of methanol, concentrated, extracted with DCM, and the
m, 1 H, H-5), 3.54 (t, 1 H, J5Ј,6Јa ≈ J6Јa,6Јb ≈ 9.4, H-6Јa), 3.51 (s,
extract chromatographed on silica with pentane–ethyl acetate
(8 : 2) to give 41 (372 mg, 91%), [α]D ϩ33.4 (c 0.5, CHCl3); H
3 H, OMe), 3.41–3.30 (m, 2 H, H-2, H-6b), 3.27 (dd, 1 H, J5Ј,6Јb
3.7, H-6Јb), 2.03 (br s, 1 H, OH), 1.53 (br s, 2 H, OH) (Found:
C, 68.5; H, 6.8. Calc. for C41H48O11: C, 68.7; H, 6.75%).
1
NMR (CDCl3) δH 7.33–7.15 (m, 40 H, arom), 5.02 (d, 1 H, J1Ј,2Ј
2.4, H-1Ј), 4.90 (d, 1 H, 2J 11.1, CH2Ph), 4.86 (d, 1 H, 2J 11.4,
2
CH2Ph), 4.75 (d, 1 H, J 11.8, CH2Ph), 4.73 (s, 2 H, CH2Ph),
Methyl 2,3-di-O-acetyl-4-O-(2,3,4,6-tetra-O-benzyl-ꢁ-D-
galactopyranosyl)-ꢀ-D-galactopyranoside 45
2
2
4.66 (d, 1 H, J 11.8, CH2Ph), 4.53 (d, 1 H, J 11.4, CH2Ph),
2
4.53 (d, 1 H, J 11.1, CH2Ph), 4.42–4.31 (m, 3 H, H-5, CH2),
4.26 (d, 1 H, 2J 11.8, CH2Ph), 4.21 (d, 1 H,2J 11.8, CH2Ph), 4.15
(s, 2 H, CH2Ph), 4.11–3.88 (m, 8 H, H-1, H-4, H-6a, H-2Ј, H-3Ј,
H-4Ј, CH2), 3.56–3.40 (m, 7 H, H-2, H-5, H-6b, H-6Јa, H-6Јb,
Me), 3.28–3.24 (m, 2 H, H-3, H-6Јb) (Found: C, 70.7; H, 6.3.
Calc. for C69H73O15P: C, 70.6; H, 6.3%).
A solution of 44 (1.723 g, 2.4 mmol) and t-BuMe2SiCl (0.55 g,
3.65 mmol) in pyridine (15 mL) was stirred for 3 h, then Ac2O
(3 mL) was added. After 2 days the reaction mixture was
quenched by the addition of methanol, concentrated, and co-
evaporated with toluene. A solution of the residue in 80% aq.
acetic acid (20 mL) was stored for 1 h at 60 ЊC, then was concen-
trated, and chromatographed on silica gel with pentane–ethyl
acetate (7 : 3 to 1 : 1) to give 45 (1.364 g, 70%), [α]D ϩ31.4 (c 0.5,
CHCl3); 1H NMR (CDCl3) δH 7.38–7.26 (m, 20 H, arom), 5.19
(dd, 1 H, J1,2 7.8, J2,3 10.7, H-2), 4.90 (d, 1 H, 2J 11.7, CH2Ph),
4.89 (d, 1 H, 2J 11.1, CH2Ph), 4.82 (dd, 1 H, J3,4 2.9, H-3), 4.78–
4.46 (m, 6 H, CH2Ph), 4.60 (d, 1 H, J1Ј,2Ј 1.9, H-1Ј), 4.34 (d, 1 H,
H-1), 4.29 (br dd, 1 H, J5Ј,6Јa 9.0, J6Јa,6Јb 3.3, H-6Јa), 4.17 (d, 1 H,
H-4), 4.14 (br s, 1 H, H-4Ј), 4.04 (m, 2 H, H-2Ј, H-3Ј), 3.80–3.55
(m, 6 H, H-5, H-6a, H-6b, H-5Ј, H-6Јb, OH), 4.18 (s, 3 H,
OMe), 2.04 and 1.93 (2 s, 6 H, 2Ac) (Found: C, 67.5; H, 6.4.
Calc. for C45H52O13: C, 67.5; H, 6.5%).
Methyl 4-O-(ꢁ-D-galactopyranosyl)-2-O-(2-phosphonyloxy-
ethyl)-ꢀ-D-galactopyranoside disodium salt 8
To a solution of 41 (345 mg, 0.294 mmol) in EtOH (5 mL) was
added Pd/C (10%; 50 mg). The mixture was stirred overnight
under a flow of H2. Then PtO2 (20 mg) was added and hydro-
genation was continued for 5 h. The catalyst was filtered off, the
supernatant was concentrated and the residue was chromato-
graphed on IATROBEADS with DCM–MeOH–water (800 :
200 : 0 to 700 : 300 : 5). The product was dissolved in water and
passed through Dowex 50W (Naϩ) to give 8 (87.8 mg, 96%),
1
[α]D ϩ74.9 (c 0.6, H2O); H NMR (D2O) δH 4.96 (d, 1 H, J1Ј,2Ј
4.0, H-1Ј), 4.45 (d, 1 H, J1,2 7.6, H-1), 4.37 (t, 1 H, J5Ј,6Јa
≈
Methyl 2,3-di-O-acetyl-4-O-(2,3,4,6-tetra-O-benzyl-ꢁ-D-
J5Ј,6Јb ≈ 6.2, H-5Ј), 4.07–4.03 (m, 3 H, H-4, H-4Ј, CH2), 4.00–
3.97 (m, 2 H, CH2), 3.94–3.81 (m, 5 H, H-6a, H-6b, H-2Ј, H-3Ј,
CH2), 3.79 (dd, 1 H, J2,3 10.1, J3,4 3.0, H-3), 3.74 (dd, 1 H,
J5,6a 5.0, J5,6b 7.5, H-5), 3.70 (d, 2 H, H-6Јa, H-6Јb), 3.60 (s, 3 H,
Me), 3.40 (dd, 1 H, H-2); m/z (EI) 503.1145 [(MH2 Ϫ Na)ϩ.
C15H29NaO15P requires m/z, 503.1142].
galactopyranosyl)-6-O-(p-tolylsulfonyl)-ꢀ-D-galactopyranoside
46
To a solution of 45 (2.62 g, 3.27 mmol) in pyridine (20 mL) was
added TsCl (1.87 g, 9.8 mmol). After 2 days of stirring at room
temperature the mixture was diluted with DCM, washed suc-
cessively with water, 1 M HCl, water, and aq. NaHCO3, and the
extract was concentrated, and chromatographed on the silica
gel with pentane–ethyl acetate (4 : 1 to 3 : 2) to give 46 (2.07 g,
Methyl 2,3,6-tri-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzyl-ꢁ-D-
galactopyranosyl)-ꢀ-D-galactopyranoside 43
1
66%), [α]D ϩ40.6 (c 1.5, CHCl3); H NMR (CDCl3) δH 7.67–
A mixture of methyl 2,3,6-tri-O-benzoyl-β--galactopyrano-
side13 42 (5.2 g, 10.2 mmol), 168 (6.3 g, 10.77 mmol), and mol.
sieves (4 Å, 10 g) in DCM (50 mL) was stirred for 1 h under an
argon atmosphere. The mixture was cooled at Ϫ15 ЊC, and a
mixture of NIS (2.35 mg, 10.44 mmol) and AgOTf (378 mg,
1.47 mmol) was added in 3 portions. The precipitate was filtered
off, and the solution was washed successively with aq. Na2S2O3
and water, and concentrated. Chromatography of the residue
on silica gel in pentane–ethyl acetate (6 : 1 to 4 : 1) gave 43 (10.18
g, 95%), [α]D ϩ57.1 (c 0.7; CHCl3); 1H NMR (CDCl3) δH 8.00–
7.88 (m, 6 H, arom), 7.45–7.11 (m, 29 H, arom), 5.77 (dd, 1 H,
J1,2 7.7, J2,3 10.6, H-2), 5.22 (dd, 1 H, J3,4 2.9, H-3), 4.91 (d, 1 H,
J1Ј,2Ј 3.4, H-1Ј), 4.85–4.67 (m, 7 H, CH2Ph), 4.61 (d, 1 H, H-1),
4.44 (d, 1 H, 2J 11.1, CH2Ph), 4.39 (d, 1 H, H-4), 4.32 (dd, 1 H,
J5,6a 5.0, J5,6b 9.4, H-5), 4.16 (dd, 1 H, J2Ј,3Ј 10.3, J3Ј,4Ј 2.5, H-3Ј),
4.15 (br s, 1 H, H-4Ј), 4.10–4.00 (m, 4 H, H-2Ј, H-6a, H-6b,
H-6Јa), 3.53 (m, 3 H, OMe), 3.35 (t, 1 H, J5Ј,6Јa ≈ J5Ј,6Јb ≈ 9.0,
H-5Ј), 2.87 (dd, 1 H, J6Јa,6Јb 4.9, H-6Јb) (Found: C, 72.4; H, 5.8.
Calc. for C62H60O14: C, 72.4; H, 5.9%).
7.64 (m, 2 H, arom), 7.35–7.20 (m, 22 H, arom), 5.19 (dd, 1 H,
J1,2 7.7, J2,3 10.5, H-2), 4.88 (d, 1 H, 2J 11.2, CH2Ph), 4.82 (dd,
3
1 H, J3,4 3.0, H-3), 4.73 (d, 1 H, J 12.1, CH2Ph), 4.70 (s, 2 H,
3
CH2Ph), 4.65 (br s, 1 H, H-1Ј), 4.59 (d, 1 H, J 12.1, CH2Ph),
4.53 (d, 1 H, 3J 11.2, CH2Ph), 4.47 (dd, 1 H, J5,6a 5.7, J6a,6b 11.0,
H-6a), 4.43 (s, 2 H, CH2Ph), 4.33 (d, 1 H, H-1), 4.29 (dd, 1 H,
J5,6b 6.8, H-6b), 4.23 (dd, 1 H, J6Јa,6Јb 5.4, J5Ј,6Јa 8.7, H-6Јa), 4.07
(br s, 1 H, H-4Ј), 4.04 (br d, 1 H, H-4), 3.95 (m, 2 H, H-2Ј, H-3Ј),
3.80 (br t, 1 H, H-5), 3.61 (t, 1 H, J5Ј,6Јa ≈ J5Ј,6Јb ≈ 8.8, H-5Ј), 3.45
(s, 3 H, OMe), 3.45 (dd, 1 H, H-6Јb), 2.35 (s, 3 H, ArMe), 2.05
and 2.04 (2 s, 6 H, Ac) (Found: C, 65.4; H, 6.15; S, 3.1. Calc. for
C52H58O15S: C, 65.4; H, 6.1; S, 3.4%).
Methyl 2,3-di-O-acetyl-6-azido-6-deoxy-4-O-(2,3,4,6-tetra-O-
benzyl-ꢁ-D-galactopyranosyl)-ꢀ-D-galactopyranoside 47
A suspension of NaN3 (3.57 mg, 55 mmol) in a solution of 46
(1.052 g, 1.1 mmol) and Bu4NI (50 mg) in DMF (5 mL) was
stirred for 24 h at 110 ЊC. The mixture was diluted with water,
extracted with DCM, and the organic layer was concentrated.
Chromatography of the residue on silica gel with pentane–ethyl
acetate (2 : 1) afforded 47 (595 mg, 65%), [α]D ϩ57.2 (c 0.7,
Methyl 4-O-(2,3,4,6-tetra-O-benzyl-ꢁ-D-galactopyranosyl)-ꢀ-D-
galactopyranoside 44
1
CHCl3); H NMR (CDCl3) δH 7.4–7.24 (m, 20 H, arom), 5.22
A solution of 43 (2.89 g, 2.8 mmol) in methanol (40 mL) was
refluxed for 5 h in the presence of MeONa (300 mg), then neu-
tralized with Dowex 50W (Hϩ) and concentrated. Chroma-
tography of the residue on silica gel in DCM–MeOH (20 : 1)
(dd, 1 H, J1,2 7.8, J2,3 10.6, H-2), 4.94–4.88 (m, 2 H, CH2Ph),
4.81 (dd, 1 H, J3,4 2.9, H-3), 4.79 (d, 1 H, 2J 13, CH2Ph), 4.75 (d,
1 H, 2J 13.0, CH2Ph), 4.69 (d, 1 H, J1Ј,2Ј ≈ 1, H-1Ј), 4.60 (d, 1 H,
2
3J 11.5, CH2Ph), 4.58 (d, 1 H, J 11.2, CH2Ph), 4.46 (s, 2 H,
1
gave 44 (1.96 g, 97%), [α]D Ϫ7.8 (c 0.3, CHCl3); H NMR
CH2Ph), 4.36 (d, 1 H, H-1), 4.27 (br dd, 1 H, J5Ј,6Јa 8.2, J6Јa,6Јb
5.7, H-6Јa), 4.13 (broad s, 1 H, H-4Ј), 4.03 (m, 2 H, H-2Ј, H-3Ј),
3.95 (d, 1 H, H-4), 3.71 (dd, 1 H, J6a,6b 12.6, J5,6a 8.1, H-6a),
3.68–3.60 (m, 2 H, H-5, H-5Ј), 3.51 (s, 3 H, OMe), 3.47 (dd,
1 H, J5Ј,6Јb 8.0, H-6Јb), 3.14 (dd, 1 H, J5,6b 4.0, H-6b), 2.05 and
2.02 (2 s, 6 H, Ac) (Found: C, 65.20; H, 6.31; N, 4.72. Calc. for
C45H51N3O12: C, 65.44; H, 6.22; N, 5.09%).
3
(CDCl3) δH 7.37–7.25 (m, 20 H, arom), 4.90 (d, 2 H, J 11.7,
CH2Ph), 4.80 (d, 1 H, J1Ј,2Ј 3.7, H-1Ј), 4.74 (s, 2 H, CH2Ph), 4.67
3
(d, 1 H, CH2Ph), 4.52 (d, 1 H, CH2Ph), 4.42 (d, 1 H, J 11.3,
CH2Ph), 4.35 (d, 1 H, CH2Ph), 4.14–4.07 (m, 3 H, H-1, H-2Ј,
H-5Ј), 3.99 (dd, 1 H, J3Ј,4Ј 2.6, J2Ј,3Ј 10.1, H-3Ј), 3.93–3.96 (m,
3 H, H-3, H-4, H-4Ј), 3.75–3.70 (br m, 1 H, H-6a), 3.66–3.62 (br
848
J. Chem. Soc., Perkin Trans. 1, 2001, 838–853