The Journal of Organic Chemistry
Article
Hz, 1H), 3.64 (d, J = 5.20 Hz, 1H), 3.63 (d, J = 2.43 Hz, 1H), 3.62−
3.60 (m, 1H), 3.59 (dd, J = 4.87, 2.14 Hz, 1H), 3.49−3.45 (m, 1H),
3.34 (ddd, J = 10.06, 2H); 13C NMR (125 MHz, D2O): δ (ppm) 94.8,
90.5, 76.7, 73.8, 71.7, 70.9, 70.7, 70.4, 61.4, 61.2, 57.7, 55.1; HRMS-
FAB: [M − H] calcd for C8H11F3NO6− 274.0544; found: 274.0541.
2-Deoxy-2-[(trifluoroacetyl)amino]-D-glucopyranose-1,3,4,6-
tetraacetate (20). Pyridine (56.3 mL) and Ac2O (32.5 mL) were
added to 19 (5.26 g, 19.2 mmol). The reaction mixture was stirred for
3 h at room temperature. The solution was concentrated in vacuo and
coevaporated with toluene (10 mL) three times. The resulting residue
was recrystallized in Et2O (15 mL) and petroleum ether (5 mL) to
17.14, 10.20 Hz, 1H), 6.04 (dd, J = 17.14, 1.35 Hz, 1H), 5.60 (dd, J =
10.23, 1.34 Hz, 1H), 5.28 (dd, J = 6.63, 3.26 Hz, 1H), 3.88−3.83 (m,
1H), 3.68 (dd, J = 6.66, 3.67 Hz, 1H), 3.65−3.62 (m, 3H), 3.59 (m,
1H); 13C NMR (125 MHz, D2O): δ (ppm) 165.8, 129.4, 128.0, 93.5,
72.6, 70.4, 69.4, 60.1, 53.7; HRMS-FAB: [M − H] calcd for
C9H15NO9P− 312.0490; found: 312.0486.
P′-[2-(Acetylamino)-2-deoxy-α-D-glucopyranosyl] Ester Uri-
dine 5′-(Trihydrogen diphosphate), (UDP-GlcNAc, 27). 1H
NMR (500 MHz, D2O): δ (ppm) 7.87 (dd, J = 8.08, 2.41 Hz, 1H),
5.93−5.86 (m, 2H), 5.44 (d, J = 3.28 Hz, 1H), 4.32−4.25 (m, 2H),
4.24−4.08 (m, 3H), 3.94−3.88 (m, 1H), 3.86 (ddd, J = 8.03, 5.20, 2.66
Hz, 1H), 3.80 (dd, J = 17.63, 9.17 Hz, 1H), 3.73 (ddd, J = 18.49, 9.53,
5.39 Hz, 2H), 3.47 (ddd, J = 9.52, 5.51, 3.38 Hz, 1H), 2.02−1.95 (s,
3H); 13C NMR (125 MHz, D2O): δ (ppm) 174.7, 166.7, 152.1, 141.4,
102.6, 94.3, 88.4, 83.0, 73.7, 72.9, 70.8, 69.5, 69.4, 64.9, 60.2, 53.5,
22.0; HRMS-FAB: [M − H] calcd for C17H26N3O17P2− 606.0743;
found: 606.0734.
1
afford peracetylated 20 (α:β = 1:0.33, 8.51 g, 19.2 mmol, quant). H
NMR (500 MHz, CDCl3): δ (ppm) 6.60 (d, J = 9.28 Hz, 1H), 6.51 (d,
J = 8.50 Hz, 1H), 6.27 (d, J = 3.66 Hz, 1H), 5.76 (d, J = 8.71 Hz, 1H),
5.35−5.28 (m, 1H), 5.25 (t, J = 9.74, 1H), 5.22−5.16 (m, 1H), 4.45
(ddd, J = 10.84, 8.69, 3.66 Hz, 1H), 4.33−4.27 (m, 2H), 4.15 (dd, J =
12.56, 2.28 Hz, 1H), 4.09 (dd, J = 12.50, 2.33 Hz, 1H), 4.04 (ddd, J =
9.95, 3.97, 2.32 Hz, 1H), 3.85 (ddd, J = 9.50, 4.50, 2.18 Hz, 1H), 2.23
(s, 3H), 2.13 (s, 6H), 2.11 (s, 6H), 2.08 (s, 3H), 2.08 (s, 3H), 2.07 (s,
3H), 2.06 (s, 3H); 13C NMR (500 MHz, CDCl3): δ (ppm) 171.7,
170.7, 169.2, 168.6, 157.5, 157.2, 116.5, 114.2, 91.7, 89.6, 72.8, 71.9,
70.1, 69.7, 67.9, 67.2, 61.6, 61.3, 53.1, 51.7; HRMS-FAB: [M − H]
P′-[2-(1-Oxo-2-propyn-1-yl)amino-2-deoxy-α-D-glucopyra-
nosyl] Ester Uridine 5′-(Trihydrogen diphosphate) (UDP-GlcN-
1
alkyne, 28). White fluffy powder; H NMR (600 MHz, D2O): δ
(ppm) 7.89 (d, J = 8.1 Hz, 1 H), 5.89 (d, J = 4.6 Hz, 1 H), 5.88 (d, J =
8.9 Hz, 1 H), 5.47 (dd, J = 3.2, 6.9 Hz, 1 H), 4.28 (m, 2 H), 4.20 (m, 1
H), 4.18−4.16 (m, 1 H), 4.12−4.09 (m, 1 H), 3.99 (dt, J = 3.1, 10.5
Hz, 1 H), 3.87−8.83 (m, 1 H), 3.79−3.77 (m, 1 H), 3.76−3.70 (m, 2
H), 3.49−3.44 (m, 2 H); 13C NMR (150 MHz, D2O): δ (ppm) 166.2,
154.8, 151.8, 141.6, 102.6, 94.1, 88.4, 88.3, 83.2, 73.8, 72.0, 69.6, 68.3,
67.4, 64.9, 60.2, 50.3, 50.2; HRMS-FAB: [M] calcd for
−
calcd for C16H19F3NO10 442.0967; found: 442.0961.
2-Deoxy-2-[(trifluoroacetyl)amino]-D-glucopyranose-3,4,6-
1
triacetate-1-(dihydrogen phosphate) (21). H NMR (500 MHz,
D2O): δ (ppm) 5.70−5.55 (m, 1H), 5.43 (s, 1H), 5.14 (s, 1H), 4.36
(s, 2H), 4.24−4.09 (m, 1H), 3.34 (d, J = 19.11 Hz, 1H), 2.08 (s, 3H),
2.01 (s, 3H), 1.94 (s, 3H); 13C NMR (125 MHz, D2O): δ (ppm)
171.3, 170.4, 169.8, 157.2, 114.7, 92.7, 71.2, 68.2, 68.1, 61.4, 52.8;
HRMS-FAB: [M − H] calcd for C14H18F3NO12P− 480.0524; found:
480.0524.
+
C18H25N3O17P2 617.0659; found: 617.0656.
P′-[2-Deoxy-2-[(2,2,2-trifluoroacetyl)amino]-α-D-glucopyra-
nosyl] Ester Uridine 5′-(Trihydrogen diphosphate) (UDP-GlcN-
1
TFA, 29). White fluffy powder; H NMR (600 MHz, D2O): δ (ppm)
7.88 (d, J = 8.11 Hz, 1H), 5.90 (m, 2H), 5.58−5.51 (dd, 1H, J = 7.0
Hz, 3.2 Hz), 4.29 (m, 2H), 4.21 (s, 1H), 4.20−4.14 (m, 1H), 4.11
(ddd, J = 11.68, 5.39, 3.12 Hz, 1H), 4.04 (d, J = 10.57 Hz, 1H), 3.88
(dd, J = 20.10, 9.82 Hz, 2H), 3.81 (d, J = 11.83 Hz, 1H), 3.78−3.73
(m, 1H), 3.52 (dd, J = 9.53, 5.39 Hz, 1H); 13C NMR (150 MHz,
D2O): δ (ppm) 166.4, 160.0, 151.9, 141.8, 117.0, 102.7, 93.9, 88.5,
83.2, 73.9, 73.1, 70.3, 69.7, 69.5, 64.9, 60.2, 54.4; HRMS-FAB: [M −
H] calcd for C17H23F3N3O17P2− 660.0460; found: 660.0463.
P′-[2-Deoxy-2-[(1-oxo-2-ethen-1-yl)amino]-2-deoxy-α-D-glu-
copyranosyl] Ester Uridine 5′-(Trihydrogen diphosphate)
(UDP-GlcN-ene, 30). White fluffy powder; 1H NMR (800 MHz,
D2O): δ (ppm) 7.88 (d, J = 8.09 Hz, 1H), 6.35−6.29 (dd, J = 10.4,
18.4 Hz, 1H), 6.19−6.13(d, J = 16.8 Hz, 1H), 5.92−5.86 (m, 2H),
5.74−5.68 (d, J = 10.4 Hz, 1H), 5.46−5.42 (m, 1H), 4.31−4.25 (m,
2H), 4.21−4.18 (m, 1H), 4.18−4.08 (m, 2H), 3.97−3.93 (m, 1H),
3.88−3.84 (m, 1H), 3.78−3.73 (m, 3H), 3.50−3.46 (m, 1H); 13C
NMR (200 MHz, D2O): δ (ppm) 168.7, 166.1, 151.7, 141.4, 129.6,
127.9, 102.5, 94.4, 88.3, 83.1, 73.7, 72.9, 70.9, 69.5, 69.3, 64.8, 60.1,
53.6; HRMS-FAB: [M − H] calcd for C18H26N3O17P2−618.0743;
found: 618.0741.
2-Deoxy-2-[(trifluoroacetyl)amino]-D-glucopyranose-1-(di-
1
hydrogen phosphate) (22). H NMR (500 MHz, D2O): δ (ppm)
5.44 (dd, J = 7.32, 3.23 Hz, 1H), 4.03 (ddd, J = 10.57, 3.17, 1.84 Hz,
1H), 3.94 (ddd, J = 10.12, 4.89, 2.22 Hz, 1H), 3.77 (dd, J = 12.38, 4.94
Hz, 1H), 3.87 (ddd, J = 12.31, 9.99, 5.66 Hz, 1H), 3.51 (dd, J = 10.06,
9.14 Hz, 1H); 13C NMR (125 MHz, D2O): δ (ppm) 159.4, 116.7,
92.6, 72.6, 69.9, 69.5, 60.2, 54.3; HRMS-FAB: [M − H] calcd for
C8H12F3NO9P− 354.0207; found: 354.0206.
2-Deoxy-2-[(1-oxo-2-ethen-1-yl)amino]-β-D-glucopyranose-
1,3,4,6-tetraacetate (24). Et3N (145 μL, 1.04 mmol) was added to a
stirred solution of 1,3,4,6-O-acetyl-2-amino-2-deoxy-β-D-glucopyrano-
se·HCl (200 mg, 0.521 mmol). The solution was cooled to 0 °C, and
acryloyl chloride (50 μL, 0.625 mmol) was added dropwise. The
reaction mixture was stirred overnight at room temperature. The
solution was concentrated in vacuo and purified on silica gel
chromatography (hexanes 100% to hexanes/EtOAc = 1/1) to afford
1
24 as a clear syrup (170 mg, 81%). H NMR (500 MHz, CDCl3): δ
(ppm) 6.96 (d, J = 9.59 Hz, 1H), 6.20 (d, J = 17.1 Hz, 1H), 6.00 (dd, J
= 17.1, 10.4 Hz, 1H), 5.68 (d, J = 8.8 Hz, 1H), 5.61 (d, J = 9 Hz, 1H),
5.17 (t, J = 11 Hz, 1H), 5.07 (t, J = 9.65 Hz, 1H), 4. 34 (dd, J = 19.42,
9.61 Hz, 1H), 4.21 (td, J = 9.10, 4.57 Hz, 1H), 4.08 (dd, J = 12.44,
2.15 Hz, 1H), 3.81 (ddd, J = 9.85, 4.55, 2.19 Hz, 1H), 2.04−1.95 (s,
12H); 13C NMR (125 MHz, CDCl3): δ (ppm) 171.2, 170.9, 169.7,
169.4, 166.0, 130.1, 127.4, 92.4, 72.6, 72.6, 68.0, 61.7, 61.7, 52.5, 50.3;
P′-[2-(Acetylamino)-2-deoxy-α-D-galactopyranosyl] Ester
1
Uridine 5′-(Trihydrogen diphosphate), (UDP-GalNAc, 31). H
NMR (500 MHz, D2O): δ (ppm) 7.79 (d, J = 8.2 Hz, 1 H), 5.81 (br d,
J = 4.2 Hz, 1 H); 5.79 (br d, J = 8.3, 1 H); 5.39 (dd, J = 6.9, 3.3 Hz, 1
H); 4.22−4.19 (m, 2 H), 4.13−4.08 (m, 3 H), 4.05−4.01 (m, 2 H);
3.88 (d, J = 3.0 Hz, 1 H), 3.78 (dd, J = 11.8, 3.2 Hz, 1 H); 3.73 (m, 1
H), 3.62 (m, 1H), 1.92 (s, 3 H); HRMS-FAB: [M] calcd for
+
HRMS-FAB: [M + H] calcd for C17H24NO10 402.1400; found:
402.1395.
2-Deoxy-2-[(1-oxo-2-ethen-1-yl)amino]-α-D-glucopyranose-
1
+
3,4,6-triacetate-1-(dihydrogen phosphate) (25). Brown oil; H
C17H27N3O17P2 607.0816; found: 607.0818.
NMR (500 MHz, MeOD): δ (ppm) 6.28 (d, J = 9.92 Hz, 17 Hz, 1H),
6.22 (dd, J = 17.5, 2.05 Hz,1H), 5.66 (dd, J = 9.93, 2.05 Hz, 1H), 5.52
(dd, J = 6.63, 3.26 Hz, 1H), 5.36 (dd, J = 10.49, 9.59 Hz, 1H), 5.11 (t,
J = 9.75, 9.75 Hz, 1H), 4.39−4.34 (m, 1H), 4.31 (dd, J = 9.20, 6.05 Hz,
2H), 4.29−4.26 (m, 1H), 4.17−4.11 (m, 1H), 2.00 (s, 6H), 1.94 (s,
3H); 13C NMR (125 MHz, MeOD): δ (ppm) 171.1, 170.5, 169.9,
166.7, 130.3, 126.1, 93.7, 71.4, 68.3, 68.2, 61.5, 51.9, 50.3 ; HRMS-
FAB: [M − H] calcd for C15H21NO12P− 438.0807; found: 438.0800.
2-Deoxy-2-[(1-oxo-2-ethen-1-yl)amino]-α-D-glucopyranose-
3,4,6-triacetate-1-(dihydrogen phosphate) (26). Light brown
P′-[2-(1-Oxo-2-propyn-1-yl)amino-2-deoxy-α-D-galactopyra-
nosyl] Ester Uridine 5′-(Trihydrogen diphosphate) (UDP-GalN-
1
alkyne, 32). White fluffy powder; H NMR (600 MHz, D2O): δ
(ppm) 7.87 (d, J = 8.1 Hz, 1 H), 5.89 (d, J = 4.8 Hz, 1 H), 5.86 (d, J =
8.2 Hz, 1 H), 5.50 (dd, J = 3.4, 6.9 Hz, 1 H), 4.28 (m, 2 H), 4.22 (dt, J
= 3.1, 10.6 Hz, 1 H), 4.20 (m, 1 H), 4.17 (m, 1 H), 4.11−4.09 (m, 2
H), 3.97 (br d, J = 3.0 Hz, 1 H), 3.91 (dd, J = 3.1, 10.9 Hz, 1 H),
3.70−3.64 (m, 3 H); 13C NMR (150 MHz, D2O): δ (ppm) 166.2,
155.0, 151.8, 141.6, 102.6, 94.2, 88.4, 83.2, 83.1, 73.7, 72.0, 69.7, 68.3,
67.5, 65.0, 60.9, 50.3, 50.2; HRMS-FAB: [M] calcd for
1
+
amorphous solid; H NMR (500 MHz, D2O): δ (ppm) 6.14 (dd, J =
C18H25N3O17P2 617.0659; found: 617.0661.
1454
dx.doi.org/10.1021/jo202322k | J. Org. Chem. 2012, 77, 1449−1456