Oligosaccharide Synthesis
FULL PAPER
79.2 (C-4b), 79.6 (C-4a), 93.5 (C-1a), 101.9 (CHPh), 102.1 (C-1b), 126.3,
127.0, 127.88, 127.93, 127.97, 128.2, 128.48, 128.55, 129.1, 137.2, 137.8,
138.1, 139.2; 1J1a-C,1a-H =163.3, 1J1b-C,1b-H =158.4 Hz; MALDI MS (positive
mode): m/z: 972.6 [M+Na]+, 988.6 [M+K]+: elemental analysis calcd
(%) for C54H67NO12Si (950.2): C 68.26, H 7.11, N 1.47; found: C 68.28, H
7.13, N 1.67.
0.599 mmol) in dry pyridine (10 mL) and the reaction mixture stirred
overnight (12 h) at RT. The solvent was evaporated in vacuo and coeva-
porated three times (15 mL) with toluene. Flash chromatography (tolu-
ene/ethyl acetate 12:1 ! 6:1) gave compound 29 (0.676 g, 0.515 mmol,
86%) as a white foam. Rf =0.61 (toluene/ethyl acetate 4:1); [a]D =ꢁ3.18
1
(c=1.0, CHCl3); H NMR (600 MHz, CDCl3): d=0.02 (s, 3H, CH3), 0.11
(s, 3H, CH3), 0.68–0.74 (m, 12H, 4 CH3), 1.46–1.48 (m, 1H, (CH3)2CH),
1.69–1.82 (m, 6H, 2 CH3), 3.45–3.50 (m, 2H, 5a-H, 5b-H), 3.69 (brs, 2H,
6a-H, 6a’-H), 3.90 (dd, 3J2a,1a =8.3, 3J2a,3a =10.5 Hz, 1H, 2a-H), 3.99–4.02
(m, 2H, 2b-H, 4b-H), 4.06 (t, 1H, 4a-H), 4.11–4.16 (m, 2H, 3a-H, 9-H
(Fmoc)), 4.26–4.41 (m, 6H, 6b-H, 6b’-H, 2 COCHHOPh, 2 OCHH
(Fmoc)), 4.52 (d, Jgem =12.9 Hz, 1H, OCHHPh), 4.56–4.59 (m, 3H, 3
Thexyldimethylsilyl O-(2-O-benzyl-4,6-O-benzylidene-3-O-phenoxyace-
tyl-b-d-mannopyranosyl)-(1!4)-3,6-di-O-benzyl-2-deoxy-2-dimethylma-
leimido-b-d-glucopyranoside (27): Phenoxyacetyl chloride (169 mL,
1.20 mmol) was added dropwise at 08C to a solution of compound 26
(0.95 g, 1.00 mmol) in dry pyridine (10 mL). After 1 h the reaction was
quenched with methanol (1 mL). The reaction mixture was evaporated in
vacuo and coevaporated with toluene (310 mL). Flash chromatography
(petroleum ether/ethyl acetate 6:1 ! 2:1) gave compound 27 (1.07 g,
0.988 mmol, 99%) as a white foam. Rf =0.69 (toluene/ethyl acetate 3:1);
[a]D =ꢁ14.08 (c=1.0, CHCl3); 1H NMR (600 MHz, CDCl3): d=ꢁ0.01 (s,
3H, CH3), 0.12 (s, 3H, CH3), 0.69–0.77 (m, 12H, 4 CH3), 1.46–1.49 (m,
1H, (CH3)2CH), 1.76–1.83 (m, 6H, 2 CH3), 3.22–3.26 (m, 1H, 5b-H),
3.46–3.48 (d, 1H, 5a-H), 3.56 (t, 1H, 6b-H), 3.67 (brs, 2H, 6a-H, 6a’-H),
OCHHPh), 4.62 (d,
J
gem =12.1 Hz, 1H, OCHHPh), 4.69 (d, Jgem
=
=
=
3
12.2 Hz, 1H, OCHHPh), 4.76 (s, 1H, 1b-H), 4.89 (dd, 3J3b,2b =2.9, J3b,4b
9.7 Hz, 1H, 3b-H), 4.92 (d, Jgem =12.3 Hz, 1H, OCHHPh), 4.95 (d, Jgem
3
12.9 Hz, 1H, OCHHPh), 5.16 (d, J1a,2a =8.3 Hz, 1H, 1a-H), 6.81–7.73 (m,
33H, Ph); 13C NMR (151 MHz, CDCl3): d=ꢁ3.9, ꢁ1.9, 18.3, 18.4, 19.7,
19.9, 33.9, 46.5, 57.4 (C-2a), 64.9, 66.4 (C-6b), 68.6 (C-6a), 69.9, 72.9 (C-
4b), 73.2 (C-5b), 73.5, 74.0, 74.6, 74.7 (C-5a), 74.8, 75.9 (C-2b), 76.8 (C-
3b), 77.2 (C-3a), 79.2 (C-4a), 93.4 (C-1a), 100.9 (C-1b), 114.5, 119.9,
121.8, 125.25, 125.28, 126.8, 127.09, 127.12, 127.70, 127.74, 127.9, 128.26,
128.32, 128.47, 128.50, 129.6, 137.7, 137.9, 138.4, 139.4, 141.1, 141.2,
3
3
3.89 (dd, J2a,1a =8.2, J2a,3a =10.6 Hz, 1H, 2a-H), 3.97 (d, 1H, 2b-H), 4.00–
4.05 (m, 2H, 4a-H, 4b-H), 4.12 (t, 1H, 3a-H), 4.17–4.19 (m, 1H, 6b’H),
4.41 (d, Jgem =16.2 Hz, 1H, COCHHOPh), 4.43 (d, Jgem =12.4 Hz, 1H,
1
1
143.36, 143.49, 154.9, 168.3, J1a-C,1a-H =163.4, J1b-C,1b-H =158.6 Hz; MALDI
MS (positive mode): m/z: calcd for: 1308.6; found: 1331.4 [M+Na]+,
1346.3 [M+K]+; elemental analysis calcd (%) for C77H85NO16Si: C 70.67,
H 6.55, N 1.07; found: C 70.32, H 6.68, N 0.87.
OCHHPh), 4.53–4.58 (m, 2H, OCHHPh, COCHHOPh), 4.61 (d, Jgem
=
12.0 Hz, 1H, OCHHPh), 4.71 (d, Jgem =12.1 Hz, 1H, OCHHPh), 4.73 (s,
1H, 1b-H), 4.87 (d, Jgem =12.0 Hz, 1H, OCHHPh), 4.88 (d, Jgem =12.4 Hz,
3
1H, OCHHPh), 4.99 (dd, 3J3b,2b =3.1, J3b,4b =10.3 Hz, 1H, 3b-H), 5.17 (d,
3J1a,2a =8.2 Hz, 1H, 1a-H), 5.43 (s, 1H, CHPh), 6.80–7.32 (m, 25H, Ph);
13C NMR (151 MHz, CDCl3): d=ꢁ3.8, ꢁ1.8, 18.3, 18.4, 19.8, 19.9, 24.5,
34.0, 57.5 (C-2a), 64.9, 67.0 (C-5b), 68.5 (C-6b), 68.6 (C-6a), 73.0 (C-3b),
73.6, 74.3, 74.7 (C-5a), 75.4 (C-4b), 75.7, 76.6 (C-2b), 77.0 (C-3a), 77.2,
79.2 (C-4a), 93.5 (C-1a), 101.3 (C-1b), 101.6 (CHPh), 114.6, 121.7, 122.1,
126.2, 126.9, 127.8, 127.9, 127.97, 128.04, 128.3, 128.4, 128.6, 129.1, 129.5,
137.8, 138.1, 139.2, 157.6, 168.4; 1J1a-C,1a-H =163.3, 1J1b-C,1b-H =158.9 Hz;
MALDI MS (positive mode): m/z: 1105.6 [M+Na]+, 1121.6 [M+K]+; el-
emental analysis calcd (%) for C62H73NO14Si (1084.3): C 68.68, H 6.79, N
1.29; found: C 68.62, H 6.91, N 1.29.
[2,4-Di-O-benzyl-6-O-(9-fluorenylmethoxycarbonyl)-3-O-phenoxyacetyl-
b-d-mannopyranosyl]-(1!4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimi-
do-a/b-d-glucopyranose (30): HF·pyridine (0.76 mL, 4.81 mmol) was
added at RT to a solution of compound 29 (0.63 g, 0.481 mmol) in dry
THF (8 mL) and the reaction mixture was stirred overnight (12 h). The
solution was diluted with ethyl acetate (15 mL) and neutralized with satu-
rated NaHCO3 solution. The organic layer was separated and the aque-
ous layer extracted three times with ethyl acetate (30 mL) and the com-
bined organic layers were concentrated in vacuo. Flash chromatography
(toluene/ethyl acetate 4:1) gave compound 30 (485 mg, 0.414 mmol,
86%) as a white foam. Rf (a)=0.41, Rf (a)=0.24 (toluene/ethyl acetate
2:1); [a]D =+1.88 (c=1.0, CHCl3); 1H NMR (600 MHz, CDCl3): d=1.73
Thexyldimethylsilyl O-(2,4-di-O-benzyl-3-O-phenoxyacetyl-b-d-manno-
pyranosyl)-(1!4)-3,6-di-O-benzyl-2-deoxy-2-dimethylmaleimido-b-d-glu-
copyranoside (28): Compound 27 (0.9 g, 0.830 mmol) was dissolved in a
BH3·THF solution (c=1 molLꢁ1). At 08C TMSOTf (0.18 mL, 1.0 mmol)
was added dropwise. After 30 min the reaction mixture was stirred at RT
for an additional 1.5 h. The solution was neutralized with NEt3 (1 mL),
methanol was added and after 15 min the solution was evaporated in
vacuo and coevaporated three times with methanol (30 mL). Flash chro-
matography (toluene/ethyl acetate 7:1) gave compound 28 (693 mg,
0.639 mmol, 77%) as colourless oil. Rf =0.45 (toluene/ethyl acetate 3:1);
[a]D =ꢁ16.18 (c=1.0, CHCl3); 1H NMR (600 MHz, CDCl3): d=0.00 (s,
3H, CH3), 0.12 (s, 3H, CH3), 0.69–0.77 (m, 12H, 4 CH3), 1.47–1.50 (m,
1H, (CH3)2CH), 1.78–1.85 (m, 6H, 2 CH3), 3.19–3.22 (m, 1H, 5b-H),
3.46–3.52 (m, 2H, 5a-H, 6b-H), 3.65–3.71 (m, 3H, 6a-H, 6a’-H, 6b’-H),
3.88–3.95 (m, 3H, 2a-H, 2b-H, 4b-H), 4.01 (t, 1H, 4a-H), 4.14 (dd,
(brs, 6H, 2 CH3), 2.81 (s, 1H, 1a-OH), 3.36–3.41 (m, 1H, 5b-H), 3.51–
3.53 (m, 1= H, 5a-H), 3.64–3.73 (m, 2H, 6a-H, 6a’-H), 3.81 (dd, J2a,1a
=
3
2
8.7, 3J2a,3a =10.5 Hz, 1= H, 2a-H), 3.92–3.97 (m, 2H, 2b-H, 4b-H), 4.04–
2
4.73 (m, 181= H, 2a-H, 3a-H, 4a-H, 5a-H, 1b-H, 6b-H, 6b’-H, 9-H
2
(Fmoc), 2 CHH (Fmoc), 71= OCHHPh, 2 COCHHOPh), 4.77–4.81 (m,
2
1
1
1H, 3b-H), 4.97 (d, Jgem =12.9 Hz, = H, OCHHPh), 5.11–5.13 (m, = H,
2
2
1
1a-H), 5.21 (t, = H, 1a-H), 6.80–7.38 (m, 33H, Ph); 13C NMR (151 MHz,
2
CDCl3): d=46.6, 55.5 (C-2a,a), 57.4 (C-2a,b), 64.9 (C-6b,a), 66.4 (C-
6b,b), 68.3 (C-6a,a; C-6a,b), 70.0 (C-5a,a), 72.8, 73.1 (C-4b,a; C-4b,b),
73.2 (C-5b,a; C-5b,b), 73.7, 74.4, 74.7 (C-5a,b), 74.8, 75.0, 75.9 (C-2b,a;
C-2b,b), 76.8 (C-3b,a; C-3b,b), 77.0 (C-3a,a; C-3a,b), 78.8 (C-4a,b), 79.1
(C-4a,a), 92.8 (C-1a,a), 93.1 (C-1a,b), 100.6 (C-1b,a; C-1b,b), 114.5,
119.9, 121.8, 125.23, 125.28, 126.8, 127.1, 127.68, 127.76, 127.81, 127.95,
127.98, 128.05, 128.09, 128.33, 128.48, 128.67, 129.6, 136.8, 137.50, 137.75,
3
3J3a,2a =10.7, J3a,4a =8.8 Hz, 1H, 3a-H), 4.31 (brs, 2H, COCHHOPh), 4.42
1
141.2, 143.3, 143.5, 157.5, 168.2, 171.6, 1J1a(a)-C,1a(a)-H =176.0, J1a(b)-C,1a(b)-H
=
166.3, 1J1b-C,1b-H =158.2 Hz; MALDI MS (positive mode): m/z: calcd for
1202.3; found: 1188.1 [M+Na]+, 1204.3 [M+K]+; elemental analysis
calcd (%) for C69H67NO16·2H2O: C 68.93, H 5.61, N 1.16; found: C 68.94,
H 5.58, N 1.07.
(d, Jgem =12.3 Hz, 1H, OCHHPh), 4.53–4.59 (m, 4H, 4 OCHHPh), 4.67–
4.69 (m, 2H, 1b-H, OCHHPh), 4.85–4.87 (m, 2H, 3b-H, OCHHPh), 4.95
(d, Jgem =12.3 Hz, 1H, OCHHPh), 5.18 (d, 3J1a,2a =8.1 Hz, 1H, 1a-H),
6.79–7.36 (m, 25H, Ph); 13C NMR (151 MHz, CDCl3): d=ꢁ3.8, ꢁ1.8,
18.3, 18.4, 19.8, 19.9, 24.5, 34.0, 57.5 (C-2a), 61.8 (C-6b), 64.9, 68.4 (C-6a),
72.8 (C-4b), 73.5, 74.0, 74.8 (C-5a), 74.9, 75.4 (C-5b), 76.1 (C-2b), 76.7
(C-3b), 77.0 (C-3a), 78.5 (C-4a), 93.5 (C-1a), 100.2 (C-1b), 114.5, 121.8,
O-{[2,4-Di-O-benzyl-6-O-(9-fluorenylmethoxycarbonyl)-3-O-phenoxyace-
tyl-b-d-mannopyranosyl]-(1!4)-3,6-di-O-benzyl-2-deoxy-2-dimethylma-
leimido-b-d-glucopyranosyl}-trichloroacetimidate (4b): Trichloroacetoni-
trile (0.22 mL, 1.93 mmol) and NaH (5 mg) were added to a solution of
compound 30 (0.45 g, 0.386 mmol) in dry CH2Cl2 (3 mL). After stirring
for 30 min at RT, the reaction mixture was neutralized with silica gel.
Flash chromatography (petroleum ether/ethyl acetate 3:1) gave com-
pound 4b (454 mg, 0.347 mmol, 90%) as colourless oil. Compound 4b was
immediately used in the next reaction step. Rf =0.56 (toluene/ethyl ace-
tate 3:1); [a]D =+8.38 (c=1.0, CHCl3); 1H NMR (600 MHz, CDCl3): d=
1.71 (s, 6H, 2 CH3), 3.37–3.40 (m, 1H, 5b-H), 3.67–3.70 (m, 2H, 5a-H,
6a-H), 3.78–3.79 (m, 1H, 6a’-H), 3.95–3.99 (m, 2H, 2b-H, 4b-H), 4.13–
122.1, 127.1, 127.3, 127.69, 127.73, 127.83, 128.17, 128.33, 128.43, 128.52,
1
129.6, 137.8, 138.0, 138.3, 139.0, 157.0, 168.3, 1J1a-C,1a-H =163.3, J1b-C,1b-H
=
158.3 Hz; MALDI MS (positive mode): m/z: calcd for: 1086.3; found:
1107.8 [M+Na]+, 1123.8 [M+K]+; elemental analysis calcd (%) for
C62H75NO14: C 68.55, H 6.96, N 1.29; found: C 68.61, H 7.02, N 1.30.
Thexyldimethylsilyl O-[2,4-di-O-benzyl-6-O-(9-fluorenylmethoxycarbon-
yl)-3-O-phenoxyacetyl-b-d-mannopyranosyl]-(1!4)-3,6-di-O-benzyl-2-
deoxy-2-dimethylmaleimido-b-d-glucopyranoside (29): Fmoc-Cl (0.38 g,
1.50 mmol) was added to
a solution of compound 28 (650 mg,
Chem. Eur. J. 2006, 12, 1274 – 1290
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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