1502
D. Gueyrard et al.
PAPER
1) MeONa
THF–MeOH
(1:1)
OBn
All reactions were conducted under argon atmosphere. All common
reagents were used as obtained from commercial suppliers without
further purification. Tetrahydrofuran was distilled over Na/Ben-
zophenone. Flash column chromatography was carried out with sil-
ica gel (36–63 mesh). Specific optical rotations were measured with
a Perkin Elmer (model 141) polarimeter using a 10-cm cell. NMR
spectra were recorded on a Bruker Avance DRX 300 spectrometer
in CDCl3 using tetramethylsilane as internal standard. MS data were
recorded on a ThermoFinnigan MAT 95 XL spectrometer. IR spec-
tra were recorded on a Perkin Elmer FT apparatus.
OBn
O
O
BnO
BnO
BnO
BnO
SO2CH3
SO2Btz
2) Mel
BnO
BnO
5
8a
81%
Scheme 4 Ipso substitution
1) MeONa
THF–MeOH
(1:1)
OBn
O
OBn
O
Anomeric Vinyl Sulfone Synthesis; General Procedure
In a 50 mL round-bottomed flask under argon, 2,3,4,6-tetra-O-ben-
zyl-D-gluconolactone (1.137 g, 2.11 mmol) and 2-methanesulfonyl-
benzothiazole (540 mg, 1.2 equiv) were dissolved in freshly
distilled THF (10 mL) at –78 °C. Then a 1 M solution of LiHMDS
in THF (5.072 mL, 2.4 equiv) was added dropwise over 10 min.
Stirring was maintained during 30 min and then, the reaction mix-
ture was quenched by addition of AcOH (0.362 mL, 3 equiv). After
hydrolysis, the mixture was extracted with EtOAc (2 ×), dried over
Na2SO4 and evaporated. The residue was dissolved in anhydrous
THF (10 mL), and TFAA (1.655 mL, 8 equiv) and pyridine (2.421
mL, 20 equiv) were added dropwise. Stirring was maintained for 16
h at r.t. and then the reaction was hydrolyzed with a sat. solution of
NaHCO3 (10 mL). The mixture was extracted with EtOAc (2 ×),
dried over Na2SO4, concentrated by rotary evaporation and purified
by flash chromatography to afford the desired product (yield:
1.022 g, 66%).
BnO
BnO
BnO
SO2Btz
BnO
SO2R
2) RX
BnO
BnO
5
8
Scheme 5 Screening of the electrophilic partner
In summary, we have demonstrated an access to activated
glycals. This coupling–dehydratation sequence leads to
anomeric vinyl sulfones. These molecules can be subse-
quently transformed into a new class of C-glycoside endo-
glycals through transsulfonylation process.
We are currently investigating the use of the anomeric sul-
fone group as phosphate mimic14 to design new potential
inhibitors of glycogen phosphorylase and glucosyltrans-
ferase.
Table 7 13C NMR Data for Compounds 8a–h (d)
Com- C-1
pound
C-2
C-3
C-4
C-5
C-6
CH2
54.8
OCH2Ph
OCH2Ph
R
8a
8b
8c
8d
8e
8f
136.7 136.1 73.4
137.0 136.5 73.8
137.3 136.7 74.0
136.6 136.5 73.6
136.8 136.3 73.6
136.9 136.2 73.6
137.0 136.2 73.7
136.3 136.2 73.3
73.2
76.7
68.2
128.2, 128.3, 128.4, 128.5, 71.4, 72.6, 73.7, 42.5
128.6, 128.8, 128.9, 129.0, 74.8
137.4, 137.9, 138.1, 138.2
73.3
73.5
73.3
73.2
73.2
73.2
73.3
76.9
77.1
76.8
76.8
76.8
76.8
76.6
68.3
68.5
68.2
68.2
68.3
68.3
68.3
51.1
50.8
53.2
53.4
52.8
52.9
53.7
128.2, 128.3, 128.4, 128.5, 71.2, 72.7, 73.8, 58.8, 125.4,
128.7, 128.8, 128.9, 129.0, 75.0
137.4, 138.0, 138.2
125.5
128.2, 128.3, 128.4, 128.5, 71.2, 72.8, 73.8, 60.6, 128.0,
128.7, 128.8, 128.9, 129.0, 75.0
137.3, 138.0, 138.1, 138.2
129.2, 131.6
128.2, 128.3, 128.4, 128.5, 71.3, 72.6, 73.7, 53.4, 58.3, 164.1
128.6, 128.8, 128.9, 129.0, 74.9
137.3, 137.9, 138.1, 138.2
128.2, 128.3, 128.4, 128.5, 71.3, 72.7, 73.8, 26.6,53.2, 117.3,
128.7, 128.8, 128.9, 129.0, 74.8
137.4, 138.0, 138.1, 138.2
134.7
128.1, 128.3, 128.4, 128.5, 71.3, 72.6, 73.7, 22.3, 28.4, 28.7,
128.7, 128.8, 128.9, 129.0, 74.9
137.5, 138.0, 138.1, 138.3
28.8, 29.3, 33.1,
34.3, 54.2
8g
8h
128.2, 128.3, 128.4, 128.5, 71.3, 72.7, 73.7, 14.2, 22.0, 22.6,
128.7, 128.8, 128.9, 129.0, 74.9
137.5, 138.0, 138.1, 138.3
30.9, 54.3
128.3, 128.4, 128.5, 128.6, 71.4, 72.4, 73.8, 60.9, 129.2,
128.8, 128.9, 129.0, 129.1, 75.1
137.3, 137.9, 138.1, 138.3
134.4, 136.8,
189.7
Synthesis 2006, No. 9, 1499–1503 © Thieme Stuttgart · New York