, softening interval 180–185 C, [a] ¼ þ 138.1
D
ꢁ
[
24]
20
(
1
5 min) ! þ 125.9 (6 h) (c ¼ 0.82, H O); lit.
mp 193–195 C, [a] ¼ þ
2
D
47 (2 min) ! þ 131 (3 h) (c ¼ 0.5, H O/CH OH 9:1).
2
3
1
,6-Anhydro-2-azido-3-O-(methyl 2,3,4-tri-O-acetyl-b-D-glucopyranosyl-
uronate)-4-O-benzyl-2-deoxy-b-D-glucopyranose (17)
[39]
Methyl 2,3,4-tri-O-acetyl-b-D-glucopyranosyluronate fluoride (15,
550 mg,
1
.64 mmol) and 1,6-anhydro-2-azido-4-O-benzyl-2-deoxy-b-D-glucopyranose
[33]
(16,
454 mg, 1.64 mmol) dissolved in anhydrous dichloromethane (10 mL)
were treated with boron trifluoride-etherate (0.83 mL, 6.5 mmol) and molecular
ꢁ
sieve 3 A (59 mg) for 2 h at 20 C. The mixture was poured onto ice water,
extracted with dichloromethane, dried (MgSO ), evaporated and purified by
4

JOURNAL OF CARBOHYDRATE CHEMISTRY
11
chromatography (dichloromethane/ethyl acetate 20: 1) to give 650 mg (67%) of
ꢁ
20
1
3
7, which crystallized from ethylacetate/n-hexane; mp 147–149 C, [a] ¼ þ
D
1
9.9 (c¼ 0.5, CHCl ); H NMR (300 MHz, CDCl ): d ¼ 7.29–7.41 (m, 5H, Aryl-
3
3
H), 5.51 (m, 1H, H-1), 2.98 (m, 1H, H-2), 4.01 (m, 1H, H-3), 3.50 (m, 1H, H-
4
¼
J
), 4.58 (dd, 1H, J5,6a ¼ 0.8, J ¼ 6.0 Hz, H-5), 3.89 (dd, 1H, J ¼ 0.8, J
5,6b
5,6a
6a,6b
7.6 Hz, H-6a), 3.66 (dd, 1H, J
¼ 6.0, J
¼ 7.6 Hz, H-6b), 4.55 (d, 1H,
5,6b
6a,6b
0
0
0
¼ 8.0 Hz, H-1 ), 5.01(dd, 1H, J
0
¼ 8.0, J
0
¼ 9.6 Hz, H-2 ), 5.16 (dd, 1H,
1
ꢀ, 2
1ꢀ, 2
2ꢀ, 3
0
0
J
0
¼ 9.6, J
0
¼ 9.5 Hz, H-3 ), 5.27 (dd, 1H, J
0
¼ 9.5, J
0
¼ 9.7 Hz, H-4 ),
2
ꢀ, 3
3ꢀ, 4
3ꢀ, 4
4ꢀ, 5
0
4.53 (m, 1H, H-5 ), 4.63, 4.72 (AB, 2H, OCH Aryl), 3.75 (s, 3H, OCH ), 2.03,
2
3
2.04, 2.05 (each s, each 3H, 3 x OAc). Calcd. for C H N O (593.54): C,
26 31 3 13
52.61; H, 5.26; N, 7.08. Found: C, 52.22; H, 5.13; N, 6.30.
2
-Acetamido-3-O-(methyl 2,3,4-tri-O-acetyl-b-D-glucopyranosyluronate)-4-O-
acetyl-1,6-anhydro-2-deoxy-b-D-glucopyranose (19)
Compound 17 (391 mg, 0.66 mmol) dissolved in acetic acid (10 mL) were
ꢁ
hydrogenated with palla-dium/charcoal (100 mg, 10% Pd) for 15 h at 40 C.
Following filtration via celite and evaporation the raw material 18 was per-
acetylated according to GP1 and worked up. Purification was by chroma-
tography (ethyl acetate) and crystalli-sation from ethyl acetate/n-hexane to
ꢁ
20
give 252 mg (68%) of 19 as colorless crystals; mp 224 C, [a] ¼ ꢀ70.0
D
1
(
c ¼ 1.41, CHCl ); H NMR (300 MHz, CDCl ): d ¼ 5.341 (m, 1H, H-1),
3
3
3
.91 (m, 1H, H-2), 3.68 (m, 1H, H-3), 4.83 (m, 1H, H-4), 4.59 (dd, 1H,
J5,6a ¼ 0.8, J
¼ 6.0 Hz, H-5), 4.10 (dd, 1H, J
¼ 0.8, J
¼ 8.0 Hz,
5,6b
5,6a
6a,6b
H-6a), 3.70 (dd, 1H, J
¼ 6.0, J
¼ 8.0 Hz, H-6b), 5.87 (d, 1H, J
¼
5
,6b
6a,6b
2,NH
0
9.3 Hz, NH), 4.87 (d, 1H, J1
0
¼ 8.0 Hz, H-1 ), 5.07(dd, 1H, J
0
¼ 8.0, J
0
ꢀ, 2
1ꢀ, 2
2ꢀ, 3
0
0
¼
9.6 Hz, H-2 ), 5.33 (dd, 1H, J
0
¼ 9.6, J
0
¼ 9.6 Hz, H-3 ), 5.18 (dd,
2ꢀ, 3
3ꢀ, 4
0
0
1
3
H, J 3ꢀ, 4
0
¼ 9.6, J
0
¼ 10.0 Hz, H-4 ), 4.10 (d, 1H, J
0
¼ 10.0 Hz, H-5 ),
4ꢀ, 5
4ꢀ, 5
.74 (s, 3H, OCH ), 2.02(2), 2.08, 2.12, 2.17 (each s, each 3H, 4 x OAc,
3
NAc). Calcd. for C H NO (561.49): C, 49.20; H, 5.57; N, 2.49. Found:
2
3
31
15
C, 49.12; H, 5.44; N, 2.27.
2
-Acetamido-1,4,6-tri-O-acetyl-3-O-(methyl 2,3,4-tri-O-acetyl-b-D-glucopyran-
osyluronate)-2-deoxy-a-D-glucopyranose (20)
Compound 19 (220 mg, 0.39 mmol) dissolved in acetic anhydride (5 mL)
ꢁ
was stirred with boron trifluoride-etherate (0.5 mL) for 2 h at 20 C. The
mixture was poured into ice-cold saturated aqueous sodium hydrogen car-
bonate, stirred for 30 min and extracted with dichloromethane. The organic
phase was washed with water, dried (MgSO ) and evaporated. The raw
4
material was purified by chromato-graphy (ethyl acetate) and crystallized
from ethanol to give 195 mg (75%) of 20 as colorless crystals, mp

1
2
J. THIEM AND M. WIESNER
ꢁ
20
[31]
ꢁ
24
1
17–118 C, [a] ¼ þ 24.2 (c ¼ 1.05, CHCl ); lit. : mp 120 C, [a]
¼
D
3
D
[
32]
ꢁ
23
þ 24.5 (c ¼ 2, CHCl ); lit. : mp 215–217 C, [a] ¼ þ 20 (c ¼ 0.98,
3
D
1
CHCl ); H NMR (300 MHz, (CD ) CO): d ¼ 5.96 (d, 1H, J ¼ 3.7 Hz, H-
3
3 2
1,2
1
1
), 4.41 (ddd, 1H, J ¼ 3.7, J ¼ 10.8, J
¼ 9.7 Hz, H-2), 4.17 (dd,
1
,2
2,3
2,NH
H, J2,3 ¼ 10.8, J ¼ 9.3 Hz, H-3), 5.03 (dd, 1H, J ¼ 9.3, J ¼ 10.1 Hz,
3,4
3,4
4,5
H-4), 4.07 (ddd, 1H, J ¼ 10.1, J
¼ 4.1, J
¼ 2.2 Hz, H-5), 4.18 (dd,
4
,5
5,6a
5,6b
1
1
H, J5,6a ¼ 4.1, J
¼ 12.2 Hz, H-6a), 4.19 (dd, 1H, J
¼ 2.2, J
¼
6a,6b
5,6b
6a,6b
2.2 Hz, H-6b), 7.34(d, 1H, J
¼ 9.7 Hz, NH), 5.09 (d, 1H, J
0
¼ 8.1 Hz,
0
2
,NH
1ꢀ, 2
0
0
H-1 ), 4.84 (dd, 1H, J
0
¼ 8.1, J
0
¼ 9.8 Hz, H-2 ), 5.22 (dd, 1H, J
¼
1
0
ꢀ, 2
2ꢀ, 3
2ꢀ, 3
0
9.8, J 3ꢀ, 4
0
¼ 9.7 Hz, H-3 ), 5.05 (dd, 1H, J
0
¼ 9.7, J
0
¼ 9.8 Hz, H-4 ), 4.19
3ꢀ, 4
4ꢀ, 5
0
(
2
d, 1H, J4
0
¼ 9.8 Hz, H-5 ), 3.73 (s, 3H, OCH ), 1.94, 1.96, 1.98, 2.00, 2.01,
ꢀ, 5
3
.09, 2.11 (each s, each 3H, 6 x OAc, NAc).
Benzyl 2,3,4-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-D-glucopyranosyl)-b-D-
galactopyranoside(23) and benzyl 2,3,4-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-b-D-glucopyranosyl)-b-D-galactopyranoside(24)
[
34]
Compound 21
(550 mg, 1.01 mmol) and benzyl 2,3,6-tri-O-benzyl-b-D-
[
24]
galactopyranoside (22,
548 mg, 1.01 mmol) dissolved in anhydrous ether
(
10 mL) were treated with titanium tetrafluoride (60 mg, 0.48 mmol) for 3 h
ꢁ
at 0 C and worked up according to GP2. The raw material (913 mg, 85%)
1
contained a mixture of anomers a(23): b(24) ¼ 55: 45 according to H
NMR. Separation was by chromatography (chloroform/ethyl acetate 100:1).
2
0
Compound 23: 316 mg (29%), colorless sirup, [a]D ¼ þ 51.2 (c ¼ 1.5,
1
CHCl ); H NMR (300 MHz, C D ): d ¼ 7.03–7.42 (m, 40H, Aryl-H), 4.43
3
6 6
(
(
d, 1H, J1 ¼ 7.7 Hz, H-1), 4.11 (dd, 1H, J ¼7.7, J ¼ 9.9 Hz, H-2), 3.31
,2
1,2
2,3
dd, 1H, J2,3 ¼9.9, J ¼ 2.9 Hz, H-3), 4.10 (dd, 1H, J ¼2.9, J ¼ 0.5 Hz,
3,4
3,4
4,5
H-4), 4.18 (m, 1H, H-5), 3.72 (dd, 1H, J
¼ 9.3, J
¼ 6.4 Hz, H-6a),
5
,6a
6a,6b
3
.35 (dd, 1H, J
¼ 7.2, J
¼ 6.4 Hz, H-6b), 5.19 (d, 1H, J
0
¼ 3.5 Hz,
5
,6b
6a,6b
1ꢀ, 2
0
0
H-1 ), 3.61 (dd, 1H, J
0
¼ 3.5, J
0
¼ 9.9 Hz, H-2 ), 4.38 (dd, 1H, J
0
¼
1
ꢀ, 2
0
2ꢀ, 3
2ꢀ, 3
0
9
4
J
.9, J 3ꢀ, 4
0
¼ 9.2 Hz, H-3 ), 4.06 (dd, 1H, J
0
¼ 9.2, J
0
¼ 10.1 Hz, H-4 ),
3ꢀ, 4
4ꢀ, 5
0
.57 (ddd, 1H, J
¼ 0.5, J
0
¼ 10.1, J
¼ 0.5, J
¼ 1.6 Hz, H-5 ), 3.70 (dd, 1H,
4ꢀ, 5
5ꢀ, 6 ꢀa
5ꢀ, 6bꢀ
¼ 11.0 Hz, H-6 ꢀa ), 3.45 (dd, 1H, J
¼ 1.6, J
¼
5
ꢀ, 6 ꢀa
6 ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6 bꢀ
1
4
1.0 Hz, H-6bꢀ), 4.21, 4.25, 4.27, 4.29, 4.44, 4.54, 4.57, 4.72, 4.73, 4.74, 4.80,
.82, 4.85, 4.89, 4.98, 4.99 (8 AB, 16H, 8 x OCH Aryl). Calcd. for
2
C H O (1063.3): C, 76.81; H, 6.64. Found: C, 76.40; H, 6.17.
6
8
70 11
2
0
Compound 24: 259 mg (24%), colorless sirup, [a]D ¼ þ 13.5 (c ¼ 1.42,
1
CHCl ); H NMR (300 MHz, C D ): d ¼ 7.00–7.56 (m, 40H, Aryl-H), 4.53
3
6 6
(
(
d, 1H, J1 ¼ 7.7 Hz, H-1), 4.14 (dd, 1H, J ¼7.7, J ¼ 9.8 Hz, H-2), 3.41
,2
1,2
2,3
dd, 1H, J2,3 ¼9.8, J ¼ 2.8 Hz, H-3), 4.30 (dd, 1H, J ¼2.8, J ¼ 0.7 Hz,
3,4
3,4
4,5
H-4), 3.57 (m, 1H, H-5), 4.15 (dd, 1H, J
¼ 4.7, J
¼ 10.3 Hz, H-6a),
5
,6a
6a,6b
4
.07 (dd, 1H, J5,6b ¼ 6.3, J6a,6b ¼ 10.3 Hz, H-6b), 5.26 (d, 1H, J 1ꢀ, 2 ¼
0

JOURNAL OF CARBOHYDRATE CHEMISTRY
13
0
0
7
.7 Hz, H-1 ), 3.65 (dd, 1H, J
0
¼ 7.7, J
0
¼ 9.0 Hz, H-2 ), 3.74 (m, 4H,
1ꢀ, 2
2ꢀ, 3
0
0
H-3 , ꢀ4 , -6 ꢀa , ꢀ6 bꢀ), 3.52 (ddd, 1H, J
0
¼ 9.6, J
¼ 2.1, J
¼ 4.5 Hz,
4ꢀ, 5
5ꢀ, 6 ꢀa
5ꢀ, 6bꢀ
0
H-5 ), 4.41, 4.47, 4.60, 4.63, 4.66(2), 4.69, 4.70, 4.73, 4.74, 4.8(2), 4.94,
5
.00(2), 5.07, 5.39 (8 AB, 16H, 8 x OCH Aryl). Calcd. for C H O
2 68 70 11
(
1063.3): C, 76.81; H, 6.64. Found: C, 76.21; H, 6.28.
Benzyl 2,3,4-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-D-galactopyranosyl)-
b-D-galactopyranoside(25) and benzyl 2,3,4-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-b-D-galactopyranosyl)-b-D-galactopyranoside(26)
[
25]
Compound 1
topyranoside (22,
(420 mg, 0.77 mmol) and benzyl 2,3,6-tri-O-benzyl-b-D-galac-
[24]
420 mg, 0.77 mmol) dissolved in anhydrous ether (10 mL)
ꢁ
were treated with titanium tetrafluoride (560 mg, 0.40 mmol) for 3 h at 0 C
and worked up according to GP2. The raw material (667 mg, 81%) contained
1
a mixture of anomers a(25): b(26) ¼ 65: 35 according to H NMR.
Separation was by chromatography (chloroform/ethyl acetate 50:1).
2
0
Compound 25: 346 mg (42%), colorless sirup, [a] ¼ þ 35.0 (c ¼ 0.99,
D
[
35]
1
CHCl ); lit. : sirup, [a] ¼ þ 38 (c ¼ 1.0, CHCl ); H NMR (300 MHz,
3
3
C D ): d ¼ 7.03–7.48 (m, 40H, Aryl-H), 4.44 (d, 1H, J ¼ 7.7 Hz, H-1),
6
6
1,2
4
3
.15 (m, 3H, H-2, ꢀ4, ꢀ5), 3.34 (dd, 1H, J ¼10.1, J ¼ 3.0 Hz, H-3),
2
,3
3,4
.69 (dd, 1H, J
¼ 9.4, J
¼ 6.0 Hz, H-6a), 3.32 (dd, 1H, J
¼ 8.0,
5
,6a
6a,6b
5,6b
0
J6a,6b ¼ 6.03 Hz, H-6b), 5.26 (d, 1H, J
0
¼ 3.4 Hz, H-1 ), 4.37 (dd, 1H, J
0
1ꢀ, 2
1ꢀ, 2
0
0
¼
3.4, J2
0
¼ 10.1 Hz, H-2 ), 4.27 (dd, 1H, J
0
¼ 10.1, J
0
¼ 2.7 Hz, H-3 ),
ꢀ, 3
2ꢀ, 3
0
3ꢀ, 4
0
4
1
8
5
.20 (dd, 1H, J
0
¼ 2.7, J
0
¼ 0.8 Hz, H-4 ), 4.81 (m, 1H, H-5 ), 3.94 (dd,
3ꢀ, 4
4ꢀ, 5
H, J 5ꢀ, 6 ꢀa ¼ 9.0, J
¼ 8.4 Hz, H-6 ꢀa ), 3.55 (dd, 1H, J
¼ 5.0, J
¼
6 ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6bꢀ
.4 Hz, H-6bꢀ), 4.15(4), 4.42(2), 4.49, 4.55, 4.58, 4.65, 4.83, 4.90(2), 4.99,
.05, 5.16 (8 AB, 16H, 8 x OCH Aryl).
2
2
0
Compound 26: 185 mg (22%), colorless sirup, [a]D ¼ þ 5.4 (c ¼ 2.59,
1
CHCl ); H NMR (300 MHz, C D ): d ¼ 7.03–7.57 (m, 40H, Aryl-H), 4.49
3
6 6
(
d, 1H, J1 ¼ 7.8 Hz, H-1), 4.13 (dd, 1H, J ¼7.8, J ¼ 9.9 Hz, H-2), 3.36
,2
1,2
2,3
(
dd, 1H, J2,3 ¼9.9, J ¼ 2.7 Hz, H-3), 4.39 (dd, 1H, J ¼2.7, J ¼ 0.8 Hz,
3,4
3,4
4,5
H-4), 3.47 (ddd, 1H, J ¼ 0.8, J
¼ 6.0, J
¼6.0 Hz, H-5), 4.01(dd, 1H,
4
,5
5,6a
5,6b
J5,6a ¼ 6.0, J
¼ 10.0 Hz, H-6a), 3.88 (dd, 1H, J
¼ 6.0, J
¼
6a,6b
5,6b
6a,6b
0
1
0.0 Hz, H-6b), 5.20 (d, 1H, J
0
¼ 7.7 Hz, H-1 ), 4.10 (dd, 1H, J
0
¼ 7.7,
1ꢀ, 2
1ꢀ, 2
0
0
J
2ꢀ, 3
0
¼ 9.8 Hz, H-2 ), 3.37 (dd, 1H, J
0
¼ 9.8, J
0
¼ 2.8 Hz, H-3 ), 3.73 (dd,
2ꢀ, 3
3ꢀ, 4
0
0
1H, J
0
¼ 2.8, J
0
¼ 1.0 Hz, H-4 ), 3.45 (m, 1H, H-5 ), 3.71 (dd, 1H, J
3ꢀ, 4
4ꢀ, 5
5ꢀ, 6 ꢀa
¼
7.1, J6
¼ 9.1 Hz, H-6 ꢀa ), 3.65 (dd, 1H, J
¼ 5.9, J
¼ 9.1 Hz, H-
ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6bꢀ
6
4
b ꢀ) , 4.30, 4.35, 4.47, 4.48, 4.49, 4.57, 4.58, 4.60, 4.61, 4.66, 4.67, 4.78, 4.94,
.95, 5.07, 5.31 (8 AB, 16H, 8 x OCH Aryl). Calcd. for C H O
2
68 70 11
(
1063.30): C, 76.81; H, 6.64. Found: C, 76.12; H, 5.22.

1
4
J. THIEM AND M. WIESNER
4
-O-(a-D-Galactopyranosyl)-b-D-galactopyranose(27)
Compound 25 (322 mg, 0.30 mmol) dissolved in methanol (10 mL) were
ꢁ
hydrogenated with palladium/charcoal (100 mg, 10% Pd) for 16 h at 40 C.
Following filtration via celite and evaporation 95 mg (92%) of compound
2
7 were obtained as colorless amorphous material, softening point
ꢁ
20
[35]
100–105 C [a] ¼ þ 148.1 (c ¼ 1.17, H O); lit. : [a]¼ þ 163 (c ¼ 1,
D
[38] 26
2
H O); lit. : [a]D ¼ þ 170 (c ¼ 1, H O).
2
2
Benzyl 2,3,4-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-a-D-galactopyranosyl)-
b-D-glucopyranoside(29) and benzyl 2,3,4-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-b-D-galactopyranosyl)-b-D-glucopyranoside (30)
[
25]
Compound 1
(515 mg, 0.95 mmol) and benzyl 2,3,4-tri-O-benzyl-b-D-
[
26]
glucopyranoside (28,
514 mg, 0.95 mmol) dissolved in anhydrous ether
(
10 mL) were treated with titanium tetrafluoride (50 mg, 0.40 mmol) for 3 h
ꢁ
at 0 C and worked up according to GP2. The raw material (858 mg, 85%)
1
contained a mixture of anomers a(29): b(30) ¼ 62: 38 according to H
NMR. Separation was by chromatography (toluene/ethyl acetate 40:1).
2
0
Compound 29: 282 mg (36%), colorless sirup, [a]D ¼ þ 15.2 (c ¼ 2.11,
1
CHCl ); H NMR (300 MHz, C D ): d ¼ 7.01–7.45 (m, 40H, Aryl-H), 4.42
3
6 6
(
(
d, 1H, J1 ¼ 7.9 Hz, H-1), 3.63 (dd, 1H, J ¼7.9, J ¼ 9.1 Hz, H-2), 4.95
,2
1,2
2,3
dd, 1H, J2,3 ¼9.1, J ¼ 8.6 Hz, H-3), 4.31 (dd, 1H, J ¼8.6, J ¼ 9.6 Hz,
3,4
3,4
4,5
H-4), 3.47 (ddd, 1H, J ¼ 9.6, J
¼ 4.3, J
¼2.4 Hz, H-5), 3.98 (dd,
4
,5
5,6a
5,6b
1
1
4
H, J5,6a ¼ 4.3, J
¼ 11.0 Hz, H-6a), 3.92 (dd, 1H, J
¼ 2.4, J
¼
6a,6b
5,6b
6a,6b
0
0
0
1.0 Hz, H-6b), 6.04 (d, 1H, J
0
ꢀ, 2
¼ 3.7 Hz, H-1 ), 4.27 (m, 2H, H-2 , ꢀ5 ),
1
0
0
.16 (dd, 1H, J 2ꢀ, 3
0
¼ 11.0, J
0
¼ 2.8 Hz, H-3 ), 4.16 (m, 1H, H-4 ), 3.82
3ꢀ, 4
(
dd, 1H, J 5ꢀ, 6 ꢀa ¼ 7.8, J
¼ 8.7 Hz, H-6 ꢀa ), 3.76 (dd, 1H, J
¼ 5.7, J
6 ꢀa ,6bꢀ
5ꢀ, 6bꢀ
6 ꢀa ,6bꢀ
¼
8.7 Hz, H-6bꢀ), 4.23, 4.30, 4.40, 4.51, 4.52, 4.56, 4.57, 4.61, 4.64, 4.66(2),
4
.87, 4.95, 4.96, 5.03, 5.04 (8 AB, 16H, 8 x OCH Aryl). Calcd. for
2
C H O (1063.30): C, 76.81; H, 6.64. Found: C, 76.10; H, 6.31.
6
8
70 11
2
0
Compound 30: 173 mg (17%), colorless sirup, [a]D ¼ þ 2.7 (c¼ 0.91,
1
CHCl ); H NMR (300 MHz, C D ): d ¼ 7.07–7.52 and 7.68–7.73 (each m,
3
6 6
4
(
3
4
3
0
4
0H, Aryl-H), 4.47 (d, 1H, J ¼ 7.5 Hz, H-1), 3.66 (m, 3H, H-2, ꢀ3, -6 ꢀa ), 4.33
1
,2
dd, 1H, J3,4 ¼9.0, J ¼ 10.0Hz, H-4), 3.30 (m, 1H, H-5), 4.02 (dd, 1H, J
¼
4,5
5,6a
.7, J6a,6b ¼ 11.4Hz, H-6a), 3.78 (dd, 1H, J
¼ 1.4, J
¼ 11.4 Hz, H-6b),
5,6b
6a,6b
0
0
.71 (d, 1H, J
0
¼ 7.8 Hz, H-1 ), 4.03 (dd, 1H, J
0
¼ 7.8, J
0
¼ 9.9 Hz, H-2 ),
1
ꢀ, 2
1ꢀ, 2
2ꢀ, 3
0
.33 (dd, 1H, J
0
¼ 9.9, J
0
¼ 3.0 Hz, H-3 ), 3.84 (dd, 1H, J
0
¼ 3.0, J
0
¼
2ꢀ, 3
3ꢀ, 4
3ꢀ, 4
4ꢀ, 5
0
0
.5 Hz, H-4 ), 3.44 (m, 2H, H-5 , ꢀ6 bꢀ) , 4.18, 4.33, 4.39, 4.44, 4.51, 4.58(3), 4.79,
.83, 4.87, 4.89, 4.91, 5.023, 5.03, 5.32 (8 AB, 16H, 8 x OCH Aryl). Calcd. for
2
C H O (1063.30): C, 76.81; H, 6.64. Found: C, 76.33; H, 6.32.
68 70 11

JOURNAL OF CARBOHYDRATE CHEMISTRY
15
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