Meijer and Ellervik
The amount of unreacted donor was determined from the
NMR spectra of the reaction mixtures, with the TMS signal
from the acceptor/products serving as an internal standard.
Exp er im en ta l Section
NMR spectra were recorded at 300 or 400 MHz. 1H NMR
spectra were assigned using 2D methods (COSY, HETCOR,
long-range HETCOR). Chemical shifts are given in ppm
downfield from the signal for Me4Si, with reference to residual
CHCl3. Reactions were monitored by TLC using alumina plates
coated with silica gel 60 F254 (Merck) and visualized either
by using UV light or by charring with H3PO4 (aqueous 5% dip
solution). Preparative chromatography was performed with
Amicon silica gel (35-70 µm, 60 Å). MeCN and CH2Cl2 used
in glycosylation reactions were stirred overnight with CaH2
and distilled immediately before use. ICl and IBr are com-
mercially available as 1 M solutions in CH2Cl2. The I2 solution
was prepared as follows: molecular iodine was purified by
sublimation and dissolved in CH2Cl2 and MeCN (2:3). Due to
low solubility the concentration was about 0.2 M. Additional
purifications of reaction mixtures were performed on a Sepha-
dex LC-20 column (diameter 1.5 cm, height 1 m) using 1:1 CH2-
Cl2-MeOH as the mobile phase.
Syn th esis of 4-Meth oxyp h en yl (Meth yl(5-a ceta m id o-
4,7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-D-glycer o-R-D-ga la cto-
2-n on u lop yr a n osyl)on a t e)-(1f3)-(4-a zid o-6-O-b en zyl-4-
d eoxy-â-D-ga la ctop yr a n osyl)-(1f4)-[2,3,4-tr i-O-ben zyl-R-
L-fu copyr an osyl]-(1f3)-(2-acetam ido-6-O-ben zyl-2-deoxy-
â-D-glu cop yr a n osid e) (14). Compound 14 was synthesized
according to the representative procedure using the molar
ratios given in Table 1. Compound 14 was obtained in 43%
and 44% yields as a 66:17:17 mixture of the R and â diaster-
eomers together with lactonized product. Unfortunately the â
and lactonized products were inseparable and no characteriza-
tion (and subsequently the anomeric configuration of the
lactone product was not determined) except HRMS was
possible. The R product, however, was obtained as a pure
sample and was characterized as follows.
14-R: [R]20 ) -34.0° (c 0.72, CHCl3); 1H NMR (CDCl3) δ
D
7.15-7.40 (m, 25 H), 6.70-6.92 (m, 4 H), 5.95 (d, 1 H, J ) 7.6
Hz), 5.40-5.47 (m, 1 H), 5.30-5.34 (m, 2 H), 5.20 (d, 1 H, J )
9.7 Hz), 5.13 (d, 1 H, J ) 3.5 Hz), 4.94-5.01 (m, 1 H), 4.95,
4.63 (ABq, 1 H each, J ) 11.6 Hz), 4.87, 4.69 (ABq, 1 H each,
J ) 11.8 Hz), 4.70-4.75 (m, 2 H), 4.58 (d, 1 H, J ) 7.6 Hz),
4.45-4.53 (m, 2 H), 4.35-4.46 (m, 2 H), 4.35-4.40 (m, 1 H),
4.29 (t, 1 H, J ) 8.0 Hz), 4.25 (dd, 1 H, J ) 12.6, 2.7 Hz), 4.17
(dd, 1 H, J ) 10.7, 1.8 Hz), 3.85-4.15 (m, 7 H), 3.66-3.80 (m,
5 H), 3.77 (s, 3 H), 3.74 (s, 3 H), 3.51-3.60 (m, 4 H), 3.11 (s, 1
H), 2.70 (dd, 1 H, J ) 13.2, 4.6 Hz), 2.06-2.14 (m, 1 H), 2.10,
2.10, 2.03, 1.97, 1.90, 1.71 (s, 3 H each), 1.11 (d, 3 H, J ) 6.4
Hz); 13C NMR (CDCl3) δ 171.30, 170.91, 170.71, 170.54, 170.39,
170.23, 168.55 (C-1’’’, J C-1’’’:H-3’’’ax ) 6.9 Hz), 155.56, 151.87,
139.21, 139.15, 139.13, 139.01, 138.19, 128.96, 128.87, 128.83,
128.74, 128.61, 128.57, 128.40, 128.29, 128.22, 127.97, 127.91,
127.69, 127.66, 127.62, 119.16, 114.80, 101.82, 99.60, 98.33,
97.91, 75.32, 75.11, 74.57, 74.36, 74.28, 73.77, 73.25, 73.16,
72.95, 71.21, 70.51, 69.26, 68.77, 68.56, 68.27, 67.37, 67.17,
62.61, 60.95, 56.05, 53.52, 50.06, 38.05, 23.73, 23.63, 21.57,
P r ecip ita tion Exp er im en ts. To a solution of 26 mg of
AgOTf in 2 mL of MeCN was added 0.10 mL of ICl at
room temperature. AgCl precipitation occurred only when a
Lewis base such as pyridine or xanthate donor
1 was
added. The experiment was repeated using MeCN-CH2Cl2 (3:
2) both at room temperature and at -72 °C, with similar
results.
Titr a tion Exp er im en ts. A 1 mL amount of a 0.1 mM
solution of ICl in MeCN was titrated with a 10 mM solution
of AgOTf in MeCN. Spectroscopic data were obtained using a
Varian Cary 300 Bio UV-vis spectrophotometer.
NMR Exp er im en ts. All spectroscopic data were obtained
using a Bruker DRX300 spectrometer at 300 MHz. We chose
to plot the ICl concentration (calculated from [ICl]0 and
∆[MeCl]), which is directly proportional to the ICl2- concentra-
tion.
Figure 2a: to 0.7 mL of CD3CN in an NMR tube was added
4 µL of MeI and 0.13 mL of ICl. Figure 2b: to 0.5 mL of CD3-
CN and 12.8 mg of AgOTf in an NMR tube, protected from
light, was added 5 µL of MeI and 0.10 mL of ICl.
21.28, 21.24, 21.18, 21.11, 17.11; HRMS calcd for C82H97N5O27
-
Na (M + Na) 1606.6269, found 1606.6274.
Rep r esen ta tive P r oced u r e for th e Sia lyla tion Rea c-
tion s. To a stirred solution of 5 (50 mg, 0.122 mmol), 1 (109
mg, 0.183 mmol), and powdered activated molecular sieves (3A,
150 mg) was added CH2Cl2 (1.6 mL) and a solution of AgOTf
(94 mg, 0.367 mmol) in MeCN (2.4 mL). The reaction mixture
was cooled to -72 °C under an argon atmosphere, and a
solution of IBr (1.0 M in CH2Cl2, 0.244 mL, 0.244 mmol) was
added dropwise after 15 min. The reaction mixture was stirred
for 2 h at -72 °C, and then diisopropylamine (0.20 mL, 1.4
mmol) was added and stirring was continued for another 20
min. The reaction mixture was then filtered (SiO2, 25:1-10:1
toluene-EtOH) and concentrated under reduced pressure. The
residue was purified on Sephadex (LH-20, 1:1 CH2Cl2-MeOH)
to give 6 (96 mg, 89%, 8:1 R: â). Compound 6 was acetylated
using standard conditions; the product obtained is identical
with that reported in the literature.12
Rea ction Kin etics. The reactions were carried out as
described in the general procedures, with the following alter-
ations: the reactions were carried out in 5 mL test tubes on a
small scale (0.75 mL of solvent). The IBr solution was added
in a single portion in order to simplify the time measuerement.
The reaction was quenched by addition of a CH2Cl2-cyclohex-
ene-diisopropylamine (2:1:1) solution at -72 °C and then
immediately filtered (SiO2) and concentrated. The residue was
dissolved in CH2Cl2 and the solution was washed twice with
acidified water (H2SO4, pH 2) and once with water and then
concentrated.
14-â: HRMS calcd for C82H97N5O27Na (M + Na) 1606.6269,
found 1606.6274.
14-la cton e: HRMS calcd for C81H93N5O26Na (M + Na)
1574.6006, found 1574.6058.
Meth yl(5-a ceta m id o-4,7,8,9-tetr a -O-a cetyl-3,5-d id eoxy-
D-glycer o-â-D-ga la cto-2-n on u lop yr a n osyl)on a te Br om id e
(7). An anomeric mixture of methyl 5-acetamido-2,4,7,8,9-
penta-O-acetyl-3,5-dideoxy-D-glycero-D-galacto-2-nonulopyra-
nosonate (120 mg, 0.225 mmol) was dissolved in HOAc (2 mL);
Ac2O (1 mL) was added, followed by HBr-HOAc (2 mL, 30%
w/v). The mixture was stirred at room temperature for 1.5 h
and then lyophilized to remove solvent and excess HBr. The
yellowish residue was filtered on a Sephadex LC-20 column
(diameter 1.5 cm, height 10 cm) using acetone as the mobile
phase and then concentrated without heating to yield a
transparent oil consisting of bromide 7 and glycal 4 (3:2). Due
to the instability of bromide 7 (eliminates to glycal 4 upon
storage and handling) the mixture was used immediately in
sialylation reactions.
Ack n ow led gm en t. This work was supported by the
Swedish Natural Science Research Council and the
Knut and Alice Wallenberg Foundation. We thank Dr.
T. Ercegovic for valuable discussions.
Su p p or tin g In for m a tion Ava ila ble: NMR spectrum of
compound 14-R. This material is available free of charge via
the Internet at http://pubs.acs.org.
(34) The counterion (in this case the triflate ion) is capable of
influencing the stereochemical outcome, as shown by Crich: Crich, D.;
Cai, W.; Dai, Z. J . Org. Chem. 2000, 65, 1291.
J O0262412
7412 J . Org. Chem., Vol. 67, No. 21, 2002