ARTICLE IN PRESS
8
T. Belz, S.J. Williams/Carbohydrate Research ■■ (2016) ■■–■■
(
4.58 mg, 67.3 μmol) at 35 °C with stirring for 1 h. The reaction
mixture was cooled to rt and acetic anhydride (1 ml) and pyridine
0.5 ml) were added and the solution was stirred at rt for 1 h. The
pressure. The residue was purified by flash chromatography (1:1→6:4
EtOAc/pet. spirits) to give iodide 10 (44.7 mg, 80%), mp 194–
2
3
(
197 °C, [α]
5.09 (16 H, m, H(1,2,3,4)
H, dd, J4,5 9.1, J5,6 2.2 Hz, H5 ), 3.27 (1 H, dd, J5,6 2.3, J6,6 10.9 Hz, H6 ),
3.15 (1 H, dd, J5,6 9.0, J6,6 10.9 Hz, H6 ), 3.06–2.94 (3 H, m, H6
D
+191.0 (c 0.5 in CHCl
3
). δ
H
3
(400 MHz, CDCl ) 5.36–
A,B,C,D
B,C,D
solvent was evaporated under reduced pressure with azeotropic
removal by co-evaporation with toluene. The resulting residue was
diluted with CH
), 4.34–4.31 (3 H, m, H5
), 4.17 (1
A
D
D
A,B,C
2
Cl
2
and washed sequentially with aq 0.1 M HCl, brine,
), evaporated to dryness under reduced pres-
),
A,B,C
and water, dried (MgSO
4
2.76–2.68 (3 H, m, H6 ), 2.17, 2.15, 2.13, 2.13, 2.13, 2.08, 2.07, 2.06,
sure and the residue purified by flash chromatography (4:6 → 6:4
EtOAc/pet. spirits) to give silyl thiomannoside 19 (27.4 mg, 75%), mp
3 C 3
1.98, 1.96, 1.95 (39 H, 11s, 12 × Ac, SCH ); δ (100 MHz, CDCl ) 170.1,
170.0, 169.94, 169.92, 169.83, 169.81, 169.78, 169.77, 169.7, 169.64,
2
3
A,B,C,D
9
5
1–94 °C, [α]
D
+146.3 (c 1.0 in CHCl
3
). δ
H
C,D
(700 MHz, CDCl
3
) 5.41–
169.55 (12 × C = O), 83.2, 81.3, 81.1, 80.6 (C1
), 71.03, 70.95, 70.81,
A
B
.27 (13 H, m, H(2,3,4) ,(1,2,3,4) ,(2,3,4) ), 5.16 (1 H, s, J1,2 1.3 Hz,
70.77, 70.7, 70.2, 69.4, 69.3, 69.19, 69.15, 69.1, 69.0, 68.94, 68.88, 68.8,
A
B,C,D
A,B,C,D
A,B,C
H1 ), 4.34–4.30 (3 H, m, H5
2
), 4.13 (1 H, ddd, J4,5 9.7, J5,6 4.2, J5,6
68.6 (C(2,3,4,5)
), 31.1, 30.5, 30.3 (C6 ), 21.1, 20.93, 20.90, 20.87,
A
D
D
.1 Hz, H5 ), 3.75 (1 H, dd, J5,6 4.3, J6,6 11.6 Hz, H6 ), 3.69 (1 H, dd,
20.8, 20.7, 20.62, 20.58 (36 H, 8s, 12 × Ac), 13.7 (SCH
HRMS (ESI ) calcd for C49
3
), 3.6 (C6 );
D
C
+
+
J5,6 1.9, J6,6 11.6 Hz, H6 ), 3.05 (1 H, dd, J5,6 2.4, J6,6 14.8 Hz, H6 ), 2.99
H
67
O
28
S
4
Na (M + Na) 1381.1639. Found
B
(1 H, dd, J5,6 2.2, J6,6 14.6 Hz, H6 ), 2.84 (1 H, dd, J5,6 2.4, J6,6 14.2 Hz,
1381.1664.
A
B,C
A
H6 ), 2.80–2.74 (2 H, m, H6 ), 2.70 (1 H, dd, J5,6 8.2, J6,6 14.2 Hz, H6 ),
2
1
.22, 2.18, 2.18, 2.18, 2.17, 2.11, 2.07, 2.05, 2.02, 2.00 (39 H, 10s,
2 × Ac, SCH ), 0.93 (9 H, s, C(CH ), 0.07, 0.06 (6 H, 2 s, Si(CH );
(100 MHz, CDCl
4.16. Methyl S-(2,3,4,6-tetra-O-acetyl-α-
S-(2,3,4-tri-O-acetyl-6-thio-α- -mannopyranosyl)-(1→6)-S-(2,3,4-
tri-O-acetyl-6-thio-α- -mannopyranosyl)-(1→6)-S-(2,3,4-tri-O-
acetyl-6-thio-α- -mannopyranosyl)-(1→6)-S-(2,3,4-tri-O-acetyl-6-
thio-α- -mannopyranosyl)-(1→6)-(2,3,4-tri-O-acetyl-1,6-dithio-α-
-mannopyranoside) (11)
D
-mannopyranosyl)-(1→6)-
3
3
)
3
3
)
2
D
δ
1
7
6
3
C
3
) 170.1, 170.0, 169.93, 169.88, 169.85, 169.84,
D
A,B,C,D
69.73, 169.69, 169.5 (12 × C = O), 83.2, 81.7, 81.3, 80.9 (C1
), 71.9,
D
1.3, 71.0, 70.85, 70.83, 69.6, 69.43, 69.40, 69.3, 69.25, 69.20, 69.1,
D
A,B,C
D
9.0, 68.89, 68.88, 66.6, 62.0 (C(2,3,4,5)
,(2,3,4,5,6) ), 31.4, 30.59,
D
A,B,C
0.57 (C6
), 25.8 ((CH
3
)
3
C), 20.92, 20.87, 20.8, 20.7, 20.65, 20.63
C), 13.6 (SCH ), −5.30, −5.62 (SiMe ); HRMS
SiNa (M + Na)+ 1385.3486. Found
(
(
12 × CH CO), 18.4 ((CH
ESI ) calcd for C55
3
)
3 3
3
2
(a) A solution of iodide 10 (45.0 mg, 32.9 μmol) and thioacetate
8 (35.0 mg, 49.4μmol) in DMF (0.25 ml) was treated with and
diethylamine (21 μL) with stirring at rt for 1 h. The solvent was
+
H
82
O
29
S
4
1
385.3515.
evaporated and the residue was dissolved in CH
layer was washed with 0.1 N HCl, water, dried (MgSO
2
Cl
2
. The organic
), evapo-
4
.15. Methyl S-(2,3,4-tri-O-acetyl-6-deoxy-6-iodo-α-
D
-
4
mannopyranosyl)-(1→6)-S-(2,3,4-tri-O-acetyl-6-thio-α-
mannopyranosyl)-(1→6)-S-(2,3,4-tri-O-acetyl-6-thio-α-
mannopyranosyl)-(1→6)-(2,3,4-tri-O-acetyl-1,6-dithio-α-
mannopyranoside) (10)
D
D
-
-
rated to dryness under reduced pressure and the residue was
purified by recrystallisation from EtOAc to give thiomannoside
2
3
D
-
11 (16 mg, 27%), mp 250–253 °C, [α]
D
3
+135.3 (c 0.5 in CHCl ).
A
B,C,D,E,F
δ
5
H
(700 MHz, CDCl
.16 (1 H, s, H1 ), 4.36–4.25 (7 H, m, H5
3
) 5.38–5.23 (15 H, m, H(1,2,3,4) ,(2,3,4)
),
A
A,B,C,D,E
F
,(5,6) ), 4.13 (1 H,
F
C,D,E
4.15.1. Methyl S-(2,3,4-tri-O-acetyl-α-
D
-mannopyranosyl)-(1→6)-S-
dd, J5,6 2.1, J6,6 12.3 Hz, H6 ), 3.10–3.01 (3 H, m, H6
H, m, H6 ), 2.82 (1 H, dd, J5,6 2.3, J6,6 14.3 Hz, H6 ), 2.80–2.66 (5
H, m, H6
), 2.97 (1
B
A
(
(
(
2,3,4-tri-O-acetyl-6-thio-α-
D
-mannopyranosyl)-(1→6)-S-
-mannopyranosyl)-(1→6)-
A,B,C,D,E
2,3,4-tri-O-acetyl-6-thio-α-
D
), 2.21, 2.20, 2.19, 2.18, 2.17, 2.13, 2.12, 2.08, 2.08,
); δ (100 MHz,
) 170.6, 170.2, 170.05, 170.03, 170.00, 169.90, 169.89,
2,3,4-tri-O-acetyl-1,6-dithio-α-
Silyl thiomannoside 19 (0.140 g, 0.104 mmol) was treated with
AcOH, H O, THF (3:1:1, 30 ml) with stirring at 40 °C overnight. The
D
-mannopyranoside)
2.03, 2.02, 2.01, 2.00, 1.99 (60 H, 14s, 19 × Ac, SCH
CDCl
3
C
3
2
169.88, 169.86, 169.8, 169.73, 169.72, 169.69, 169.69, 169.67,
solvent was evaporated under reduced pressure with co-evaporated
with additional water and the residue was purified by flash chro-
matography (7:3→9:1 EtOAc/pet. spirits) to give the title alcohol
169.6 (19 × C = O), 83.2, 81.5, 81.0, 80.39, 80.36, 80.2
A,B,C,D,E,F
(C1
), 71.05, 71.00, 70.8, 69.4, 69.3, 69.24, 69.22, 69.12,
69.10, 69.00, 68.97, 68.92, 68.90, 68.87, 68.7, 66.32, 62.28
2
3
A,B,C,D,E
F
A,B,C,D,E
(
(
5
90.3 mg, 70%), mp 88–91 °C, [α]
400 MHz, CDCl
D
+113.9 (c 0.5 in CHCl
3
). δ
H
(C(2,3,4,5)
,(2,3,4,5,6) ), 31.1, 30.32, 30.28, 30.0, 29.9 (C6
),
A
B
C,D
3
) 5.35–5.21 (13 H, m, H(2,3,4) ,(1,2,3,4) ,(2,3,4) ),
21.0, 20.92, 20.90, 20.87, 20.73, 20.69, 20.66, 20.6 (19 × CH
3
CO),
A
C
+
Na (M + Na)+
.12 (1 H, d, J1,2 1.3, H1 ), 4.32–4.27 (1 H, m, H5 ), 4.12–4.06 (1 H,
13.6 (SCH
3
); HRMS (ESI ) calcd for C75
H
102
O
44
S
6
D
D
m, H5 ), 3.64 (2 H, m, H(6,6) ), 2.98 (1 H, dd, J5,6 3.0, J6,6 14.0 Hz,
H6 ), 2.91 (1 H, dd, J5,6 3.0, J6,6 14.0 Hz, H6 ), 2.86 (1 H, dd, J5,6 3.0,
1921.3960. Found 1921.4060.
C
B
(b) A solution of thiomannoside 23 and triethylsilane (5.2 ml,
0.033 μmol) in DMF (0.5 ml) was treated with TFA (0.5 ml) and
stirred at rt for 90 min. The TFA was evaporated under a stream
A
A,B,C
J6,6 14.0 Hz, H6 ), 2.78–2.65 (3 H, m, H6 ), 2.29–2.31 (1 H, m, OH),
2
1
1
8
6
.17, 2.15, 2.14, 2.14, 2.08, 2.08, 2.07, 2.04, 1.99, 1.98 (36 H, 10s,
2 × Ac), 1.96 (3 H, SCH ); δ (100 MHz, CDCl ) 171.4, 170.9, 170.5,
3
C
3
3
of nitrogen. Et N (18 μl, 0.13 mmol) and MeI (2.61 μl, 0.042 mmol)
70.3, 170.1, 170.0, 169.9, 169.82, 169.76, 169.7 (C = O), 83.3, 82.0,
were added and the mixture stirred for 2 h. The solvent was
evaporated under reduced pressure and the residue was dis-
solved in EtOAc. The organic solution was washed with 0.1 N Hcl,
A,B,C,D
1.4, 81.1 (C1
), 71.64, 71.57, 71.2, 71.0, 70.8, 69.4, 69.4, 69.3, 69.2,
A,B,C
D
9.1, 69.0, 68.9, 66.1, 63.2 (C(2,3,4,5) ,(2,3,4,5,6) ), 31.5, 30.81, 30.79
A,B,C
(C6 ), 20.9, 20.85, 20.82, 20.75, 20.7, 20.6 (12 × CH
3
CO), 13.7 (SCH
Na (M + Na) 1271.2621. Found
3
);
2 4
H O, dried (MgSO ) and the solvent evaporated. The residue was
+
+
HRMS (ESI ) calcd for C49
H
68
O
29
S
4
2
purified by flash chromatography (90% Et O/acetone) to give 11
1
271.2639.
(5.6 mg, 30%).
4
.15.2. Methyl S-(2,3,4-tri-O-acetyl-6-deoxy-6-iodo-α-
D
-
D
4.17. Methyl S-(α-
mannopyranosyl)-(1→6)-S-(6-thio-α-
(6-thio-α- -mannopyranosyl)-(1→6)-S-(6-thio-α-
mannopyranosyl)-(1→6)-(1,6-dithio-α- -mannopyranoside) (3)
D
-mannopyranosyl)-(1→6)-S-(6-thio-α-
D
-
mannopyranosyl)-(1→6)-S-(2,3,4-tri-O-acetyl-6-thio-α-
mannopyranosyl)-(1→6)-S-(2,3,4-tri-O-acetyl-6-thio-α-
mannopyranosyl)-(1→6)-(2,3,4-tri-O-acetyl-1,6-dithio-α-
-
-
D
-mannopyranosyl)-(1→6)-S-
D
D
D
-
D
-
D
mannopyranoside) (10)
A solution of triphenylphosphine (16.1 mg, 0.0614 mmol), im-
idazole (7.3 mg, 0.11 mmol), iodine (11.0 mg, 0.043 mmol) and alcohol
A solution of thiomannoside 11 (50.0 mg, 0.0387 mmol) was
treated with 1 M aq NaOMe in methanol (50 μL) at rt with stirring
for 4 h. The solution was adjusted to pH 5–6 with Amberlite IR-
(51.4 mg 37.8 μmol) in toluene (4 ml) was heated at 70 °C with stir-
+
ring for 1 h. The solvent was evaporated to dryness under reduced
120 resin (H form), filtered, and the filtrate evaporated to dryness
Please cite this article in press as: Tyson Belz, Spencer J. Williams, A building block approach to the synthesis of a family of S-linked α-1,6-oligomannosides, Carbohydrate Research
2016), doi: 10.1016/j.carres.2016.04.015
(