June 1998
SYNTHESIS
907
1H NMR (CDCl3, 200.04 MHz): d = 1.95 (s, 3H, CH3), 2.01 (s, 6H, 2
´ CH3), 2.04 (s, 3H, CH3), 3.15 (d, J = 14.8 Hz, 1H, CHHCONH),
3.72 (m, 1H, H-5), 3.87 (d, J = 14.8 Hz, 1H, CHHCONH), 3.90 (s,
3H, OCH3), 3.97 (dd, J = 12.3, 2.2 Hz, 1H, 1H-6), 4.29 (dd, J = 12.3,
3.9 Hz, 1H, 1H-6), 4.89 (dd, J = 9.7, 9.5 Hz, 1H, H-2), 5.04 (m, 1H,
H-4), 5.15 (m, 2H, CH2Ph), 5.19 (m, 1H, H-1), 5.26 (dd, J = 9.5,
9.4 Hz, 1H, H-3), 6.27 (s, 1H, NH), 6.52 (br s, 1H, NH), 7.33 (m, 5H,
C6H5).
After 15 min the solution was washed with water (3 ´ 10 mL), the or-
ganic phase was dried (MgSO4) and concentrated in vacuo. The resi-
due was recrystallized from Et2O to give 6a (0.20 g, 90%); mp 193 °C;
[a]D23 +5.3 (c = 0.75, CHCl3).
MS (FAB): m/z (%) = 663 (M + Na+, 80), 641 (M + H+, 45), 529 (55),
355 (41).
IR (KBr): n = 3429, 3375, 3338, 1748, 1697, 1548, 1376, 1251, 1181,
1049 cm–1.
13C NMR (CDCl3, 50.30 MHz): d = 20.56 (4 ´ COCH3), 35.58
(CH2CONH), 54.42 (OCH3), 61.61 (C-6), 63.46 (q, J = 29 Hz, CCF3),
67.41 (CH2Ph), 68.12 (C-4), 70.46 (C-2), 72.78 (C-3), 73.73 (C-5),
78.09 (C-1), 123.44 (q, J = 288 Hz, CF3), 127.96, 128.39, 128.63,
135.65 (C-arom.), 154.32 (O2CNH), 166.18 (CO2Me), 168.28
(CH2CONH), 169.51, 169.92, 170.50, 170.62 (COCH3).
1H NMR (CDCl3, 200.04 MHz): d = 2.01 (s, 6H, 2 ´ CH3), 2.05 (s,
6H, 2 ´ CH3), 3.26 (d, J = 15.4 Hz, 1H, CHHCONH), 3.72 (m, 1H,
H-5), 3.97 (s, 3H, OCH3), 3.88 (d, J = 15.4 Hz, 1H, CHHCONH),
3.98 (dd, J = 12.4, 2.2 Hz, 1H, 1H-6), 4.20 (dd, J = 12.4, 4.4 Hz, 1H,
1H-6), 4.88 (t, J = 9.6, 9.2 Hz, 1H, H-2), 5.03 (dd, J = 10, 9.4 Hz, 1H,
H-4), 5.10 (dd, J = 9.4, 9.2 Hz, 1H, H-1), 5.25 (dd, J = 9.6, 9.2 Hz,
1H, H-3), 6.64 (d, J = 9.2 Hz, 1H, NH), 7.79 (s, 1H, NH).
13C NMR (CDCl3, 50.30 MHz): d = 20.94, 21.00, 21.08 (4 ´ COCH3),
35.52 (CH2CONH), 55.48 (OCH3), 62.19 (C-6), 63.39 (q, J = 31 Hz,
CCF3), 68.60 (C-4), 70.88 (C-2), 73.19 (C-3), 74.07 (C-5), 78.49 (C-
1), 115.57 (q, J = 289 Hz, CF3CO), 123.30 (q, J = 288 Hz, CF3),
19F NMR (CDCl3, 188.21 MHz): d = 2.55 (s, 3F, CF3).
3b: mp 80°C.
MS (FAB): m/z (%) = 701 (M + Na+, 13), 679 (M + H+, 31), 307 (23),
154 (100), 137 (69), 91 (31).
157.04 (q,
J = 38 Hz, CF3CO), 165.94 (CO2Me), 168.14
IR (KBr): n = 3440, 2985, 2960, 1754, 1634, 1543, 1509, 1374, 1236,
1042 cm–1.
(CH2CONH), 169.94, 170.43, 171.16, 171.21 (COCH3).
19F NMR (CDCl3, 188.21 MHz): d = 1.66 (s, 3F, CF3), 3.65 (s, 3F,
CF3).
1H NMR (CDCl3, 200.04 MHz): d = 2.00 (s, 3H, CH3), 2.02 (s, 6H,
2-CH3), 2.07 (s, 3H, CH3), 3.22 (d, J = 15.8 Hz, 1H, CHHCONH),
3.76 (m, 1H, H-5), 3.80 (d, J = 15.8 Hz, 1H, CHHCONH), 3.87 (s,
3H, OCH3), 4.06 (dd, J = 12.3, 2.2 Hz, 1H, 1H-6), 4.29 (dd, J = 12.3,
3.9 Hz, 1H, 1H-6), 4.88 (dd, J = 9.6, 9.5 Hz, 1H, H-2), 5.00 (m, 1H,
H-4), 5.04 (m, 2H, CH2Ph), 5.08 (m, 1H, H-1), 5.26 (dd, J = 9.5, 9.2
Hz, 1H, H-3), 6.30 (s, 1H, NH), 6.63 (br s, 1H, NH), 7.33 (m, 5H,
C6H5).
X-ray Analysis of 6a:11, 12
Crystal data for 6a (C22H26F6N2O13), crystal with the dimension
0.50 mm ´ 0.40 mm ´ 0.35 mm; monoclinic space group P21 (No. 4),
a = 8.195(1) Å, b = 8.540(1) Å, c = 20.651(1) Å, b = 95.25(1)°, V =
1439.2(3) Å3, Z = 2, rcal = 1.478 g·cm–3, R1 [Fo>4s(Fo)] = 0.0508,
wR2 [Fo>4s(Fo)] = 0.1394.
3C NMR (CDCl3, 50.30 MHz): d = 20.47, 20.55, 20.68 (4 ´ COCH3),
34.92 (CH2CONH), 54.33 (OCH3), 61.64 (C-6), 63.18 (q, J = 29 Hz,
CCF3), 66.97 ( CH2Ph), 68.11 (C-4), 70.29 (C-2), 72.63 (C-3), 73.68
(C-5), 78.33 (C-1), 123.47 (q, J = 288 Hz, CF3), 127.58, 128.29,
128.62, 135.82 (C-arom.), 154.21 (O2CNH), 166.26 (CO2Me),
168.03 (CH2CONH), 169.50, 169.88, 170.56, 171.39 (COCH3).
19F NMR (CDCl3, 188.21 MHz): d = 1.90 (s, 3F, CF3).
Methyl (2S)-2-Acetamido-N2-(benzyloxycarbonyl)-N4-[3,4,6-tri-
O-acetyl-2-deoxy-b-D-glucopyranosyl]-2-(trifluoromethyl)aspar-
aginate (9a) and Methyl (2R)-2-Acetamido-N2-benzyloxycarbon-
yl-N4-[3,4,6-tri-O-acetyl-2-deoxy-b-D-glucopyranosyl]-2-
(trifluoromethyl)asparaginate (9b):
MethodA: Compounds 9a and 9b were obtained following the proce-
dure described for 3a/3b using 8 (0.50 g, 1.4 mmol), 1 (0.50 g,
1.4 mmol), and DCC (0.29 g, 1.4 mmol). The two diastereomers were
separated by chromatography (EtOAc/hexanes 2:3) yielding 9a
(0.21 g, 22.5%) and 9b (0.21 g, 22.5%).
Method B: Applying the above described protocol we obtained from
8 (2 ´ 0.61 g, 1.75 mmol) and 7 (0.46 g, 1.4 mmol) on heating up to
80°C for 12 h a diastereomeric mixture which was separated by chro-
matography yielding 9a (0.25 g, 26.5%) and 9b (0.17 g, 18%).
Methyl (2S)-N4-[2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl]-2-
(trifluoromethyl)asparaginate (5a):
To a solution of compound 3a (0.26 g, 0.38 mmol) in MeOH (20 mL)
was added 10% Pd/C (50 mg). The mixture was stirred under H2 for
60 min then filtered. After removal of the solvent under reduced pres-
sure the residue was purified by crystallization from Et2O/petroleum
ether (50:50) to give 5a (0.19 g, 92%); mp 127°C.
MS (FAB): m/z (%) = 567 (M + Na+, 52), 545 (M + H+, 90), 355 (75),
327 (60).
9a: mp 182°C; [a]D23 –1.3 (c = 0.75, CHCl3).
IR (KBr): n = 3438, 3338, 2985, 1753, 1694, 1544, 1372, 1233, 1171,
1043 cm–1.
MS (FAB): m/z (%) = 700 (M + Na+, 30), 678 (M + H+, 68), 210 (15),
91 (100).
1H NMR (CDCl3, 200.04 MHz): d = 2.02 (s, 6H, 2-CH3), 2.08 (s, 6H,
2-CH3), 2.30 (br s, 2H, NH2), 2.57 (d, J = 16 Hz, 1H, CHHCONH),
3.00 (d, J = 16 Hz, 1H, CHHCONH), 3.77 (m, 1H, H-5), 3.80 (s, 3H,
OCH3), 4.07 (dd, J = 12.4, 2.2 Hz, 1H, 1H-6), 4.26 (dd, J = 12.4, 4.4
Hz, 1H, 1H-6), 4.92 (dd, J = 9.6, 9.4 Hz, 1H, H-2), 5.05 (dd, J = 10,
9.4 Hz, 1H, H-4), 5.21 (dd, J = 9.4, 9.2 Hz, 1H, H-l), 5.29 (dd, J =
9.6, 9.4 Hz, 1H, H-3), 7.21 (d, J = 9 Hz, 1H, NH).
IR (KBr): n = 3434, 2926, 1749, 1661, 1634, 1542, 1374, 1244, 1044
cm–1.
1H NMR (CDCl3, 200.04 MHz): d = 1.95 (s, 3H, CH3), 1.99 (s, 3H,
CH3), 2.02 (s, 3H, CH3), 2.06 (s, 3H, CH3), 3.10 (d, J = 15.4 Hz, 1H,
CHHCONH), 3.66 (m, 1H, H-5), 3.84 (d, J = 15.4 Hz, 1H, CHH-
CONH), 3.88 (s, 3H, OCH3), 3.98 (dd, J = 12.4, 2.2 Hz, 1H, 1H-6),
4.10 (m, 1H, H-2), 4.28 (dd, J = 12.4, 4.4 Hz, 1H, 1H-6), 4.95 (m, 1H,
H-1), 5.02 (m, 1H, H-3), 5.08 (m, 1H, H-4), 5.11 (m, 2H, CH2Ph),
5.93 (d, J = 8 Hz, 1H, NH), 6.33 (s, 1H, NH), 7.13 (d, J = 9 Hz, 1H,
NH), 7.33 (m, 5H, C6H5).
13C NMR (CDCl3, 50.30 MHz): d = 20.93, 20.98, 21.06 (4 ´ COCH3),
38.50 ( CH2CONH), 54.09 (OCH3), 62.08 (C-6), 63.48 (q, J = 28 Hz,
CCF3), 68.57 (C-4), 70.84 (C-2), 73.08 (C-3), 74.07 (C-5), 78.23 (C-
1), 124.50 (q, J = 286 Hz, CF3), 169.09 (CO2Me), 169.54
(CH2CONH), 170.08, 170.43, 171.13, 171.48 (COCH3).
19F NMR (CDCl3, 188.21 MHz): d = –0.96 (s, 3F, CF3).
13C NMR (CDCl3, 75.48 MHz): d = 20.89, 20.95, 21.01 (CH3CO2),
23.32 (CH3CONH), 35.88 (CH2CONH), 53.44 (C-2), 54.54 (OCH3),
62.22 (C-6), 63.71 (q, J = 30 Hz, CCF3), 67.68 (CH2Ph), 68.40 (C-4),
Methyl (2S)-N4-[2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl]-N2- 73.39 (C-5), 73.97 (C-3), 80.12 (C-1), 123.99 (q, J = 288 Hz, CF3),
(trifluoroacetyl)-2-(trifluoromethyl)asparaginate (6a):
128.45, 128.78, 129.04, 136.22 (C-arom.), 154.64 (O2CNH), 166.80
Compound 5a (0.19 g, 0.35 mmol) was added to a solution of pyridine (CO2Me), 169.01 (CH2CONH), 169.91, 171.17, 172.21, 172.32
(0.055 g, 0.7 mmol) in CH2Cl2 (5 mL). The mixture was stirred and (COCH3).
then trifluoroacetic anhydride (0.15 g, 0.70 mmol) was slowly added. 19F NMR (CDCl3, 188.21 MHz): d = 2.74 (s, 3F, CF3).