1,2-trans-glycosyl azides of sugar 2-sulfonic acids

Article abstract of DOI:10.1055/s-2005-872244

Treatment of the 2-O-mesylated 1-SAc-, 1-S[2-(trimethylsilyl)ethyl]- α-D-manno-, and 1-SAll-β-D-gluco-pyranosides with NaN₃ resulted exclusively in 2-SAc-, 2-S[2-(trimethylsilyl)ethyl]-β-D-gluco-, and 2-SAll-α-manno-pyranosyl azides. The 2-S su

Full text of DOI:10.1055/s-2005-872244

2242
LETTER
1,2-trans-Glycosyl Azides of Sugar 2-Sulfonic Acids
1
, 2-trans
-
Glyco
á
syl
A
zides
s
of Sugar
2
z
-Sulfonic
A
l
cids ó Lázár, István Bajza, Zsolt Jakab, András Lipták*
Research Group for Carbohydrates of the Hungarian Academy of Sciences, P.O. Box 55, 4010 Debrecen, Hungary
Fax +36(52)512913; E-mail: liptaka@puma.unideb.hu
Received 10 June 2005
episulfonium ion
oxocarbonium ion
O
Abstract: Treatment of the 2-O-mesylated 1-SAc-, 1-S[2-(trimeth-
ylsilyl)ethyl]-a-D-manno-, and 1-SAll-b-D-gluco-pyranosides with
NaN3 resulted exclusively in 2-SAc-, 2-S[2-(trimethylsilyl)ethyl]-
b-D-gluco-, and 2-SAll-a-manno-pyranosyl azides. The 2-S substit-
uents were removed either with acetic acid (SAc), or Hg(TFA)2
(SCH2CH2SiMe3, SCH=CHCH3) and the 2-SH groups were oxi-
dized into sugar 2-sulfonic acids giving 1,2-trans-glycosyl azides.
O
Nu–
O
Nu–
S
RS
S
R
Nu
R
– HNu
O
O
Nu
Key words: 1,2-thio-migration, 2-S substituents, glycosyl azides,
sugar 2-sulfonic acids
RS
RS
Scheme 2 The role of episulfonium and oxocarbonium ions in the
formation of the anomers and glycals.
Interest in carbohydrate derivatives is steadily increasing
because of their function in many biological processes.1
Part of our program is aimed at developing the regio- and With all four compounds 1–4 the reactions occurred re-
stereoselective chemical synthesis of sugar sulfonic acids, gio- and stereoselectively; the thio-aryl groups migrated
as well as glycosyl azides of sugar sulfonic acids based on to position 2 and the nucleophile entered at the anomeric
an intramolecular 1,2-thio-migration processes.2–4
centre.5 The regioselectivity of the reactions is unambigu-
ous. Concerning the stereoselectivity of the reaction, in all
four reactions and for both reaction centers complete in-
version of configuration took place.
Preconditions for the 1,2-thio-migration reactions are: i)
anomeric S-alkyl or S-aryl group; ii) a good leaving group
at C-2; and iii) trans arrangement of the substituents at C-
1 and C-2. The added nucleophile helps the formation of The reactions have to proceed through episulfonium inter-
either an episulfonium or an oxocarbonium ion intermedi- mediates, the theoretically possible oxocarbonium ion in-
ate. The nucleophile and the nucleophilic character of the termediates do not play any role in these reactions. The
thioaglycone play an important role in the determination thio-b-D-glucopyranoside derivatives resulted in a-D-
of the stereochemistry of the anomeric center, too, as mannopyranosides, while thio-a-D-mannopyranosides
demonstrated below.
furnished b-D-glucopyranosides (Scheme 1).
Treatment of gluco-compounds 1 and 2 or manno-deriva- The main advantage of the trityl derivatives is that the S-
tives 3 and 4 with an O-nucleophile (i.e. OCH3) gave trityl group can be directly oxidized into sulfonic acid ei-
products 5–8 in excellent yields.
ther by Oxone® or H2O2.
Treatment of compounds 1–4 with azide (NaN3 or
Me3SiN3) resulted in the formation of 2-SPh- or 2-STr-
a,b-gluco- or mannopyranosyl azides, indicating that the
1→2 thio-migration and glycosyl azide formation both
occurred regioselectively. The stereoselectivity of the re-
action was determined and both anomers were present.
Especially in the case of Me3SiN3 a considerable amount
of 2-SPh- or 2-STr-glycals were formed and isolated.
OL
O
O
SR
OL
SR
L = leaving
group
1 R = Ph
2 R = Tr
3 R = Ph
4 R = Tr
NaOCH3
NaOCH3
SR
The product distribution of the reaction mixture can only
be explained by the assumption that in the case of the
azide nucleophile, besides the episulfonium intermediate,
the oxocarbonium ion intermediate also plays a substan-
tial role. From the first intermediate only 1,2-trans-glyco-
sides can be formed. The oxocarbonium ion delivers both
anomers and the unwanted glycals are also generated
through the 1,2-cis anomers (Scheme 2).
O
O
OCH3
SR
OCH3
5 R = Ph
6 R = Tr
7 R = Ph
8 R = Tr
Scheme 1 The results of the 1,2-trans-thio-migration promoted by
NaOMe for phenyl and trityl thioglycopyranoside derivatives
Our aim is to prepare anomerically pure glycosyl azides of
sugar 2-sulfonic acids.6 To fulfill this we looked for rather
small, reactive, and easily transformable ‘thioglycosides’.
SYNLETT 2005, No. 14, pp 2242–2244
Advanced online publication: 26.07.2005
DOI: 10.1055/s-2005-872244; Art ID: G20205ST
© Georg Thieme Verlag Stuttgart · New York
0
2
.0
9
.2
0
0
5

LETTER
1,2-trans-Glycosyl Azides of Sugar 2-Sulfonic Acids
2243
Table 1 Characteristic 1H and 13C NMR Data of the Synthesized
Compounds
OH
OCOCH2Cl
O
BnO
BnO
BnO
BnO
BnO
BnO
a
O
b
OH
OCOCH2Cl
Com-
pound
J1,2
(Hz)
C-1
(ppm)
C-2
(ppm)
JC1-H1
(Hz)
Solvent
10 (83%)
9
13
14
15
20
21
22
23
24
28
30
32
1.8
9.6
6.1
ca. 1
9.9
4.1
6.3
4.0
9.3
1.4
ca. 1
80.7
88.8
89.1
84.5
92.0
91.5
89.5
90.8
85.0
91.8
89.5
–
–
CDCl3
CDCl3
CD3OD
CDCl3
CDCl3
CDCl3
CD3OD
CD3OD
CDCl3
CDCl3
CDCl3
OH
O
BnO
OCOCH2Cl
O
BnO
d
c
BnO
BnO
BnO
BnO
50.0
66.8
–
162.3
166.9
–
SAc
SAc
12 (73%)
11 (42%)
OMs
O
BnO
BnO
f
e
O
52.6
50.7
67.0
64.7
–
161.1
170.7
167.3
171.4
–
BnO
BnO
BnO
BnO
N3
SAc
14 (55%)
SAc
13
BnO
O
BnO
BnO
N3
SO3Na
15 (71%)
48.7
61.8
171.1
–
Scheme 3 Preparation of the 2-sulfonic acid sodium salt of b-D-glu-
copyranosyl azide derivative 15 by 1,2-trans-thio-migration of 1-
SAc-a-D-mannopyranose (13). Reagents and conditions: a)
O(COCH2Cl)2 (3 equiv), pyridine, –20 °C, 1.5 h; b) CH3COSH (1.5
equiv), BF3·Et2O (2 equiv), CH2Cl2, 8 h; c) thiourea (5 equiv), MeOH,
50 °C, 8 h; d) MsCl (1.5 equiv), pyridine, 2 h; e) NaN3 (10 equiv),
DMF, 25 °C, 1 h; f) H2O2 (10 equiv), NaOAc (1 equiv), CH3COOH,
40 °C, 24 h.
OH
O
OR
O
RO
O
Ph
b
d
O
RO
RO
RO
SiMe3
SiMe3
S
S
19 R = H (54%)
20 R = Bn (89%)
17 R = Ac (62%)
18 R = H (96%)
Therefore, first the 2-O-sulfonyl 1-SAc-glycopyranose
derivatives were selected. The starting compound was
3,4,6-tri-O-benzyl-a,b-D-mannopyranose7 (9) which was
chloroacetylated to give 10, and then transformed further
into the 1-SAc-a-D-mannopyranoside derivative 11. The
chloroacetyl substituent from O-2 was removed by
thiourea8 to give compound 12, which was mesylated
(→13) and then reacted with sodium azide to effect the
migration6 of the 1-SAc group. The isolated compound
proved to be the desired 2-SAc-b-D-glucopyranosyl azide
14 formed with complete regio- and stereoselectivity. Its
characteristic 1H and 13C NMR data verified the postulat-
ed structure (Table 1). Compound 14 was easily
converted9 into b-glucopyranosyl azide 2-sulfonic acid
sodium salt 15. This synthetic route may be a promising
source for the synthesis of 1,2-trans-glycosyl azide or gly-
cosyl amine derivatives of sugar sulfonic acids.
a
c
O
Ph
O
Ph
O
S
O
O
+
O
N3
SiMe3
BnO
BnO
S
N3
21 (54%)
22 (13%)
Me3Si
e
e
O
O
Ph
Ph
O
O
O
O
N3
BnO
BnO
NaO3S
SO3Na
N3
23 (72%)
24 (71%)
Scheme 4 Preparation of the 2-sulfonic acid sodium salt of a- and
b-D-glucopyranosyl azide derivatives 23 and 24 through the 1,2-
trans-thio-migration of the 2-O-mesyl derivative of compound 20.
Reagents and conditions: a) NaOMe, MeOH, 2 h; b) benzaldehyde di-
methyl acetal (1.5 equiv), p-TsOH (0.02 equiv), DMF, 50 °C, 2 h; c)
Bu2SnO (1.3 equiv), CsF (2equiv), toluene, reflux, 3 h; BnBr (2
equiv), DMF, 12 h; d) MsCl (1.5 equiv), pyridine, 2 h; NaN3 (10
Recently, a useful procedure was published for the con-
version of 2-(trimethylsilyl)ethyl sulfides into thioesters10
or thiols.11 The method is suitable for the cleavage of 2- equiv), DMF, 70 °C, 8 h; e) Hg(F3CCOO)2, (1.5 equiv), CH2Cl2, H2O,
6 h; Oxone® (2.5 equiv), KOAc (20 equiv), AcOH, 4 h.
(trimethylsilyl)ethyl sulfides and 1-thio-glycosides by
treatment with carboxylic acid chlorides in the presence of
silver tetrafluoroborate as a promoter to afford the corre-
sponding thioesters in high yields.
gave 3-O-benzyl ether 20 (89%). Reaction of 20 with
mesyl chloride and subsequent thio-migration promoted
by NaN3 resulted in azido 2-S-[2¢-(trimethylsilyl)ethyl]-b-
D-glucopyranoside derivative 21 in an acceptable yield
(54%), and the a-azide isomer 22 could also be isolated as
a side product in 13% yield. Both anomers were oxidized
to crystalline 2-sulfonic acids [23 (72%) and 24 (71%)].
Peracetylated D-mannose 16 was treated with 2-(trimeth-
ylsilyl)ethanethiol in the presence of BF3·Et2O and crys-
talline compound 17 was isolated in 62% yield.
Saponification of 17 resulted in free glycoside 18 (96%)
which was converted into crystalline 4,6-O-benzylidene
derivative 19 (54%). Tin-mediated selective benzylation
Synlett 2005, No. 14, 2242–2244 © Thieme Stuttgart · New York

2244
L. Lázár et al.
LETTER
OH
O
It is well known that prop-1-enyl ethers are acid-sensitive
but we did not find any data concerning the reactivity of
sugar prop-1-enyl sulfides. To study their properties we
started from allyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-
glucopyranoside12 (25). After Zemplén deacetylation
(→26) crystalline 4,6-O-benzylidene derivative 27 was
obtained. Tin-mediated regioselective benzylation result-
ed in crystalline 3-O-benzyl ether 28. The mesylated
intermediate 29 was not characterized: the chromato-
graphically homogeneous compound was treated with
NaN3, to give exclusively the a-azido-mannopyranoside
derivative 30 as the thio-migrated product. The 2-SAll
group could not be isomerized into prop-1-enyl thioether
using a rhodium-based catalyst,13 but a very fast reaction
was observed using potassium tert-butoxide–dimethyl
formamide14. The reaction was complete in only ten
minutes at 25 °C. The NMR spectra showed the presence
of the two cis/trans-geometrical isomers, which could not
be separated, but the disappearance of the allyl ether was
confirmed by the NMR spectra. The spectra also showed
the presence of a considerable amount (ca. 50%) of 2-S-
(E/Z)prop-1-enyl glycals. When the reaction was carried
out at 80 °C the only product formed was the glycal. Its
yield could be diminished by conducting the reaction at
0 °C, the ratio of prop-1-enyl ethers and glycal was nearly
O
Ph
a
O
O
HO
HO
S
S
RO
OH
OH
26
27 R = H (67%)
28 R = Bn (86%)
b
e
c
93%
O
Ph
O
Ph
O
O
O
S
O
S
BnO
BnO
OMs
58%
OR
29
33 (E/Z) R = H
34 (E/Z) R = Ms
d
c
S
73%
d
O
Ph
O
1-azide:glycal
3:1
O
BnO
e
30
13%
S
N3
O
Ph
1-azide:glycal
3:1
O
O
BnO
f
N3
31 (E/Z)
SO3Na
O
O
36%
Ph
O
BnO
N3
32
Scheme 5 Preparation of the 2-sulfonic acid sodium salt of the a-D-
mannopyranosyl azide derivative 32 by 1,2-trans-thio-migration of
allyl 29 and prop-1-enyl 1-thio-b-D-glucopyranoside derivatives 34
(E/Z). Reagents and conditions: a) benzaldehyde dimethyl acetal (1.5
equiv), p-TsOH (0.02 equiv), DMF, 50 °C, 2 h; b) Bu2SnO (1.3
3:1, but a better yield of the desired compound 31 (E/Z) equiv), CsF (2 equiv), toluene, reflux., 3 h; BnBr (2equiv), DMF, 12
h; c) MsCl (1.5 equiv), pyridine, 2 h; d) NaN3 (10 equiv), DMF,
could not be achieved. Oxidation of the mixture [glycal
and 31] did not proceed in acetic acid either with Oxone®
70 °C, 8 h; e) (CH3)3COK (1.2 equiv), DMF, 1 h, 0 °C; f)
Hg(F3CCOO)2 (1.5 equiv), CH2Cl2, H2O, 12 h; Oxone® (2.5 equiv),
or H2O2. However, treatment of compound 31 with
Hg(TFA)2 in dichloromethane and H2O (5 equiv) for 12
hours, with subsequent oxidation successfully furnished
KOAc (20 equiv), AcOH, 4 h.
sulfonic acid 32.
References
To avoid the formation of non-desired 2-S-prop-1-enyl-
(1) (a) Dwek, R. A. Chem. Rev. 1996, 96, 683. (b) Varki, A.
glycal, we changed the route of the synthesis; the allyl
Glycobiology 1993, 3, 97. (c) Carbohydrates in Chemistry
aglycone of allyl 3-O-benzyl-4,6-O-benzylidene-1-thio-
and Biology, Vol. 1-4; Ernst, B.; Hart, G. W.; Sinaÿ, P., Eds.;
b-D-glucopyranoside (28) was isomerized into prop-1-
enyl (→33 E/Z), the OH-2 of compound 33 was mesylated
to give 34 (E/Z), and treated with azide to give 31 (E/Z),
unfortunately the yield was very low.
Wiley-VCH: Weinheim, 2000.
(2) Ryan, K. J.; Acton, E. M.; Goodman, L. J. Org. Chem. 1971,
36, 2646.
(3) Nicolaou, K. C.; Ladduwahetty, L.; Randall, J. L.;
Chuholowski, A. J. Am. Chem. Soc. 1986, 108, 2466.
(4) Johnston, B. D.; Pinto, B. M. J. Org. Chem. 2000, 65, 4607.
(5) Lipták, A.; Sajtos, F.; Jánossy, L.; Gehle, D.; Szilágyi, L.
Org. Lett. 2003, 5, 3671.
(6) Sajtos, F.; Lázár, L.; Borbás, A.; Bajza, I.; Lipták, A.
Tetrahedron Lett. 2005, 46, 5191.
(7) Franks, N. E.; Montgomery, R. Carbohydr. Res. 1968, 6,
286.
(8) Glaudemans, C. P. J.; Bertolini, M. J. Methods Carbohydr.
Chem. 1980, 8, 271.
(9) Reddie, R. N. Synth. Commun. 1987, 17, 1129.
(10) Grundberg, H.; Andergran, M.; Nilsson, U. J. Tetrahedron
Lett. 1999, 40, 1811.
On the basis of our present observation, we conclude that
the 1,2-trans thio-migration in the case of thioglycosides
proceeds with very high regioselectivity. The migration of
the SR group from the anomeric position into C-2 occurs
completely and the inversion of configuration is unambig-
uous. The anomeric configuration of the newly formed
‘glycosides’ depends partly on the properties of the thio-
aglycone. In the case of bulky aglycones the stereoselec-
tivity of the newly formed glycosides is rather poor, but
our present investigations with 1-SAc, 1-SCH2CH2SiMe3,
and also with prop-1-enyl groups show that these agly-
cones trigger a high degree of inversion at the anomeric
centre. In our opinion, 1-SAc groups are the most promis-
ing substituents at the anomeric centre.
(11) Anderson, M. B.; Ranasinghe, M. G.; Palmer, J. T.; Fuchs,
P. L. J. Org. Chem. 1988, 53, 3127.
(12) Ferrier, R. J.; Furneaux, R. H. Carbohydr. Res. 1976, 52, 63.
(13) Corey, E. J.; Suggs, J. W. J. Org. Chem. 1973, 38, 3224.
(14) (a) Gigg, R.; Warren, C. D. J. Chem. Soc. C 1968, 1903.
(b) Tarbell, D. S.; Lowett, W. E. J. Am. Chem. Soc. 1956, 78,
2259. (c) Sváta, V.; Procházka, M.; Bakos, M. Coll. Czech.
Chem. Commun. 1978, 43, 2619.
Acknowledgment
The authors thank the National Research Foundation (OTKA
AT48798, OTKA T35128) for financial support.
Synlett 2005, No. 14, 2242–2244 © Thieme Stuttgart · New York