Synthesis of Glycoconjugate Vaccines for Candida albicans
2
4.98 (s, 1 H, 1b-H), 4.89 (d, J ) 11.4 Hz, 1 H, 1/2 CH2Ph),
as outlined above to give 12 (1.16 g, 82%): [R]D +1.2 (c 1.0,
1
4.81 (d, J1,2 )7.8 Hz, 1 H, 1c-H), 4.63-4.72 (m, 3 H, 3/2 CH2-
Ph), 4.39-4.56 (m, 13 H, 9/2 CH2Ph, 2a-H, 2b-H, 1a-H, OCH2-
CHdCH2), 4.15 (t, 3J ) 9.6 Hz, 1 H, 4b-H), 4.06 (m, 1 H,
CHCl3); H NMR (600 MHz, CDCl3) δ ) 7.11-7.39 (m, 45 H,
Ar), 5.79-5.85 (m, 1 H, OCH2CHdCH2), 5.19-5.22 (m, 1 H,
OCH2CHdCH2), 5.12-5.14 (m, 2 H, 1a-H, OCH2CHdCH2),
4.91-4.93 (m, 2 H, 1b-H, 1/2 CH2Ph), 4.49-4.85 (m, 13 H,
13/2 CH2Ph), 4.42 (m, 3 H, 2a-H, CH2Ph), 4.34-4.36 (m, 3 H,
1c-H, CH2Ph), 4.12 (m, 1 H, 2b-H), 4.07 (m, 1 H, OCH2CHd
CH2), 4.02 (d, 3J ) 1.8 Hz, 1 H, 2c-H), 3.91-3.94 (m, 4 H, 3a-
3
OCH2CHdCH2), 3.87 (t, J ) 9.6 Hz, 1 H, 4a-H), 3.66-3.84
(m, 8 H, 2c-H, 3c-H, 6a-H, 6′a-H, 6b-H, 6′b-H, 6c-H, 6′c-H),
3.52s3.63 (m, 5 H, 5c-H, 3a-H, 4c-H, 3b-H, 5a-H), 3.43 (m, 1
H, 5b-H); 13C NMR (125 MHz, CDCl3), 139.2-138.1, 133.8,
128.4-127.2, 117.4, 105.3, 100.1, 99.9, 86.7, 80.2, 80.1, 77.3,
75.6, 75.4, 74.9, 74.8, 74.7, 74.6, 74.1, 73.6, 73.4, 73.3, 71.1,
70.3, 70.2, 69.8; EMS calcd for C84H90O16Na 1377.6, found
1378.0.
3
H, 3b-H, 6b-H, 6′b-H), 3.87 (t, J ) 9.0 Hz, 1 H, 4c-H), 3.83
(m, 1H, OCH2CHdCH2), 3.64-3.78 (m, 7 H, 4a-H, 4b-H, 5b-
H, 5a-H, 6a-H, 6′a-H, 6c-H), 3.59 (m, 1 H, 6′c-H), 3.33 (d, 3J )
9.0 Hz, 1 H, 3c-H), 3.19 (m, 1 H, 5c-H); 13C NMR (125 MHz,
CDCl3), 138.7-138.1, 133.9, 128.5-127.4, 117.2, 99.6, 98.2,
97.3, 81.0, 80.3, 77.3, 75.2, 75.1, 75.0, 74.8, 74.7, 74.5, 74.3,
74.1, 73.4, 73.3, 73.2, 72.8, 72.0, 71.9, 71.6, 71.1, 70.8, 69.5,
69.3, 67.9, 67.8; ES HRMS calcd for C84H90O16Na 1377.612658,
found 1377.612657.
Allyl (3,4,6-Tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-
(3,4,6-tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-3,4,6-tri-
O-benzyl-â-D-mannopyranoside (8). The procedure used
was analogous to the preparation of 5 and used trisaccharide
7 (1.07 g, 0.79 mmol), dimethyl sulfoxide (10 mL), acetic
anhydride (5 mL), THF (10 mL), and L-Selectride (1 M, 3 mL).
Column chromatography in n-hexane/ethyl acetate (5:2) gave
the trisaccharide 8 (823 mg, 77%). The analytical data of
compound 8 were identical with the published values.18b
Allyl (2-O-Acetyl-3,4,6-tri-O-benzyl-â-D-glucopyrano-
syl)-(1f2)-(3,4,6-tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-
(3,4,6-tri-O-benzyl-R-D-mannopyranosyl)-(1f2)-3,4,6-tri-
O-benzyl-R-D-mannopyranoside (13). Allyl trisaccharide 12
(1.08 g) was glycosylated as outlined above to give 13 (1.08 g,
74%): [R]D -10.3 (c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3) δ
) 7.04-7.40 (m, 60 H, Ar), 5.78-5.84 (m, 1 H, OCH2CHdCH2),
5.17-5.20 (m, 1 H, OCH2CHdCH2), 5.15 (t, 3J ) 9.0 Hz, 1 H,
2d-H), 5.06-5.10 (m, 2 H, 1d-H, OCH2CHdCH2), 4.99 (s, 1 H,
Allyl (2-O-Acetyl-3,4,6-tri-O-benzyl-â-D-glucopyrano-
syl)-(1f2)-(3,4,6-tri-O-benzyl-R-D-mannopyranosyl)-(1f2)-
3,4,6-tri-O-benzyl-R-D-mannopyranoside (10). The proce-
dure used was analogous to the preparation of 3 and used
glycosyl donor 2 (1.52 g, 2.37 mmol), disaccharide 9 (1.83 g,
1.98 mmol), dichloromethane (10 mL), trimethylsilyl trifluo-
romethanesulfonate (7 µL), and activated 4 Å molecular sieves
(200 mg). Column chromatography in n-hexane/ethyl acetate
(6:1) gave the trisaccharide 10 (2.49 g, 90%): [R] D +9.6 (c 1.0,
2
1a-H), 4.95 (d, J ) 11.4 Hz, 1 H, 1/2 CH2Ph), 4.76-4.91 (m,
6 H, 1c-H, 1b-H, 2 CH2Ph), 4.41-4.69 (m, 18 H, 9 CH2Ph),
2
4.37 (d, J ) 11.4 Hz, 1 H, 1/2 CH2Ph), 4.22 (br, 1 H, 2a-H),
4.18 (d, 3J ) 3.0 Hz, 1 H, 2b-H), 4.07 (m, 1 H, OCH2CHdCH2),
4.04 (m, 1 H, 2c-H), 3.77-3.95 (m, 6 H, OCH2CHdCH2, 3d-H,
5a-H, 3a-H, 3c-H, 6c-H), 3.55-3.75 (m, 13 H, 4a-H, 4b-H, 4c-
H, 4d-H, 5c-H, 5d-H, 5b-H, 6a-H, 6′a-H, 6′c-H, 6d-H, 6b-H, 6′b-
H), 3.26-3.31 (m, 2 H, 6′d-H, 3b-H); 13C NMR (125 MHz,
CDCl3), 138.8-137.9, 133.8, 128.6-127.3, 117.2, 101.0, 99.5,
98.0, 83.5, 79.9, 78.2, 78.1, 76.8, 75.4, 75.2, 75.1, 75.0, 74.9,
74.8, 74.7, 74.5, 74.4, 73.5, 73.3, 73.2, 72.7, 72.3, 71.8, 71.7,
70.5, 69.6, 69.5, 69.3, 69.2, 69.1, 67.8; ES HRMS calcd for
1
CHCl3); H NMR (600 MHz, CDCl3) δ ) 7.19-7.40 (m, 45 H,
Ar), 5.79-5.85 (m, 1H, OCH2CHdCH2), 5.19-5.23 (m, 1 H,
OCH2CHdCH2), 5.11-5.13 (m, 1 H, OCH2CHdCH2), 5.08 (dd,
3J ) 8.4 Hz, 9.6 Hz, 1 H, 2c-H), 5.01 (d, J1,2 ) 2.4 Hz, 1 H,
1a-H), 4.97 (d, J1,2 ) 1.8 Hz, 1 H, 1b-H), 4.91 (d, 2J ) 10.8 Hz,
1 H, 1/2 CH2Ph), 4.66-4.87 (m, 8 H, 4 CH2Ph), 4.47-4.62 (m,
2
8 H, 4 CH2Ph), 4.42 (d, J ) 10.8 Hz, 1 H, 1/2 CH2Ph), 4.28
3
(m, 1 H, 1c-H), 4.19 (t, J ) 5.4 Hz, 1 H, 2a-H), 4.12 (m, 1H,
2b-H), 4.08 (m, 1 H, OCH2CHdCH2), 3.98 (dd, 3J ) 3.0 Hz,
9.0 Hz, 1 H, 3b-H), 3.91-3.93 (m, 2 H, 3a-H, 6a-H), 3.77-3.85
(m, 4 H, 4b-H, OCH2CHdCH2, 6′a-H, 6b-H), 3.71-3.74 (m, 3
H, 4a-H, 5b-H, 6′c-H), 3.58-3.68 (m, 4 H, 6c-H, 6′b-H, 4c-H,
C113H120O22Na 1851.816897, found 1851.817052.
Allyl (3,4,6-Tri-O-benzyl-â-D-glucopyranosyl)-(1f2)-
(3,4,6-tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-(3,4,6-tri-
O-benzyl-R-D-mannopyranosyl)-(1f2)-3,4,6-tri-O-benzyl-
R-D-mannopyranoside (14). Allyl tetrasaccharide 13 (1.08
g) was deacetylated as outlined above to give 14 (1.05 g,
100%): [R] D -26.7 (c 1.0, CHCl3); 1H NMR (600 MHz, CDCl3)
δ ) 6.93-7.42 (m, 60 H, Ar), 5.85-5.92 (m, 1 H, OCH2CHd
CH2), 5.26-5.29 (m, 1 H, OCH2CHdCH2), 5.18-5.20 (m, 1 H,
3
5a-H), 3.52 (t, J ) 9.0 Hz, 1 H, 3c-H), 3.88 (m, 1 H, 5c-H),
1.98 (s, 3 H, Ac); 13C NMR (125 MHz, CDCl3), 99.8, 99.4, 98.2,
82.6, 80.2, 77.9, 77.6, 75.1, 75.0, 74.8, 74.7, 74.4, 73.5, 73.4,
73.0, 72.8, 72.7, 71.9, 71.1, 70.3, 69.4, 67.9; ES HRMS calcd
for C86H92O17Na 1419.623222, found 1419.623151.
2
OCH2CHdCH2), 5.15 (d, J1,2 ) 1.8 Hz, 1 H, 1b-H), 5.07 (d, J
Allyl (3,4,6-Tri-O-benzyl-â-D-glucopyranosyl)-(1f2)-
(3,4,6-tri-O-benzyl-R-D-mannopyranosyl)-(1f2)-3,4,6-tri-
O-benzyl-R-D-mannopyranoside (11). Allyl trisaccharide
(2.49 g) 10 was deacetylated using the protocol described above
) 11.4 Hz, 1 H, 1/2 CH2Ph), 4.86-5.02 (m, 7 H, 1a-H, 3 CH2-
Ph), 4.74-4.77 (m, 2 H, 2 CH2Ph), 4.68 (d, J1,2 ) 7.8 Hz, 1 H,
2
1d-H), 4.67 (d, J ) 11.4 Hz, 1 H, 1/2 CH2Ph), 4.53-4.64 (m,
1
8 H, 4 CH2Ph), 4.31-4.48 (m, 5 H, 2b-H, 2 CH2Ph), 4.14-4.20
(m, 3 H, 2c-H, 2a-H, 4b-H), 4.04 (s, 1 H, 1c-H), 3.87-3.97 (m,
5 H, 5b-H, 3a-H, 3b-H, 6d-H, 6′d-H), 3.78-3.82 (m, 4 H, 4c-H,
4a-H, 2d-H, 6′a-H), 3.63-3.74 (m, 7 H, 5a-H, 3d-H, 6b-H, 6′b-
to give 11 (2.42 g, 100%): [R]D +12.6 (c 1.0, CHCl3); H NMR
(600 MHz, CDCl3) δ ) 7.15-7.44 (m, 45 H, Ar), 5.79-5.85 (m,
1 H, OCH2CHdCH2), 5.19-5.22 (m, 1 H, OCH2CHdCH2),
5.11-5.13 (m, 2 H, 1a-H, OCH2CHdCH2), 4.95 (s, 1 H, 1b-
H), 4.87 (m, 2 H, CH2Ph), 4.77 (d, 2J ) 11.4 Hz, 1 H, 1/2 CH2-
Ph), 4.44-4.73 (m, 14 H, 7 CH2Ph), 4.35 (d, 2J ) 11.4 Hz, 1 H,
1/2 CH2Ph), 4.23 (m, 1 H, 1c-H), 4.13 (m, 1 H, 2a-H), 4.09 (m,
1 H, OCH2CHdCH2), 4.04 (m, 1 H, 2b-H), 4.0 (dd, 3J ) 3.0
Hz, 6.6 Hz, 1 H, 3a-H), 3.74-3.93 (m, 8 H, 3b-H, 4a-H, 4b-H,
OCH2CHdCH2, 5a-H, 6b-H, 6′b-H, 6a-H), 3.58-3.72 (m, 4 H,
5b-H, 6′a-H, 6c-H, 6′c-H), 3.42-3.52 (m, 3 H, 3c-H, 4c-H, 2c-
H), 3.36 (m, 1 H, 5c-H); 13C NMR (125 MHz, CDCl3), 139.0-
138.1, 133.9, 128.7-127.4, 117.0, 107.7, 100.5, 98.3, 84.2, 79.9,
77.5, 77.4, 77.3, 77.2, 77.0, 76.9, 76.8, 75.6, 75.3, 75.2, 75.1,
74.9, 74.7, 74.1, 73.5, 73.3, 73.2, 72.5, 72.4, 71.9, 69.6, 69.3,
67.9; ES HRMS calcd for C84H90O16Na 1377.612658, found
1377.612341.
3
H, 6c-H, 6′c-H, 6′a-H), 3.59 (m, 1 H, 5d-H), 3.55 (t, J ) 8.4
Hz, 1 H, 4d-H), 3.28 (dd, 3J ) 3.6 Hz, 9.6 Hz, 1 H, 3c-H), 3.07
(m, 1 H, 5c-H); 13C NMR (125 MHz, CDCl3), 139.1-137.9,
133.7, 128.6-127.2, 117.4, 105.3 (1JC-H ) 165 Hz), 99.2 (1JC-H
) 170 Hz), 97.98 (1JC-H ) 170 Hz), 97.8 (1JC-H ) 160 Hz), 86.6,
80.4, 78.9, 77.9, 77.3, 76.9, 76.8, 75.3, 75.2, 75.1, 74.9, 74.8,
74.7, 74.6, 74.2, 74.0, 73.7, 73.4, 73.3, 73.2, 73.1, 71.9, 71.7,
70.6, 69.8, 69.7, 69.4, 69.3, 69.1, 67.8; ES HRMS calcd. for
C111H118O21Na 1809.806332, found 1809.806374.
Allyl (3,4,6-Tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-
(3,4,6-tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-(3,4,6-tri-
O-benzyl-R-D-mannopyranosyl)-(1f2)-3,4,6-tri-O-benzyl-
R-D-mannopyranoside (15). Allyl tetrasaccharide (600 mg)
14 was oxidized, and the keto derivative was reduced as
Allyl (3,4,6-Tri-O-benzyl-â-D-mannopyranosyl)-(1f2)-
(3,4,6-tri-O-benzyl-R-D-mannopyranosyl)-(1f2)-3,4,6-tri-
O-benzyl-R-D-mannopyranoside (12). Allyl trisaccharide
(1.41 g) 11 was oxidized, and the keto derivative was reduced
outlined above to give 15 (480 mg, 80%): [R] -21.4 (c 1.0,
D
1
CHCl3); H NMR (600 MHz, CDCl3) δ ) 6.95-7.42 (m, 60 H,
Ar), 5.82-5.89 (m, 1 H, OCH2CHdCH2), 5.82-5.89 (m, 1 H,
J. Org. Chem, Vol. 70, No. 18, 2005 7387