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Can. J. Chem. Vol. 88, 2010
acetonitrile (20 mL), 1c (330 mg, 1.04 mmol, 5.8 equiv.)
was added and stirred until all the galactopyranosyl bromide
had reacted (2–3 days, TLC monitored, ethyl acetate:hexane,
2:3, Rf = 0.13). A clear colorless oil (389 mg, 0.644 mmol,
66% yield) was isolated after purification by column chro-
matography (silica gel, ethyl acetate:hexane, 1:3). UV
(MeOH, RT) lmax (3): 229 nm (5.10 mmol/L–1 cm–1). FTIR
n (cm–1): 3411 (wbr), 2980 (w), 2930 (w), 2850 (w), 1752
(s), 1513 (w), 1458 (w), 1438 (w), 1370 (m), 1224 (sbr),
1171 (w), 1137 (w), 1081 (m), 1063 (m), 1010 (w), 950
(w), 914 (w), 902 (w), 868 (w), 840 (w), 780 (w), 766 (w),
750 (w), 721 (w), 603 (w), 496 (w), 410 (w). 1H NMR
(400 MHz, CD3OD) d: 5.40 (m, 3H, overlapped, H-1, H-2,
and H-4), 5.23 (dt, 1H, J = 7.2, 2.6 Hz, H-3), 4.18 (m, 3H,
overlapped, H-5, H-6, and H-7), 4.01 (m, 2H, H-1@ and H-
5@), 2.95 (m, 3H, overlapped, H-1’, H-3’, and H-5’), 2.15 (s,
3H, CH3), 2.03 (s, 3H, CH3), 2.02 (s, 3H, CH3), 1.96 (s, 3H,
CH3), 1.82 (m, 2H, H-2’ and H-4’), 1.60 (m, 2H, methylene
Hs), 1.43 (s, 9H, t-butyl H), 1.38 (m, 2H, partly overlapped
by t-butyl peak, H-2@ and H-4@). 13C NMR (75 MHz,
CD3OD) d: 170.81 (C=O), 170.70 (C=O), 170.18 (C=O),
169.78 (C=O), 157.46 (Boc’s C=O), 100.81 (C-1), 78.79
(Boc’s tertiary carbon), 71.42 (C-5), 71.20 (C-3), 67.32 (C-
2), 67.22 (C-4), 61.26 (C-6), 50.91, 50.74 (C1’ and C-5’),
45.03 (4-aminomethyl carbon), 35.84 (C-3’), 28.11, 28.05
(C-2’ and C-4’), 27.58 (Boc CH3), 19.38, 19.30 (acetyl
CH3). MS (ESI) m/z: 627.2 [M + Na]+, 1230.7 [2M + Na]+.
MS/MS (ESI) m/z: 627.3 [M + Na]+, 583.0 [M + Na –
CO2]+, 567.5, 522.9, 441.5, 365.7, 217.9. HR-MS (ESI)
calcd. for NaC25H40N4O13 [M + Na]+: 627.2490. Found:
627.2474. DSC onset temperature at 192.6 8C, decomposi-
tion temperature at 220.2 8C, DH = +62.0 kJ mol–1. Anal.
calcd. for C25H40N4O13: C, 49.66; H, 6.67; N, 9.27. Found:
C, 49.98; H, 6.54; N, 9.06.
very high. UV (MeOH, RT) lmax (3): 230 nm (3.86 mmol/
L–1 cm–1). FTIR n (cm–1): 3431 (mbr), 2960 (w), 2926 (w),
2860 (w), 1752 (s), 1681 (s), 1508 (w), 1432 (w), 1384 (m),
1373 (m), 1232 (sbr), 1182 (m), 1134 (m), 1080 (m), 1062
(s), 992 (w), 955 (w), 915 (w), 837 (m), 801 (m), 780 (w),
1
723 (m), 601 (w), 519 (w), 495 (w), 462 (w), 409 (w). H
NMR (400 MHz, CD3OD) d: 5.40 (m, 3H, overlapped, H-1,
H-2, and H-4), 5.23 (dt, 1H, J = 7.2, 2.6 Hz, H-3), 4.12 (m,
3H, overlapped, H-5, H-6, and H-7), 4.06 (m, 2H, H-1@ and
H-5@), 3.00 (dd, 2H, J = 22.4, 10 Hz, H-1’ and H-5’), 2.88 (t,
1H, J = 6.8 Hz, H-3’), 2.15 (s, 3H, CH3), 2.03 (s, 3H, CH3),
2.02 (s, 3H, CH3), 1.95 (s, 3H, CH3), 1.90 (m, 2H, H-2’ and
H-4’), 1.81 (m, 2H, methylene Hs), 1.49 (m, 2H, H-2@ and
H-4@). 13C NMR (75 MHz, CD3OD) d: 170.80 (C=O),
170.63 (C=O), 170.14 (C=O), 169.83 (C=O), 100.78 (C-1),
71.47 (C-5), 71.13 (C-3), 67.29 (C-2), 67.19 (C-4), 61.21
(C-6), 53.63 (DCM solvent), 50.36, 50.17 (C1’ and C-5’),
43.86 (4-aminomethyl carbon), 33.61 (C-3’), 27.58, 27.48
(C-2’ and C-4’), 19.37, 19.28 (acetyl CH3). MS (ESI) m/z:
527.1 [M + Na]+, 505.0 [M + H]+, 1008.8 [2M + H]+,
1030.7 [2M + Na]+. MS/MS (ESI) m/z: 505.0 [M + H]+,
390.8 [M – 4-aminomethylpiperidine (NC5H9–CH2NH2)]+.
MS/MS (ESI) m/z: 527.0 [M + Na]+, 399.9 [M + Na – 4-
aminomethylpiperidine (NC5H9–CH2NH2)
–
nitrogen]+,
371.0, 353.0, 341.1, 310.9, 295.0. HR-MS (ESI) calcd. for
C20H33N4O11 [M + H]+: 505.2146. Found: 505.2134. DSC
onset temperature at 150.4 8C, decomposition temperature
at 174.5 8C, DH = +52.5 kJ mol–1.
O2-(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl) 1-(4-
[1,2,3,4-tetra-O-acetyl-b-D-glucopyranosyl]-4-
aminomethylpiperidin-1-yl)diazen-1-ium-1,2-diolate (2e)
To a solution of 2d (310 mg, 0.615 mmol, 1 equiv.) in
anhydrous acetonitrile (20 mL), Na2CO3 (80.0 mg,
0.755 mmol, 1.2 equiv.) was added followed by a solution
of GluDSC (345 mg, 0.705 mmol, 1.15 equiv.) in anhydrous
acetonitrile (10 mL). The solution was stirred under N2 at
RT overnight. The solution was passed through a fine frit
filter, and the solvent was removed in vacuo. The residue
was dissolved in dichloromethane (DCM, 10 mL). This or-
ganic layer was washed thrice with distilled water (15 mL/
wash), dried over Na2SO4 (2 g), filtered, and its solvent re-
moved in vacuo. TLC demonstrated the appearance of a sin-
gle new spot (ethyl acetate:hexane, 7:3, with Rf = 0.34).
Interestingly, over time, two new spots appeared on the
TLC plate above the initial new spot (Rf = 0.66, 0.76).
NMR and MS studies however show that the TLC spot with
Rf = 0.34 corresponds to the desired compound. The isolated
material was purified by column chromatography (silica gel,
ethyl acetate:hexane, 7:3) to yield a clear, colorless oil
(427 mg, 0.486 mmol, 79%). UV (MeOH, RT) lmax (3):
229 nm (4.33 mmol/L–1 cm–1). FTIR n (cm–1): 3391 (wbr),
2942 (w), 2872 (w), 1756 (s), 1652 (w), 1520 (w), 1436
(w), 1371 (m), 1221 (sbr), 1153 (w), 1079 (m), 1039 (m),
952 (w), 912 (w), 902 (w), 847 (w), 775 (w), 743 (w), 702
O2-(2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl) 1-(4-
aminomethylpiperidin-1-yl)diazen-1-ium-1,2-diolate (2d)
A solution of compound 2c (389 mg, 0.644 mmol, 1
equiv.) in distilled dichloromethane (DCM, 20.0 mL), and
trifluoroacetic acid (TFA, 10.0 mL) was prepared initially
at around 0 8C and then stirred under N2 at RT for 2–3 h.
NMR studies in deuterated DCM/TFA solutions demon-
strated the complete absence of the Boc methyl peak after
this time period with near 100% conversion. Prolonged ex-
posure of this product under such acidic conditions, how-
ever, led to deterioration of the product. The acid was
subsequently removed from solution via a vacuum line with
successive dilutions using DCM (100 mL). The residue was
dissolved with aqueous NaCO3 (1.0 mol/L solution) and ex-
tracted thrice with DCM (30 mL/extraction). The combined
extracts were dried over Na2SO4 (2 g), filtered, and the sol-
vent removed using a vacuum line to yield a sticky yellow
oil (310 mg). The product turned out to be reactive with
silica gel, and hence was not further purified by column
chromatography. The yield for the ensuing intermediate of
this product (see synthesis of protected (2e)) was 79% as-
suming the 310 mg isolated in this synthesis is essentially
compound 2d. On the other hand, during another trial of
these syntheses, compound 2e was isolated with an 81%
yield relative to 2c. This result suggests that the yield of
compound 2d obtained between these two synthetic steps is
1
(w), 647 (w), 601 (w), 558 (w), 496 (w), 410 (w). H NMR
(400 MHz, CD3OD) d: 5.82 (d, 1H, J = 8.4 Hz, glucopyra-
nosyl H-1), 5.40 (m, 3H, overlapped, H-1, H-2, and H-4),
5.33 (t, 1H, J = 9.6 Hz, glucopyranosyl H-3), 5.23 (dt 1H, J =
6.8, 2.4 Hz, galactopyranosyl H-3), 5.06 (t, 1H, J = 9.8 Hz,
dd overlapping, 1H, J = 29.2, 9.6 Hz, glucopyranosyl H-2
Published by NRC Research Press