Efficient O-glycosylation of diethyl oxoglutarate via 1,2-O-sulfinyl derivatives

Article abstract of DOI:10.1016/j.tetlet.2007.05.083

1,2-O-Sulfinyl derivatives of d- and l-arabinose, d-xylose and d-glucose treated by potassium anion of diethyl oxoglutarate gave, exclusively, the corresponding O-glycosides in 92-97% yields.

Full text of DOI:10.1016/j.tetlet.2007.05.083

Tetrahedron Letters 48 (2007) 5087–5089
Efficient O-glycosylation of diethyl oxoglutarate via
1,2-O-sulfinyl derivatives
a
b
a
a,
*
`
Abdelhafid Benksim, Mohamed Massoui, Daniel Beaupere and Anne Wadouachi
aLaboratoire des Glucides UMR 6219 CNRS, Universite´ de Picardie Jules Verne, 33 Rue Saint-Leu, F-80039 Amiens, France
bLaboratoire de Chimie des Agroressources, Faculte´ des Sciences, Universite´ Ibn Tofaı¨l, Ke´nitra, Morocco
Received 28 February 2007; revised 4 May 2007; accepted 15 May 2007
Available online 18 May 2007
Abstract—1,2-O-Sulfinyl derivatives of D- and L-arabinose, D-xylose and D-glucose treated by potassium anion of diethyl oxoglu-
tarate gave, exclusively, the corresponding O-glycosides in 92–97% yields.
Ó 2007 Elsevier Ltd. All rights reserved.
Efficient glycosylation methods are of particular interest
in the synthesis of biologically important glycomole-
cules.1 A number of glycosyl donors have been described
as significant alternatives to glycosyl bromides and
chlorides classically used, such as thioglycosides, tri-
chloroacetimidates, glycosyl fluorides and iodides,
N-pentenylglycosides, DISAL glycosides.2 The forma-
tion of the glycosidic bond is often subject to competing
SN1 and SN2 processes. The advantage of SN2 displace-
ment reactions is their potential for stereospecificity.
Nucleophilic opening of the cyclic sulfite derivatives is
regio- and stereospecific at the anomeric centre.
fungal, antibacterial and immunosuppressive properties,
was prepared from 2-geranyl-dimethyl-3-oxoglutarate
(Fig. 1).9
1,2-O-Sulfinyl-glycofuranoses and pyranoses 4a–d were
treated with enolate anion formed in situ from diethyl
3-oxoglutarate 1 (Fig. 2 and Table 2).
O
OH
O
CO2Me
O
CO2Me
In the previous work, we have shown that 1,2-O-sulfinyl
monosaccharide derivatives are useful precursors for
stereoselective N-glycosylation reactions to form
glycosyl azides and 1,2-cyclic carbamates3,4 for O-gly-
cosylations aimed at obtaining aryl-glycosides5 and C-
glycosylation towards the syntheses of cyanoglycosides.6
HO2C
MeO
mycophenolic acid
Figure 1.
O
O
O
Given our past successes with these substrates we be-
came interested in studying their reactivity towards the
enolate anion derived from diethyl 3-oxoglutarate. Di-
alkyl 3-oxoglutarates have been studied in metal com-
plexation reactions and their alkylation.7 They have also
been used as starting materials for syntheses of phenolic
derivatives.8 For example, mycophenolic acid, which
possesses many biological activities including anti-
B-M+
Solvent
O
O
O
O
O
O
O-M+
1
2
O
O
S
4a-d
EtO
O
O
O
O
O
O
Keywords: Cyclic sulfite; Carbohydrates, Monosaccharides; Nucleo-
phile substitution; Stereospecific glycosylation.
5a-d
OEt
OH
*
Corresponding author. Tel.: +33 3 22 82 75 27; fax: +33 3 22 82 75
60; e-mail: anne.wadouachi@u-picardie.fr
Figure 2.
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.05.083

5088
A. Benksim et al. / Tetrahedron Letters 48 (2007) 5087–5089
3,4-O-Isopropylidene-D- and L-arabinopyranoses 3a
and 3b were selectively synthesized from D- and L-arabi-
noses, respectively, by treatment with 2,2-dimethoxy-
propane in dry DMF in the presence of catalytic p-
TsOH (Table 2).11
with potassium anion (40 min) (Table 1, entry 2); either
DMF and THF gave only O-glycoside compound 5a.
THF was found to be less effective for promoting
nucleophilic displacement. The use of DMF
enhanced the reaction yield (95%) compared with THF
(69%).
3,5-Di-O-benzyl-D-xylofuranose 3c was prepared from
diisopropylidene-D-xylofuranose in three steps in 57%
overall yield.12 Diisopropylidene D-glucopryranose
afforded 3,4,6-tri-O-benzyl-D-glucofuranose 3d in four
steps from D-glucose in 36% overall yield (Table 2).12
Compounds 4b–d were treated with the potassium
form of the diethyl-3-oxoglutarate anion of 1 previously
prepared in DMF with potassium carbonate, to give
3-(glycosyloxy)-pent-2-ene dioic acid diethyl ester 5b–d
in 92–97% yields (Table 2).10
Sulfinylation of 1,2-diols 3a–d was realized with N,N0-
thionyldiimidazole and gave the corresponding cis 1,2-
O-sulfinyl substrates 4a–d in 83–97% yields.3,6 The gly-
cosylation reaction was first studied with 1,2-O-sulfi-
nyl-D-arabinopyranose 4a6 (Table 1).
Compounds 5a–d were characterized by NMR spectro-
scopy. Anomeric protons appeared between d 4.88 and
5.51 ppm and coupling constants J1,2 between 6.8 and
7.1 Hz for pyranose sugars and J1,2 = 0 Hz for furanose
derivatives, both of which indicated the 1,2-trans config-
1
The yields obtained by using potassium or sodium car-
bonate were equivalent.10 The reaction time was shorter
uration (Table 2). The H data were in agreement with
the literature, for 1,2-trans O-phenyl-a-L-arabinofurano-
side, the H-1 signal appeared as a singlet at d 5.7 ppm.13
13C NMR spectra showed the signal of anomeric carbon
at d 100.4 ppm for D- and L-arabinopyranosides com-
pounds 5a and 5b. For furanic derivatives 5c and 5d d
of C-1 were between d 106.2 and 106.4 ppm, which
agreed with our previous work: 1,2-trans phenyl O-gly-
copyranosides had similar data.14 Two signals appeared
Table 1. Optimization of the reaction of 4a with anion of 1
Entry Solvent Base (2 equiv) Reaction time Yield % 5a
1
2
3
DMF
DMF
THF
Na2CO3
K2CO3
K2CO3
1 h
40 min
1 h
93
95
69
Table 2. Synthesis of diethyl oxoglutarate O-glycosides derivatives
Starting material
Cyclic sulfite
% Yield Product
Reaction
time
%
d Anomeric J1,2
d Anomeric
Yield proton (Hz) carbon
O
O
O
O
OH
O
O
O
S
82
50 min
95
4.91
7.10 100.4
O
O
O
OH
O
O
4a
3a
O
O
O
O
O
OH
5a
O
O
O
O
O
OH
O
O
S
O
88
1 h
97
4.88
6.86 100.4
O
O
O
O
O
OH
O
O
4b
3b
O
OH
5b
O
O
O
O
O
O
OH
OH
O
BnO
BnO
97
30 min
94
5.50
0
106.4
O
S
O
O
BnO
BnO
O
BnO
O
3c
4c
BnO
OH
5c
O
O
O
O
O
BnO
BnO
OH
OH
O
BnO
BnO
BnO
O
96
40 min
92
5.51
0
106.2
S
BnO
O
O
BnO
O
BnO
O
3d
4d
BnO
OH
5d

A. Benksim et al. / Tetrahedron Letters 48 (2007) 5087–5089
5089
Table 3. 13C NMR data of diethyl 3-oxoglutarate moiety of 5a–d
Chem. Rev. 1993, 93, 1503–1531; (c) Pellissier, H. Tetra-
hedron 2005, 61, 2947–2993; (d) Toshima, K. Carbohydr.
Res. 2006, 341, 1282–1287.
Products
C-10
C-20
C-30
C-40
C-50
5a
5b
5c
5d
170.0
170.0
170.1
169.9
98.7
98.7
97.7
97.5
165.3
165.3
165.0
165.1
37.7
37.7
38.6
38.7
167.2
167.2
167.8
167.8
2. (a) Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 98,
213–236; (b) Sinay, P. Pure Appl. Chem. 1991, 63, 519–
¨
528; (c) Toshima, K. Carbohydr. Res. 2000, 327, 15–26; (d)
Jensen, K. J. J. Chem. Soc., Perkin Trans. 1 2002, 2219–
2233; (e) Jacobsson, M.; Malmberg, J.; Ellervik, U.
Carbohydr. Res. 2006, 341, 1266–1281.
between d 169.9–170.1 ppm and d 167.2–167.8 ppm
3. El Meslouti, A.; Beaupere, D.; Demailly, G.; Uzan, R.
Tetrahedron Lett. 1994, 35, 3913–3916.
4. (a) Beaupere, D.; El Meslouti, A.; Lelievre, P.; Uzan, R.
Tetrahedron Lett. 1995, 36, 5347–5348; (b) Roussel, F.;
Wadouachi, A.; Beaupere, D. Carbohydr. Lett. 2000, 3,
397–404.
assigned to the carbonyl groups C-50 and C-10, respec-
tively, quaternary C-30 had
a signal between d
165.0 and 165.3 and methylene C-40 between d 37.7
and 38.7 ppm (Table 3). These data agreed with that
reported in the literature for O-alkylated 3-
oxoglutarates.15
5. Aouad, M. E.; El Meslouti, A.; Uzan, R.; Beaupere, D.
Tetrahedron Lett. 1994, 35, 6279–6282.
6. Benksim, A.; Beaupere, D.; Wadouachi, A. Org. Lett.
2004, 6, 3913–3915.
We have observed that reactions of cyclic sulfites with
alcohols did not produce the desired O-glycosides. Alk-
oxides led to hydrolysis of the sulfite via addition at the
sulfur atom and gave starting material. D-Glucopyrano-
side compounds have already been prepared from 1,2-O-
sulfinyl derivatives by reaction with allyl, benzyl and
cyclohexyl alcohol in the presence of lanthanide (III) tri-
flates. Tri-acetylated or benzoylated protected 1,2-cyclic
sulfite of D-glucose provided an a/b mixture of ano-
7. (a) Hay, R. W.; Caughley, B. P. Aust. J. Chem. 1967, 20,
1829–1839; (b) Muramoto, Y.; Oishi, K.; Ichimoto, I.;
Ueda, H. Nippon Nogei Kagaku Kaishi 1974, 48, 507–513.
8. Covarrubias-Zuniga, A.; Rios-Barrios, E. J. Org. Chem.
1997, 62, 5688–5689.
9. (a) Covarrubias-Zuniga, A.; Gonzalez-Lucas, A. Tetrahe-
dron Lett. 1998, 39, 2881–2882; (b) Covarrubias-Zuniga,
A.; Gonzalez-Lucas, A.; Dominguez, M. M. Tetrahedron
2003, 59, 1989–1994.
10. Typical procedure of O-glycosylation of diethyl oxoglutar-
ate. To a solution of diethyl oxoglutarate (2 equiv) and
anhydrous potassium carbonate (2.05 equiv) in anhydrous
DMF previously stirred for 1 h, was added dropwise a
solution of 1,2-O-sulfinyl-glycose derivative (1 equiv) in
anhydrous DMF. The mixture was heated at 70 °C until
disappearance of the cyclic sulfite, as checked by thin layer
chromatography (hexane–EtOAc 1:1). Then after addition
of methanol, the solvents were evaporated under reduced
pressure and the residue extracted with CH2Cl2–H2O
(70:30). The organic layers were dried on Na2SO4 then
concentrated. The flash chromatography of the residue
afforded the corresponding O-glycoside derivatives.
11. Kiso, M.; Hasegawa, A. Carbohydr. Res. 1976, 52, 95–101.
12. Du, Y.; Kong, F. J. Carbohydr. Chem. 1996, 15, 797–
819.
mers, and only benzyl-protected sulfite gave
b
stereospecificity.16
As we observed with our previous results, reactions
proceeded efficiently with the stabilized anions such as
phenolate; the mechanism of the reaction was an
SN2 displacement at the anomeric atom and only gave
1,2-trans compounds.3–6
In the case of diethyl 3-oxoglutarate, the corresponding
stabilized enolate led only to the O-glycosides com-
pounds without hydrolysis reaction.
In summary, we have described an easy access to O-gly-
cosides derived from diethyl 3-oxoglutarate in good
yields, with free 2-hydroxyl. This method is suitable
for the synthesis of complex glycosides in which the C-
2 position is glycosylated.17 The affinity of complexation
of these glycosides is evaluated with uric acid and will be
reported in due course.
13. Sadeh, S.; Zehavi, U. Carbohydr. Res. 1982, 101, 152–
154.
`
14. Joubert, P.; Beaupere, D.; Wadouachi, A.; Chateau, S.;
´
Sangwan, R. S.; Sangwan-Norreel, B. S. J. Nat. Prod.
2004, 67, 348–351.
15. Covarrubias-Zuniga, A.; German-Sanchez, L. S.; Avila-
Zarraga, J. G. Synth. Commun. 2003, 33, 3165–3172.
16. Sanders, W. J.; Kiessling, L. L. Tetrahedron Lett. 1994, 35,
7335–7338.
References and notes
17. Dushin, R. G.; Danishefsky, S. J. J. Am. Chem. Soc. 1992,
114, 3471–3475.
1. For reviews see: (a) Brown, L.; Thomas, R. Aust. J.
Pharm. Sci. 1979, 8, 1–10; (b) Toshima, K.; Tatsuka, K.