128
B. Fraser-Reid et al.
concentrated under reduced pressure. The residue was then purified by
flash column chromatography
4.90–4.55, m, 12H, BnCH2; 5.60, d, J 1.6 Hz, 1H, H1; 5.78, dd, J 2.0,
1.6, Hz, 1H; 8.12–6.84, m, 45H, ArH. 13C NMR (CDCl3, 100 MHz) δ
19.3, 26.8, 62.4, 66.4, 69.3, 71.5, 72.1, 72.6, 74.1, 74.92, 74.93, 75.5,
75.8, 78.4, 79.5, 80.6, 81.1, 81.3, 98.3 (C1), 127.1, 127.5, 127.6, 127.9,
127.96, 128.03, 128.2, 128.3, 128.4, 128.5, 128.6, 129.4, 130.0, 132.9,
133.3, 133.8, 135.6, 135.9, 137.2, 137.9, 138.3, 138.5, 139.1, 165.7
(C=O, Ph).
Acylation
To a solution of the product (0.057 mmol) in pyridine (2 mL) at 0°C was
added the acylating agent (0.22 mmol) and 4-dimethylaminopyridine
(DMAP) (7 mg, 0.057 mmol). The solution was stirred at room
temperature until completion (monitored by TLC), was quenched with
drops of water, and solvent was evaporated under vacuum. The residue
was then purified by flash column chromatography.
Acetylation of (23a) according to the general conditions and
purification by flash column chromatography (1:4 EtOAc/hexane)
afforded the acetate (23b) (57 mg, 79%) as a colourless gum (Found: C,
74.7; H, 6.6%; [M–1]+ (FAB), 1265.56. C79H82O13Si requires C, 74.9;
1
H, 6.5%; [M]+ 1267.61). H NMR (CDCl3, 400 MHz) δ 1.05, s, 9H;
1,3,4,5-Tetra-O-benzyl-2-O-(2,3,4-tri-O-benzyl-6-O-[t-butyl-
diphenylsilyl]-α-D-mannopyranosyl)-D-myo-inositol (20a) and
1,3,4,5-Tetra-O-benzyl-6-O-(2,3,4-tri-O-benzyl-6-O-[t-butyl-
diphenylsilyl]-α-D-mannopyranosyl)-D-myo-inositol (21a)
2.10, s, 3H; 3.31, dd, J 9.6, 9.6 Hz, 1H; 3.44, dd, J 3.2, 2.8 Hz, 1H; 3.46,
dd, J 3.2, 3.2 Hz, 1H; 3.61–3.52, m, 2H; 3.83, dd, J 9.6, 9.6 Hz, 1H;
4.07–3.96, m, 3H; 4.14, dd, J 10.0, 9.6 Hz, 1H; 4.47–4.01, m, 12H,
BnCH2; 5.60, d, J 1.2 Hz, 1H, H1; 5.80, dd, J 2.0, 1.6 Hz, 1H; 5.84, dd,
J 2.8, 2.4 Hz, 1H; 8.12–6.83, m, 45H, ArH. 13C NMR (CDCl3, 100
MHz) δ 19.3, 21.0, 26.8, 62.6, 65.9, 69.1, 71.4, 71.9, 72.2, 74.1, 74.7,
75.0, 75.8, 76.0, 78.1, 78.3, 78.7, 81.1, 81.7, 98.0 (C1), 127.1, 127.2,
127.4, 127.57, 127.60, 127.8, 128.0, 128.1, 128.2, 128.4, 128.5, 128.9,
129.3, 129.4, 130.0, 133.0, 133.4, 133.7, 135.7, 135.9, 136.8, 137.5,
137.7, 138.2, 138.5, 139.1, 166.0 (OCOPh), 170.4 (OCOCH3).
The diol (15) and glycosyl donor (19) were reacted under the general
glycosidation conditions. The crude residue obtained after workup was
purified by flash column chromatography (1:4 EtOAc/hexane) to
afford (20a) (44 mg, 49%) and (21a) (15 mg, 16%).
Data for (20a): (Found (FAB): [M–1]+, 1209.60. Calc. for
1
C77H82O11Si: [M]+, 1211.59). H NMR (CDCl3, 400 MHz) δ 1.02, s,
9H, But; 2.39, br s, 1H, OH; 3.18, dd, 1H; 3.32–3.25, m, 2H; 3.57, d,
1H; 3.79–3.71, m, 3H; 3.98–3.85, m, 3H; 4.26, dd, J 10.0, 9.6 Hz, 1H;
4.37, t, J 2.4 Hz, 1H; 4.95–4.41, m, 14H, Bn; 5.35, d, J 1.2 Hz, 1H, H1;
7.75–6.92, m, 45H, Ar. 13C NMR δ 19.3, 138.99, 26.8, 62.7, 70.1, 72.1,
72.2, 72.7, 72.9, 74.4, 75.2, 75.6, 75.8, 79.2, 79.4, 80.5, 80.9, 83.2, 98.0
(C1), 127.06, 127.11, 127.2, 127.3, 127.4, 127.5, 127.6, 127.7, 127.96,
128.02, 128.06, 128.13, 128.18, 128.22, 128.29, 128.34, 128.5, 128.6,
129.36, 129.42, 133.6, 133.9, 135.6, 136.1, 137.4, 137.7, 138.6, 138.7.
Benzoylation of (20a) under standard conditions and flash
chromatography (1:4 EtOAc/hexane) of the crude residue afforded the
corresponding benzoate (20b) (31 mg, 94%) as a colourless gum
(Found (FAB): [M–1]+, 1209.59. Calc. for C77H82O11Si: [M]+,
1211.59). 1H NMR (CDCl3, 400 MHz) δ 1.03, s, 9H; 3.30, dd, J 10.0,
2.3 Hz, 1H; 3.42, dd, J 10.0, 2.0 Hz, 1H; 3.60–3.51, m, 2H; 4.27, dd, J
11.2, 2.8 Hz, 1H; 4.02–3.86, m, 4H; 4.27, dd, J 10.0, 10.0 Hz, 1H;
4.99–4.41, m, 15H; 5.40, br s, 1H; 5.76, dd, J 10.0, 9.6 Hz, 1H;
8.17–6.95, m, Ar.
1,3,4,5-Tetra-O-benzyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-D-gluco-
pyranosyl)-D-myo-inositol (27a)
The diol (15) and glycosyl donor (25) were reacted under general
conditions for 3 min. Workup and purification by flash column
chromatography (3:7 EtOAc/hexane) afforded (27a) (78 mg, 76%) as a
colourless gum (Found (FAB): [M+1]+, 1119.6. Calc. for C68H62O15:
[M+1]+, 1119.24). 1H NMR (CDCl3, 400 MHz) δ 2.46, s, 1H, OH;
3.33–3.27, m, 3H; 4.10–3.96, m, 2H; 4.72–4.37, m, 10H; 4.93, 2 ´ d,
2H, Bn; 5.48, d, J 8.4 Hz, 1H, H1; 5.54, dd, J 10.0, 8.0 Hz, 1H; 5.64, dd,
J 10.0, 9.6 Hz, 1H; 5.85, dd, J 10.0, 9.6 Hz, 1H; 8.00–7.17, m, 40H,
ArH. 13C NMR (CDCl3, 100 MHz) δ 63.2. 68.7, 70.0, 72.0, 72.37,
72.44, 73.0, 73.4, 75.3, 75.7, 78.6, 79.1, 81.1, 83.2, 100.6 (C1), 127.58,
127.63, 127.7, 127.8, 127.9, 128.27, 128.32, 128.6, 128.8, 129.7, 129.8,
133.10, 133.11, 133.4, 137.8, 138.3, 138.5, 165.2, 165.7, 166.1.
Acetylation of (27a) under general conditions afforded the acetate
(27b) (21 mg, 82%) as a colourless gum. 1H NMR (CDCl3, 400 MHz)
δ 2.02, s, 3H; 3.39–3.33, m, 3H; 3.78, dd, J 9.6, 9.6 Hz, 1H; 3.93–3.88,
m, 1H; 4.30, dd, J 9.6, 9.2 Hz, 1H; 4.85–4.36, m, 10H; 5.44, d, J 7.6 Hz,
1H, H1; 5.58, dd, J 9.6, 8.0 Hz, 1H; 5.65, dd, J 9.6, 9.6 Hz, 1H; 5.73,
dd, J 2.8, 2.8 Hz, 1H; 5.83, dd, J 10.0, 9.6 Hz, 1H; 7.96–7.15, m, 40H,
ArH.
Data for (21a). 1H NMR (CDCl3, 400 MHz) δ 1.03, s, 9H; 3.30, dd,
J 10.0, 2.3 Hz, 1H; 3.42, dd, J 10.0, 2.0 Hz, 1H; 3.60–3.51, m, 2H; 4.27,
dd, J 11.2, 2.8 Hz, 1H; 4.02–3.86, m, 4H; 4.27, t, 1H; 4.99–4.41, m,
15H; 5.40, br s, 1H; 5.76, dd, J 10.0, 9.6 Hz, 1H; 8.17–6.95, m, Ar.
Acetylation of (21a) under the general conditions afforded the
corresponding acetate (21b) (6 mg, 59%) as a colourless gum (Found
(FAB): [M–1]+, 1251.56. Calc. for C79H84O12Si: [M]+, 1253.63). 1H
NMR (CDCl3, 400 MHz) δ 0.99, s, 9H; 2.12, s, 3H; 3.28, dd, J 9.6, 9.6
Hz, 1H; 3.37, dd, J 9.6, 2.4 Hz, 1H; 3.44, dd, J 10.0, 2.8 Hz, 1H;
3.59–3.57, m, 2H; 3.92–3.76, m, 4H; 4.06, dd, J 10.0, 9.6 Hz, 1H; 4.18,
dd, J 10.0, 10.0 Hz, 1H; 4.91–4.32, m, 14H; 5.49, d, J 1.2 Hz, 1H; 5.84,
dd, J 2.8, 2.4 Hz,1H; 7.71–6.88, m, Ar.
1,3,4,5-Tetra-O-benzyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-D-galacto-
pyranosyl)-D-myo-inositol (28a)
The diol (15) and glycosyl donor (26) were reacted under general
conditions. Workup and flash column chromatography (3:7
EtOAc/hexane) afforded (28a) (73%) as a colourless gum (Found
(FAB): [M–1]+, 1117.3; [M+1]+, 1119.3. Calc. for C68H62O15:
[M+1]+, 1119.24). 1H NMR (CDCl3, 400 MHz) δ 2.48, br s, 1H;
3.37–3.32, m, 3H; 4.00, dd, J 9.6, 9.6 Hz, 1H; 4.23–4.17, m, 2H;
4.91–4.39, m, 10H; 5.16, d, J 11.2 Hz, 1H; 5.56, d, J 8.0 Hz, 1H, H1;
5.57, dd, J 10.4, 3.2 Hz, 1H; 5.85, dd, J 10.4, 8.0, Hz, 1H; 5.96, dd, J
3.2, 0.4 Hz, 1H; 8.03–7.17, m, 40H, ArH. 13C NMR (CDCl3, 100 MHz)
δ 61.7. 68.2, 68.7, 70.5, 71.0, 71.7, 72.4, 73.4, 75.1, 75.7, 77.1, 78.1,
79.2, 81.1, 83.2, 100.7 (C1), 127.3, 127.5, 127.6, 127.7, 127.8, 127.87,
127.89, 128.2, 128.3, 128.4, 128.5, 128.6, 129.6, 129.7, 129.8, 133.1,
133.2, 133.3, 137.8, 138.3, 138.5, 138.6, 165.3, 165.4, 165.5, 165.9.
Acetylation of (28a) under general conditions followed by flash
column chromatography (1:3 EtOAc/hexane) afforded the acetate
(28b) in 96% yield (Found (FAB): [M–1]+, 1159.2; [M+1]+, 1161.2.
Calc. for C70H64O16: [M+1]+, 1161.28). 1H NMR (CDCl3, 400 MHz) δ
2.07, s, 3H; 3.44–3.37, m, 3H; 3.82, dd, J 9.6, 9.6 Hz, 1H; 4.14, dd, J
7.2, 6.0 Hz, 1H; 4.90–4.32, m, 11H; 5.44, d, J 8.0 Hz, 1H; 5.57, dd, J
10.8, 3.6 Hz, 1H; 5.79, dd, J 2.8, 2.8 Hz, 1H; 5.88, dd, J 10.4 8.0, Hz,
1H; 5.96, dd, J 3.6, 0.4 Hz, 1H; 8.02–7.16, m, 40H, ArH.
1,3,4,5-Tetra-O-benzyl-6-O-(2-O-benzoyl-3,4-di-O-benzyl-6-O-[t-
butyldiphenylsilyl]-α-D-mannopyranosyl)-D-myo-inositol (23a)
Reaction with NPOE (22) as Donor
The diol (15) and glycosyl donor (22) were reacted under standard
conditions for 20 min. Standard workup, and flash column
chromatography of the crude residue (1:4 EtOAc/hexane) afforded
(23a) (80 mg, 71%) as a colourless gum.
Reaction with NPGAC (24) as Donor
The diol (15) and 2-benzoyl n-pentenyl glycoside (24) were reacted
under standard conditions. Standard workup and flash column
chromatography (1:4 EtOAc/hexane) afforded (23a) (65 mg, 58%) as a
colourless gum. 1H NMR (CDCl3, 400 MHz) δ 1.06, s, 9H; 2.36, br s,
1H, OH; 3.27, dd, J 9.6, 9.2 Hz, 1H; 3.34, dd, J 3.2, 3.2 Hz, 1H; 3.37,
dd, J 3.2, 2.8 Hz, 1H; 3.58–3.48, m, 2H; 3.98–3.91, m, 2H; 4.05, dd, J
10.0, 3.2 Hz, 1H; 4.17–4.12, m, 2H; 4.22, dd, J 10.0, 9.6 Hz, 1H;