and trimethylsilyl trifluoromethanesulfonate (2.1 µl, 0.01 mmol)
was added. After 15 min, TLC analysis showed complete con-
sumption of the donor. The reaction was quenched by addition
of triethylamine. After filtration, the residue was washed with
DCM (50 ml) and the combined organic phases were concen-
trated in vacuo. The residue was dissolved in DCM (100 ml) and
the solution was washed subsequently with saturated aqueous
NaHCO3 (2 × 20 ml) and brine (20 ml), dried (MgSO4), filtered
and the filtrate concentrated in vacuo. Purification of the
residue by silica gel column chromatography (eluent: 2.5% ethyl
acetate in toluene) gave disaccharide 18 (165.2 mg, 60.2%) and
the corresponding β-anomer (51.7 mg, 18.1%), Rf = 0.39 (20%
(1 ml) and the solution was stirred at room temperature over
molecular sieves (300 mg, 4Å) for 1 h. In a second flask donor
7 (283.5 mg, 0.42 mmol) was dissolved in DCM (2 ml) and the
solution was stirred at room temperature over molecular sieves
(500 mg, 4Å) for 1 h. Both solutions were cooled to Ϫ20 ЊC and
TMSOTf (3.2 µl, 0.018 mmol) was added to the acceptor
solution. Subsequently, the donor solution was added to the
acceptor in portions (100 µl) over a period of 3 h. When
addition was complete, the reaction mixture was stirred for an
additional 30 minutes. The mixture was neutralized using tri-
ethylamine, filtered, and the filtrate was concentrated in vacuo.
The residue was dissolved in DCM (100 ml), washed succes-
sively with saturated aq. NaHCO3 (2 × 20 ml) and brine (1 × 20
ml), dried (MgSO4), filtered, and concentrated in vacuo. The
residue was purified by flash silica gel chromatography (eluent
20% ethyl acetate in hexanes), followed by Sephadex LH-20
size-exclusion column chromatography (50% methanol in
DCM) to give trisaccharide 20 (215 mg, 75%), Rf 0.33 (20%
ethyl acetate in hexanes); 1H NMR (500 MHz; CDCl3) δ 8.03–
7.70 (2m, 6H, o-ArH, Bz), 7.59–6.86 (m, 44H, ArH), 5.76 (ddd,
1
ethyl acetate in hexanes); H NMR (500 MHz; CDCl3) δ 8.13
(m, 2H, o-ArH, Bz), 7.71–7.14 (m, 30H, ArH), 6.88, 6.87 (2s,
2H, o-ArH, PMB), 5.91 (ddd, 0.5H, CH᎐CH , 3Jtrans = 16.7 Hz,
᎐
2
3Jcis = 10.8 Hz, 3J = 5.9 Hz), 5.57 (ddd, 0.5H, CH᎐CH ,
᎐
2
3
3
3Jtrans = 17.3 Hz, Jcis = 9.7 Hz, J = 7.0 Hz), 5.65, 5.64 (2d, 1H,
3
H-1Ј, J1Ј,2Ј = 5.5 Hz), 5.45–5.42 (m, 1H, H-2), 5.19, 5.08 (2dd,
3
3
2H, CH᎐CH , Jtrans = 17.3 Hz, Jcis = 10.3 Hz), 4.98–4.78 (m,
᎐
2
8H, ArCH2), 4.70, 4.69 (2d, 1H, β-H-1, 3J1,2 = 8.1Hz), 4.36–4.22
(m, 1H, OCHCH3), 4.09–4.02 (m, 1H, H-3), 3.97–3.92 (m, 1H,
H-3Ј), 3.87–3.64 (m, 11H, H-4Ј, -4, -5Ј, -5, H2-6, -6Ј, ArOCH3),
3.32 (dd, 1H, H-2Ј, 3J1Ј,2Ј = 3.8 Hz), 1.27, 1.18 (2d, 3H, CH3CH,
3J = 6.5 Hz), 1.09 (s, 9H, C(Me)3); 13C NMR (500 MHz; CDCl3)
3
3
3
0.5H, CH᎐CH , Jtrans = 17.0 Hz, Jcis = 10.5 Hz, J = 6.0 Hz),
᎐
2
5.49–5.36 (m, 4.5H, CH᎐CH , CH᎐CH , H-1Ј, -2Љ), 5.28–5.24
᎐
᎐
2
2
(m, 1H, H-2), 5.28–4.33 (m, 12H, ArCH2, H-1Љβ, -1β), 4.19–
4.07 (m, 2H, OCH, H-4Љ), 3.92–3.30 (m, 14H, H-3, -4, -5, H2-6,
H-3Ј, -4Ј, H-5Ј, H2-6Ј, H-3Љ, -5Љ, H2-6), 3.08 (dd, 1H, H-2Ј,
δ 170.3 (CO), 135.3, 134.1 (᎐CH), 129.2–121.6 (Ar-CH), 108.7
᎐
C
3
(Ar-CH, PMB), 110.2, 109.1 (᎐CH ), 93.0, 91.8 (C-1), 90.9 (α-
3J1,2 = 4 Hz), 1.13, 1.05 (2d, 3H, CH3CH, J = 6.5 Hz), 1.01 (s,
᎐
2
C-1Ј), 70.6, 69.1 (CH3CH), 75.2, 66.2 (C-3), 73.3 (C-3Ј), 71.2,
68.8, 65.5, 62.7, 55.8, 55.7, 48.9 (C-4, -5, -4Ј, -5Ј, ArCH2,
OCH3), 69.5, 69.0, 67.8 (C-6, -6Ј) 68.9 (C-2), 57.0 (C-2Ј), 27.0,
26.9 (C(Me)3), 20.0 (C(Me)3), 14.8, 13.9 (CHCH3) (Calc. for
C68H75N3O12Si: C, 70.75; H, 6.55; N, 3.64. Found: C, 71.02; H,
6.43; N, 3.48%).
9H, CMe3); 13C NMR (300 MHz; CDCl3) δC 165.6, 165.5, 165.0
(C᎐O), 140.3, 139.3 (CH᎐CH ), 138.8–132.8 (Ar-C), 130.3–
᎐
᎐
2
127.5 (Ar-CH), 116.9, 115.0 (CH᎐CH ), 100.4, 99.9, 98.6, 97.4
᎐
2
(C-1, -1Ј, -1Љ), 84.2, 80.6, 76.2, 75.7, 74.8, 74.7, 74.5, 74.4, 74.2,
74.0, 72.6, 72.5, 72.4 (C-2, -3, -4, -5, -2Ј, -3Ј, -4Ј, -5Ј, -2Љ, -3Љ, -4Љ,
-5Љ, OCH), 75.9, 74.4, 73.1, 70.1, 68.8, 68.7, 61.3 (ArCH2, C-6,
-6Љ, -6Љ), 27.4 (CMe3), 22.0, 20.6 (CHCH3), 19.8 (CMe3) (Calc.
for C94H97N3O18Si: C, 71.24; H, 6.17; N, 2.65. Found: C, 71.09;
H, 6.37; N, 2.41%).
(R/S)-But-3-en-2-yl 4-O-(2-azido-3-O-benzyl-6-O-tert-butyl-
diphenylsilyl-2-deoxy-ꢁ-D-glucopyranosyl)-2-O-benzoyl-3,6-di-
O-benzyl-ꢀ-D-glucopyranoside 19
(R/S)-Isobutyl 4-O-[2-acetamido-2-deoxy-6-O-tert-butyl-
diphenylsilyl-4-O-(ꢀ-D-glucopyranosyl)-ꢁ-D-glucopyranosyl]-ꢀ-
D-glucopyranoside 21
Compound 18 (98.8 mg, 0.086 mmol) was dissolved in DCM
(25 ml) and TFA (500 µl) and water (10 µl) were added drop-
wise. After stirring of the mixture for 1.5 h, TLC analysis
showed complete consumption of the starting material. The
reaction mixture was diluted with toluene (50 ml) and concen-
trated in vacuo. The residue was purified by flash silica gel
column chromatography (eluent 20% ethyl acetate in hexanes)
to give compound 19 (85.6 mg, 99.5%) as a clear oil, Rf 0.26
Compound 20 (200 mg, 0.13 mmol) was dissolved in methanol
(10 ml) saturated with K2CO3. After stirring of the mixture
for 48 h, TLC analysis showed complete consumption of the
starting material. The reaction mixture was filtered, neutral-
ized with Dowex Hϩ, filtered, and concentrated in vacuo. The
residue was dissolved in pyridine (2 ml) and cooled (0 ЊC).
Thioacetic acid (2 ml) was added dropwise and the mixture
was stirred at 0 Њ C for 18 h before being evaporated in vacuo,
and the residue was purified by silica gel chromatography
(eluent 0→1% methanol in DCM) to give the reduced trisac-
charide (99.2 mg, 59%). The trisaccharide was subjected to
catalytic hydrogenation in ethanol (25 ml) with Pd(OAc)2 (5
mg) as catalyst. After 48 h the reaction mixture was filtered
1
(20% ethyl acetate in hexanes); H NMR (500 MHz; CDCl3)
δ 8.04–8.02 (m, 2H, o-ArH, Bz), 7.61–7.14 (m, 28H, ArH),
3
3
5.85 (ddd, 0.5H, CH᎐CH , Jtrans = 16.5 Hz, Jcis = 11 Hz,
᎐
2
3J = 6.5 Hz), 5.48 (ddd, 0.5H, CH᎐CH , Jtrans = 17.5 Hz,
3
᎐
2
3Jcis = 10.5 Hz, J = 7.0 Hz), 5.55, 5.54 (2d, 1H, H-1Ј, J1Ј,2Ј = 5
3
3
Hz), 5.32–5.28 (m, 1H, H-2), 5.15–4.97 (m, 2H, CH᎐CH ),
᎐
2
4.83–4.82 (m, 1H, H-1), 4.74–4.43 (m, 6H, ArCH2), 4.25–4.14
(m, 1H, OCH), 3.98–3.93 (m, 1H, H-3), 3.79–3.57 (m, 9H,
H-3Ј, -4Ј, -4, -5Ј, -5, H2-6, -6Ј), 3.15–3.12 (m, 1H, H-2Ј), 2.42,
1
and evaporated to give pure 21 (49.3 mg, 76.3%), H NMR
3
3
2.22 (2d, 1H, 4Ј-OH, J = 4.5 Hz, J = 4.0 Hz), 1.19, 1.10 (2d,
(500 MHz; CD3OD) δ 7.73–7.36 (m, 10H, ArH), 5.32–5.29
3
3
3H, CH3CH, J = 6.5 Hz), 1.00 (s, 9H, CMe3); 13C NMR (300
(2d, 1H, H-1Јα, J = 3.5 Hz), 4.71–4.65, 4.34–4.16 (2m, 2H,
MHz: CDCl3) δC 165.3 (CO, benzoyl), 140.2, 139.3 (᎐CH),
H-1β, -1Љβ), 4.14–3.18 (m, 19H, H-2, -3, -4, -5, H2-6, H-2Ј,
-3Ј, -4Ј, -5Ј, H2-6, H-2Љ, H-3Љ, H-4Љ, H-5Љ, H2-6Љ, OCH), 1.84–
0.94 (m, 20H, CMe3, Ac, CHCH3, CH2CH3, CH2CH3); 13C
NMR (600 MHz; MeOH) δC 168.5 (CO), 129.1–120.4 (Ar-C),
96.4, 96.1 (C-1, -1Љ), 92.5 (C-1Ј), 71.2, 70.7, 70.6, 70.4, 70.2,
70.0, 69.5, 69.6, 69.0, 68.8, 68.6, 67.4, 67.0, 65.5, 63.3, 62.7
(C-2, -3, -4, -5, -6, -2Ј, -3Ј, -4Ј, -5Ј, -6Ј, -2Љ, -3Љ, -4Љ, -5Љ, -6Љ),
20.4 (CMe3), 20.2, 19.5 (CHCH3), 18.5 (CMe3), 14.5
(COCH3); FAB MS m/z 862.39 [M ϩ Na]ϩ.
᎐
138.4–133.0 (Ar-C), 130.1–127.7 (Ar-CH), 116.8, 115.1
(᎐CH ), 99.8, 98.4 (C-1β), 97.5 (C-1Јα), 83.9, 79.8, 75.7, 75.4,
᎐
2
75.1, 74.9, 74.5, 74.2, 74.0, 73.6, 73.2, 73.1, 72.5, 71.9, 69.6,
69.5, 64.0, 62.9 (C-2, -3, -4, -5, -6, -2Ј, -3Ј, -4Ј, -5Ј, -6Ј, CH3-
CH, ArCH2) 27.2 (CMe3), 21.9, 20.5 (CHCH3), 19.5 (CMe3)
(Calc. for C60H67N3O11Si: C, 69.68; H, 6.53; N, 4.06. Found: C,
69.78; H, 6.79; N, 3.74%).
(R/S)-But-3-en-2-yl 4-O-[2-azido-3-O-benzyl-6-O-tert-butyl-
diphenylsilyl-2-deoxy-4-O-(2,4-di-O-benzoyl-3,6-di-O-benzyl-ꢀ-
D-glucopyranosyl)-ꢁ-D-glucopyranosyl]-2-O-benzoyl-3,6-di-O-
benzyl-ꢀ-D-glucopyranoside 20
(R/S)-Isobutyl 4-O-[2-acetamido-6-O-tert-butyldiphenylsilyl-2-
deoxy-4-O-(ꢀ-D-glucopyranosyluronic acid)-ꢁ-D-glucopyrano-
syl]-ꢀ-D-glucuronic acid disodium salt 22
Compound 19 (188.2 mg, 0.18 mmol) was dissolved in DCM
Compound 21 (24.0 mg, 0.03 mmol), TEMPO (0.4 mg, 0.003
820
J. Chem. Soc., Perkin Trans. 1, 2001, 814–822