P. I. Abronina et al. / Carbohydrate Research 344 (2009) 240–244
243
b-
D
-mannopyranosyl azides (6 and 7, 1,2-trans and 1,2-cis, respec-
TBAHS (51.6 mg, 0.152 mmol), NaN3 (50 mg, 0.76 mmol), and 1 M
Na2CO3 (2 mL) were added. The two-phase mixture was vigorously
stirred at 115 °C (bath) for 2 h, after which time TLC indicated com-
plete transformation of the halide. Toluene (20 mL) was then
added, the organic phase was separated and successively washed
with satd NaHCO3, H2O (ꢂ2), and brine. The combined organic ex-
tively), which have been recently characterized by NMR and X-ray
diffraction analysis.13
The obtained pure benzoylated b-
was treated with sodium methoxide in methanol to give the
known10 b-
-mannopyranosyl azide 4. The 2D NOESY spectrum
(not shown) of azide 4 contained correlations between H-1 with
H-2, H-3, and H-5, confirming its structure as the b-anomer (see
above).
D-mannopyranosyl azide 7
D
tracts were processed as described above to give
a-D-mannopyran-
osyl azide 2 (7 mg, 8%) and b- -mannopyranosyl azide 3 (62.3 mg,
D
66%), identical to those obtained in Method A.
In conclusion, we have developed a novel expedient synthesis of
b-mannopyranosyl azide. Due to its experimental simplicity and
low cost of reagents, this procedure may find wide use in labora-
tory and industrial practice.
Method C. To a solution of 2,3,4,6-tetra-O-benzoyl-a-D-manno-
pyranosyl bromide 1 (100 mg, 0.152 mmol) in EtOAc (2 mL) TBAHS
(51.6 mg, 0.152 mmol), NaN3 (50 mg, 0.76 mmol), and 1 M NaHCO3
(2 mL) were added. The two-phase mixture was vigorously stirred
at room temperature (ꢀ20 °C) for 48 h, after which time TLC indi-
cated complete transformation of the halide. EtOAc (20 mL) was
then added, the organic phase was separated and successively
washed with satd NaHCO3, H2O (ꢂ2), and brine. The combined or-
1. Experimental
1.1. General methods
ganic extracts were processed as described above to give
nopyranosyl azide 2 (6 mg, 7%) and b- -mannopyranosyl azide 3
(61.4 mg, 65%), identical to those obtained in Method A.
a-D-man-
D
The reactions were performed with the use of commercial re-
agents (Aldrich and Fluka), and anhydrous solvents were purified
according to standard procedures. 2,3,4,6-Tetra-O-benzoyl-
mannopyranosyl bromide (1) was prepared essentially as de-
scribed for 2,3,4,6-tetra-O-benzoyl-
-[1-13C]mannopyranosyl
a-D-
1.2.1. Data for 2,3,4,6-tetra-O-benzoyl-a-D-mannopyranosyl
azide (2)
a 2D5
ꢃ
+14.1 (c 1.2, CHCl3) (lit.10
½
a 2D5
+13 (c 1.0, CHCl3)); IR
ꢃ
a-D
½
bromide.18 Optical rotations were measured using a PU-07 auto-
matic polarimeter (Russia). 1H and 13C NMR spectra were recorded
on a Bruker DRX-500 spectrometer (500.13 and 125.32 MHz,
respectively) or on a Bruker AV-600 spectrometer (600.13 and
150.57 MHz, respectively) for solutions in CDCl3 or in D2O (for 4).
The 1H NMR chemical shifts are referred to the residual signal of
CHCl3 (dH 7.27) or to the external sodium 3-(trimethylsilyl)-
2,2,3,3-tetradeuteropropanoate (TSP) in D2O (dH 0.0), the 13C
NMR—to the CDCl3 signal (dC 77.0) or to the external MeOH in
D2O (dC 31.45). Assignments of the signals in the NMR spectra were
performed using 2D-spectroscopy (COSY, gHSQC, and gNOESY) and
DEPT-135 experiments. Thin-layer chromatography was carried
out on plates with Silica Gel 60 on aluminum foil (Merck). Spots
of compounds containing carbohydrates were visualized by dip-
ping a TLC plate into a solution of 85% H3PO4 in 96% EtOH (1:10,
v/v) with subsequent heating (150 °C). Column chromatography
(cmꢁ1): 2124 (N3) (lit.10 2120, 2180), 1736 (CO) (lit.10 1720–
1740); 1H NMR (500.13 MHz, CDCl3): dH 4.54 (1H, dd, J6,6 = 12.3,
0
J5,6 = 4.5, H-6), 4.63 (1H, ddd, J4,5 = 10.1, J5,6 = 2.5, J5,6 = 4.5, H-5),
4.77 (1H, dd, J5,6 = 2.5, J6,6 = 12.3, H-60), 5.63 (3H, dd, J1,2 = 2.1,
0
J2,3 = 3.3, H-2), 5.70 (1H, d, J1,2 = 1.9, H-1), 5.84 (1H, dd, J2,3 = 3.3,
J3,4 = 10.1, H-3), 6.14 (1H, t, J = 10.1, H-4), 7.26–8.14 (20H, m, Ph);
13C NMR (125.32 MHz, CDCl3): dC 62.6 (C-6), 66.4 (C-4), 69.3 (C-
2), 70.2 (C-3), 71.0 (C-5), 87.7 (C-1), 128.4, 128.5, 128.7, 129.8,
129.9 (CH, Ph), 133.2, 133.3, 133.6, 133.7 (Cquat, Ph), 165.4 (3C),
166.1 (C@O); ESIMS: found m/z 644.1 [M+Na]+. Calcd for
C34H27N3NaO9: 644.16.
1.2.2. Data for 2,3,4,6-tetra-O-benzoyl-b-D-mannopyranosyl
azide (3)
½
a 2D5
ꢃ
ꢁ98.2 (c 1.0, CHCl3) (lit.10
½
a 2D6
ꢃ
ꢁ97 (c 3.17, CHCl3)); IR
(cmꢁ1): 2128 (N3) (lit.10 2120), 1736 (CO) (lit.10 1725–1740); 1H
was performed on Silica Gel 60 (40–63 lm, Merck). IR spectra were
NMR (500.13 MHz, CDCl3): dH 4.25 (1H, ddd, H-5), 4.55 (1H, dd,
0
0
0
0
recorded on a Carl-Zeiss M-82 IR spectrometer in the 600–
3800 cmꢁ1 range for solutions in CHCl3. Mass spectra (electrospray
ionization, ESI) were recorded on a Finnigan LCQ mass spectrome-
ter for 2 ꢂ 10ꢁ5 M solutions in CH2Cl2–MeOH mixtures.
J5,6 = 4.4, J6,6 = 12.2, H-6), 4.82 (1H, dd, J5,6 = 2.6, J6,6 = 12.2, H-
60), 5.08 (1H, s, H-1), 5.63 (1H, dd, J2,3 = 2.9, J3,4 = 10.1, H-3), 5.96
(1H, d, J2,3 = 2.9, H-2), 6.07 (1H, t, J4,5 = 10.0, H-4), 7.25–8.18
(20H, m, Ph); 13C NMR (125.32 MHz, CDCl3): dC 62.5 (C-6), 66.1
(C-4), 70.0 (C-2), 71.9 (C-3), 74.7 (C-5), 85.5 (C-1), 128.3, 128.5,
1.2. 2,3,4,6-Tetra-O-benzoyl-a-D-mannopyranosyl azide (2) and
128.6, 129.8, 130.0 (CH, Ph), 133.2, 133.4, 133.56, 133.58 (Cquat
,
2,3,4,6-tetra-O-benzoyl-b- -mannopyranosyl azide (3)
D
Ph), 165.2 (2C), 165.5, 166.0 (C@O); ESIMS: found m/z 644.1
[M+Na]. Calcd for C34H27N3NaO9: 644.16.
Method A. To a solution of 2,3,4,6-tetra-O-benzoyl-a-D-manno-
pyranosyl bromide (1) (100 mg, 0.152 mmol) in benzene (2 mL),
tetrabutylammonium hydrogen sulfate (TBAHS) (51.6 mg,
0.152 mmol), NaN3 (50 mg, 0.76 mmol), and 1 M Na2CO3 (2 mL)
were added. The two-phase mixture was vigorously stirred at
85 °C (bath) for 7 h, after which time TLC indicated complete trans-
formation of the halide. Benzene (20 mL) was then added, the or-
ganic phase was separated and successively washed with satd
NaHCO3, H2O (ꢂ2), and brine. The combined organic extracts were
dried (Na2SO4), filtered, and evaporated under reduced pressure.
The resultant syrup was purified by chromatography on a silica
gel column (toluene?toluene–EtOAc, 19:1) to give 2,3,4,6-tetra-
1.3. b-
D-Mannopyranosyl azide (4)
To a solution of 2,3,4,6-tetra-O-benzoyl-b-
D
-mannopyranosyl
azide (3) (60 mg, 0.097 mmol) in MeOH (0.5 mL), 1 M solution of
MeONa in MeOH (0.5 mL) was added. The mixture was stirred at
ꢀ21 °C for 18 h, after which time TLC indicated complete transfor-
mation. The reaction mixture was neutralized with Dowex 50 ꢂ 8
(H+) ion-exchange resin. The resin was filtered and washed with
MeOH (20 mL), the combined filtrates were evaporated under re-
duced pressure. The resultant syrup was dissolved in water
(20 mL) and washed with light petroleum ether (5 ꢂ 25 mL), and
O-benzoyl-
uene–EtOAc, 19:1) and 2,3,4,6-tetra-O-benzoyl-b-
osyl azide (3) (66 mg, 70%; Rf = 0.52, toluene–EtOAc, 19:1).
Method B. To a solution of 2,3,4,6-tetra-O-benzoyl- -manno-
pyranosyl bromide (1) (100 mg, 0.152 mmol) in toluene (2 mL)
a-
D-mannopyranosyl azide (2) (5 mg, 6%; Rf = 0.67, tol-
the aqueous phase was concentrated in vacuo to give b-D-manno-
D
-mannopyran-
pyranosyl azide (4) (18.3 mg, 92%; Rf = 0.62, CHCl3–MeOH, 4:1).
½
a 2D0
ꢃ
ꢁ36.8 (c 1.0, H2O) (lit.10
½ ꢃ
a 2D3
ꢁ37 (c 0.98, H2O)); 1H NMR
a
-D
(600.13 MHz, D2O): dH 3.43–3.47 (1H, m, H-5), 3.575 (1H, t,
J3,4 = 9.7, J4,5 = 9.6, H-4), 3.626 (1H, dd, J2,3 = 3.2, J3,4 = 9.7, H-3),