2684
P. Rota et al. / Tetrahedron: Asymmetry 21 (2010) 2681–2686
(CH2CH2CH2); ESI-MS (positive) m/z 300.3 [M+Na]+. Anal. Calcd for
16H23NO3: C, 69.29; H, 8.36; N, 5.05. Found: C, 69.39; H, 8.42; N,
5.09.
raphy, (eluting with hexane/AcOEt; 6:4, v/v) compound 3c was ob-
C
tained (122 mg, 89% Y) as a glass: ½a D20
ꢁ
¼ ꢀ22:5 (c 1, CHCl3); 1H
NMR (CDCl3) d 6.83 (d, JNH,2 = 9.1 Hz, 1H, N–H), 5.48 (ddd,
J4,3b = J4,5 = 11.0, J4,3a = 5.0 Hz, 1H, H-4), 5.28 (dd, J7,8 = 5.7,
J7,6 = 1.7 Hz, 1H, H-7), 5.09 (ddd, J8,9b = J8,7 = 5.7, J8,9a = 2.4 Hz, 1H,
H-8), 4.47 (dd, J9a,9b = 12.5, J9b,8 = 5.7 Hz, 1H, H-9a), 4.36 (dd,
J6,5 = 10.5, J6,7 = 1.7 Hz, 1H, H-6), 4.14 (dd, J9b,9a = 12.5,
J9b,8 = 5.7 Hz, 1H, H-9b), 3.99 (m, 1H, H-5), 3.80 (s, 3H, COOCH3),
2.62 (dd, J3a,3b = 13.5, J3a,4 = 5.0 Hz, 1H, H-3a) 2.16 (overlapping,
6H, 2 ꢂ CH3COO), 2.06 (s, 3H, CH3COO), 2.05–2.00 (overlapping,
7H; 2 ꢂ CH3COO and H-3b); 13C NMR (CDCl3) d 170.5, 170.4,
170.3, 170.12, 168.2, 166.1, 157.9 (1C, COCF2CF2CF3), 120.0–108.0
(3C, COCF2CF2CF3), 97.1, 71.3, 70.9, 67.6, 67.1, 61.8, 53.3, 50.6,
35.9, 20.7, 20.6 (3C) 20.5; IR 1752, 1715, 1669 cmꢀ1; MS (ESI posi-
tive) m/z 710.6 [M+Na]+. Anal. Calcd for C24H28F7NO14: C, 41.93; H,
4.11; N, 2.04. Found: C, 41.89; H, 4.08; N, 2.07.
4.5. General procedure for N-Perfluorotransacylation
The acylamide (0.2 mmol) dissolved in CH3CN (0.60 mL), con-
taining triethylamine (0.166 mL, 1.2 mmol), was reacted with the
appropriate perfluorinated anhydride (0.6 mmol) at 135 °C for
the time indicated in Table 2 (5–15 min) in a sealed tube. Then,
methanol (0.20 mL) was added and the reaction mixture was
cooled at 0 °C under stirring that was continued for 5 min. At this
time the solvent was evaporated under reduced pressure to afford
a crude residue which, after the usual work-up, and rapid chroma-
tography, eluting with the designed solvent system, afforded the
appropriate N-transacylated derivative. No methanol was added
to the reaction mixture, affording the compound 5b which was iso-
lated by rapid chromatography of the crude reaction residue, after
evaporation of the solvents.
4.9. Methyl-4,7,8,9-tetra-O-acetyl-N-(2,2,3,3,4,4,
4heptafluorobutanoyl)-b-neuraminic acid methyl ester 3d
4.6. 2,4,7,8,9-Penta-O-acetyl-5-N-(2,2,2-trifluoroacetyl)-b-neur-
aminic acid methyl ester 3a
Starting with methyl 4,7,8,9-tetra-O-acetyl-N-acetyl-b-neuram-
inic acid methyl ester 1b13 (90 mg, 0.2 mmol), after flash chroma-
tography, eluting with hexane/AcOEt (6:4; v/v), compound 3d was
Starting with 4,7,8,9-tetra-O-acetyl-5-N-acetyl-b-neuraminic
acid methyl ester 1a13 (107 mg, 0.2 mmol), after flash chromatogra-
phy, (eluting with hexane/AcOEt; 6:4, v/v), compound 3a was ob-
obtained (116 mg, 88% Y) as a glass: ½a D20
¼ þ2:0 (c 1, CHCl3); MS
ꢁ
(ESI negative) m/z 657.7 [MꢀH]ꢀ. Anal. Calcd for C23H28F7NO13
:
C, 41.89; H, 4.28; N, 2.12. Found: C, 42.45; H, 4.30; N, 2.09. Other
spectroscopic properties (1H and 13C NMR) were identical to those
previously reported.6
tained (100 mg, 85% Y) as a glass: ½a D20
ꢁ
¼ ꢀ22:3 (c 1, CHCl3); 1H
NMR (CDCl3) d 6.60 (d, JNH,2 = 9.2 Hz, 1H, N–H), 5.43 (m, 1H, H-4),
5.37 (m, 1H, H-7), 5.12 (m, 1H, H-8), 4.51 (d, J9a,9b = 12.5, 1H, H-
9a), 4.31 (br d, J6,5 = 10.5, 1H, H-6), 4.17 (dd, J9b,9a = 12.5,
J9b,8 = 5.8 Hz, 1H, H-9b), 4.08 (m, 1H, H-5), 3.83 (s, 3H, COOCH3),
2.62 (br d, J3a,3b = 13.4 Hz, 1H, H-3a), 2.18 (overlapping, 6H,
2 ꢂ CH3COO), 2.16–2.02 (overlapping, 4H, CH3COO and H-3b), 2.06
(overlapping, 6H, 2 ꢂ CH3COO); 13C NMR (CDCl3) d 171.1, 170.8,
170.6, 170.1, 168.2, 166.1, 157.4 (q, JC–F = 38 Hz, COCF3), 116.6 (1C,
JC–F = 287 Hz, CF3), 97.3, 71.8, 71.7, 67.7, 67.5, 62.0, 53.3, 49.9, 35.8,
20.9, 20.7, 20.6, 20.5; IR 1752, 1725, 1671 cmꢀ1; MS (ESI positive)
4.10. 4,8-Diacetyl-2-benzyloxycarbonyl-9-(2-methoxyethoxy)
methyl-N-(2,2,3,3,4,4,4-heptafluorobutanoyl)-b-neuraminic
acid 1,7-lactone 5a
Starting with 4,8-diacetyl-2-benzyloxycarbonyl-9-(2-methoxy-
ethoxy)methyl-N-acetyl-b-neuraminic acid 1,7-lactone1 (120 mg,
0.2 mmol), after a flash chromatography, eluting with hexane/
AcOEt; 6:4, v/v) the lactone 5a (119 mg, 79% Y) was obtained as
m/z 610.0 [M+Na]+, 1197.1 [2M+Na]+. Anal. Calcd for C22H28F3NO14
:
a glass (79% Y): ½a D20
ꢁ
¼ þ18:1 (c 1, CHCl3); 1H NMR (CDCl3) d
C, 45.98; H, 4.80; N, 2.38. Found: C, 45.94; H, 4.78; N, 2.35.
7.39–7.32 (5H, m, Ph), 7.08 (d, JNH,5 = 8.0 Hz, 1H, N–H), 5.46 (m,
1H, H-8), 5.18 (AB system, 2H, CH2Ph), 5.14 (br m, 1H, H-4), 4.79
(d, J8,7 = 7.8 Hz, 1H, H-7), 4.74 (m, 2H, OCH2O), 4.38 (br s, 1H, H-
6), 4.25 (br d, JNH,5 = 8.0 Hz, 1H, H-5), 3.99 (A part of ABX system,
J9a,9b = 11.6 Hz, J9a,8 = 3.3 Hz, 1H, H-9a), 3.88 (B part of ABX system,
J9a,9b = 11.6 Hz, J9b,8 = 2.7 Hz, 1H, H-9b), 3.70 (m, 2H, OCH2CH2O),
3.56 (m, 2H, OCH2CH2O), 3.38 (s, 3H, CH3O), 2.43 (br d,
J3a,3b = 15.0 Hz, 1H, H-3a), 2.16 (dd, J3b,3a = 15.0, J3b,4 = 3.9 Hz, 1H,
H-3b), 2.10 (s, 3H, CH3CO), 2.06 (s, 3H, CH3CO); 13C NMR (CDCl3)
d 169.8 (CH3COO at C-8), 168.7 (CH3COO at C-4), 163.9 (C-1),
157.3 (COCF2CF2CF3), 151.5 (PhCH2OCO), 133.9, 128.9, 128.7,
128.5 (Ph), 120.0–107.0 (CF2CF2CF3), 95.5 (OCH2O), 92.7 (C-2),
76.0 (C-7), 71.6 (C-6), 71.3 (OCH2CH2O), 71.2 (C-8), 70.9 (PhCH2O-
CO), 66.9 (C-4), 66.8 (OCH2CH2O), 64.9 (C-9), 59.0 (CH3O), 49.1 (C-
5), 33.0 (C-3), 20.9 (CH3COO at C-8), 20.6 (CH3COO at C-4); MS (ESI
positive) m/z 774.6 [M+Na]+. Anal. Calcd for C29H32F7NO14: C,
46.35; H, 4.29; N, 1.86. Found: C, 46.20; H, 4.31; N, 1.78.
4.7. 2,4,7,8,9-Penta-O-acetyl-5-N-(2,2,3,3,3-pentafluoroprop-
yonil)-b-neuraminic acid methyl ester 3b
Starting with 4,7,8,9-tetra-O-acetyl-5-N-acetyl-b-neuraminic
acid methyl ester 1a13 (107 mg, 0.2 mmol), after flash chromatog-
raphy, (eluting with hexane/AcOEt; 6:4, v/v) compound 3b was ob-
tained (110 mg, 86% Y) as a glass: ½a D20
ꢁ
¼ ꢀ18:5 (c 1, CHCl3); 1H
NMR (CDCl3)
d 7.00 (d, JNH,2 = 9.2 Hz, 1H, N–H), 5.42 (ddd,
J4,3b = J4,5 = 10.8, J4,3a = 4.8 Hz, 1H, H-4), 5.32 (m, 1H, H-7), 5.04
(br s, 1H, H-8), 4.51 (d, J9a,9b = 12.5, 1H, H-9a), 4.30 (br d,
J6,5 = 10.6, 1H, H-6), 4.16 (dd, J9b,9a = 12.5, J9b,8 = 6.5 Hz, 1H, H-9b),
4.08 (m, 1H, H-5), 3.85 (s, 3H, COOCH3), 2.58 (dd, J3a,3b = 13.4,
J3a,4 = 4.8 Hz, 1H, H-3a) 2.15 (overlapping, 6H, 2 ꢂ CH3COO),
2.09–2.05 (overlapping, 4H, CH3COO and H-3b), 2.03 (s, 3H,
CH3COO), 2.02 (s, 3H, CH3COO); 13C NMR (CDCl3) d 170.8, 170.6,
170.5, 170.1, 168.2, 166.1, 158.2 (COCF2CF3), 120.0–112.0 (2C,
CF2CF3), 97.1, 71.6, 71.4, 67.6, 67.3, 61.9, 53.3, 50.1, 35.9, 20.9,
20.7, 20.6, 20.5; IR 1747, 1718, 1669 cmꢀ1; MS (ESI positive) m/z
4.11. 2-Benzyloxycarbonyl-4,8,9-tri-trimethylsilyl-N-
(2,2,3,3,4,4,4-heptafluorobutanoyl)-b-neuraminic acid 1,7-
lactone 5b
660.0 [M+Na]+, 1298.3 [2M+Na]+. Anal. Calcd for C23H28F5NO14
C, 43.34; H, 4.43; N, 2.20. Found: C, 43.28; H, 4.47; N, 2.23.
:
Starting with 2-benzyloxycarbonyl-4,8,9-tri-trimethylsilyl-N-
acetyl-b-neuraminic acid 1,7-lactone 4b (130 mg, 0.2 mmol), after
rapid flash chromatography (eluting with hexane/AcOEt/Et3N;
9:1:0.1, v/v/v), compound 5b was obtained (118 mg, 74% Y) as a
4.8. 2,4,7,8,9-Penta-O-acetyl-N-(2,2,3,3,4,4,4-
heptafluorobutanoyl)-b-neuraminic acid methyl ester 3c
Starting with 4,7,8,9-tetra-O-acetyl-5-N-acetyl-b-neuraminic
acid methyl ester 1a13 (107 mg, 0.2 mmol), after flash chromatog-
glass: ½a 2D0
ꢁ
¼ þ69:1 (c 1, CHCl3); 1H NMR (CD2Cl2) d 7.41–7.33
(m, 5H, Ph), 6.87 (d, JNH,5 = 7.6 Hz, 1H, N–H), 5.22 (d,