10.1002/ejoc.202000923
European Journal of Organic Chemistry
FULL PAPER
To a solution of donor 5b1 (1.09 g, 0.20 mmol), activated 4 Å molecular
sieves (700 mg) in dry dichloromethane (10 mL), were added a solution
of acceptor 7a6 (1.0 g, 1.82 mmol) and N-iodosuccinimide (470 mg, 2.09
mmol) in dry dichloromethane (15 mL) stirred for 1 hour at room
temperature. TfOH (0.47 mL, 0.55 mmol) was added slowly dropwise
over 5 minutes to the reaction mixture and stirred for 16 hours at 0 oC.
The reaction was quenched by trimethylamine, filtered through celite pad
and extracted with dichloromethane (30 mL x 3) and saturated sodium
thiosulfate solution. The organic layer was treated with MgSO4, filtered,
and the solvent evaporated under reduced pressure. The residue was
purified by flash column chroma-tography on silica gel to afford product
18 (1.22 g, 70%) as a white solid. Rf 0.59 (EtOAc/Hexane = 1/4); mp 92-
94 oC; [α]25D -92.47 (c 1.0 , CH2Cl2); IR (NaCl) v 3414, 2106, 1748, 1718,
1645 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.86-7.76 (m, 3H, Ar-H), 7.75-
7.72 (m, 3H, Ar-H), 7.60-7.58 (m, 2H, Ar-H), 7.51-7.45 (m, 5H, Ar-H),
7.39-7.38 (m, 3H, Ar-H), 7.28-7.20 (m, 3H, Ar-H), 7.03 (d, J = 6.0 Hz, 2H,
Ar-H), 5.87 (t, J = 10.0 Hz, 1H), 5.57 (s, 1H, PhCH), 5.53 (d, J = 8.4, 1H),
5.00 (d, J = 11.2 Hz, 1H), 4.86 (d, J = 11.2 Hz, 1H), 4.60 (d, J = 10.8 Hz,
1H), 4.48 (d, J = 7.2 Hz, 1H), 4.41-4.36 (m, 2H), 4.32 (d, J = 10.8 Hz, 1H),
4.05 (d, J = 10.0 Hz, 1H), 3.88-3.79 (m, 2H), 3.77-3.69 (m, 2H), 3.46-3.42
(m, 1H), 3.39-3.36 (m, 2H), 3.34-3.25 (m, 2H), 1.90 (s, 3H), 0.89 (s, 9H),
0.08 (s, 3H), 0.00 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.0, 137.4,
136.8, 135.3, 134.0, 133.1, 132.8, 131.1, 130.7, 129.9, 129.01, 128.2,
128.1, 128.0, 127.8, 127.6, 127.5, 127.5, 126.5, 126.1, 125.9, 125.9,
125.8, 123.3, 101.5, 98.0, 96.9, 82.4, 79.0, 77.5, 75.2, 74.7, 74.1, 69.8,
68.5, 68.3, 67.9, 66.1, 55.0, 30.7, 25.4, 20.4, 17.7, -4.4, -5.6; HRMS (ESI,
M+Na+) calcd for C53H58N4O12SiNa 993.3718, found 993.3707.
pyranosyl-(1→6)-3-O-(2-naphtha-lenylmethyl)-4-O-benzyl-2-deoxy-2-
azido-β-D-glucopyranoside (22)
To a solution of 19 (650 g, 0.55 mmol) in dry dichloromethane (6.0 mL),
lauric acid 17 (440 mg, 2.19 mmol), N-(3-dimethylaminopropyl)-N-
ethylcarbodiimide (240 μL, 1.40 mmol) and 4-dimethylaminopyridine (66
mg, 0.60 mmol) were added at 0 oC under nitrogen atmosphere. After 10
minutes the reaction slowly warmed up to room temperature. After
stirring for 16 hours, the mixture was extracted with water and
dichloromethane (40 mL x 4). The organic layer was treated with MgSO4,
filtered, and the solvent evaporated under reduced pressure. The residue
was purified by flash column chromatography on silica gel to afford
product 22 (701 mg, 92%) as a white solid. Rf 0.38 (EtOAc /Hexane =
1/4); mp 96-98 oC; [α]25D -107.20 (c 1.0, CH2Cl2); IR (NaCl) v 3308, 2925,
2854, 2112, 1736, 1664, 1541, 1464, 1374, 1254, 1100, 1072 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.83-7.80 (m, 2H, Ar-H), 7.79-7.76 (m, 2H, Ar-
H), 7.48-7.44 (m, 3H, Ar-H), 7.43-7.39 (m, 2H, Ar-H), 7.35-7.32 (m, 3H,
Ar-H), 7.30-7.28 (m, 2H, Ar-H), 7.25-7.23 (m, 2H, Ar-H), 6.02 (d, J = 9.2
Hz, 1H), 5.96 (d, J = 9.2 Hz, 1H), 5.48 (s, 1H, PhCH), 5.27 (q, J = 9.6 Hz ,
1H), 5.03 (d, J = 11.2 Hz, 1H), 5.00-4.97 (m, 1H), 4.91 (d, J = 11.2 Hz,
1H), 4.82 (d, J = 11.2 Hz, 1H), 4.61 (d, J = 10.8 Hz, 1H), 4.53-4.50 (m,
1H), 4.30-4.23 (m, 1H), 4.05 (q, J =10 Hz, 1H), 3.98-3.93 (m, 2H), 3.81-
3.68 (m, 3H), 3.66-3.63 (m, 1H), 3.55-3.47 (m, 2H), 3.44-3.40 (m, 2H),
3.36-3.31 (m, 1H), 2.40-2.19 (m, 6H), 1.58-1.50 (m, 6H), 1.24 (s, 50H),
0.95 (s, 9H), 0.87 (t, J = 6.4 Hz, 9H), 0.17 (s, 6H); 13C NMR (100 MHz,
CDCl3) δ 173.8, 173.1, 169.2, 138.0, 136.9, 135.4, 133.1, 132.9, 128.8,
128.3, 128.02, 127.97, 127.8, 127.61, 127.56, 127.51, 126.6, 126.5,
125.9 125.7, 100.9, 97.0, 82.6, 78.8, 77.4, 75.2, 74.6, 74.4, 71.8, 71.7,
70.7, 70.5, 68.5, 66.9, 66.4, 65.8, 53.7, 53.4, 41.4, 34.4, 34.3, 34.1, 34.0,
31.8, 29.6, 29.4, 29.3, 29.3, 29.12, 29.09, 28.96, 25.5, 25.2, 25.1, 25.0,
24.9, 22.6, 17.8, 14.0, -4.1, -5.4; HRMS (ESI, M+Na+) calcd for
C81H124N4O13SiNa 1411.8831, found 1411.8835.
1-O-tert-butyldimethylsiyl-4,6-O-benzylidene-2-deoxy-2-[(R)-3-
(dodecanoyloxy)-tetradecanamido]-β-D-gluco-pyranosyl-(1→6)-3-O-
(2-naphthalenylmethyl)-4-O-benzyl-2-deoxy-2-azido-β-D-gluco-
pyranoside (21)
To a solution of disaccharide 18 (620 mg, 0.64 mmol) in ethanol (10.0
mL), hydrazine (5.0 mL) was added at room temperature under nitrogen
atmosphere, the reaction was allowed to stir at 80 oC overnight. After
completion of the reaction, it was extracted with ethyl acetate (30 mL x 3)
and water. The organic layer was treated with MgSO4, filtered and
evaporated under reduced pressure. The residue was dried over high
vacuum for one day and used in next step without further purification. To
the amine intermediate (390 mg, 0.48 mmol) in dry dichloromethane
were added myristic acid derivative 20 (860 g, 1.94 mmol) and dropwise
addition of N-(3-Dimethyl-aminopropyl)-N-ethylcarbodiimide (282 μL,
1.60 mmol) at 0 oC under nitrogen atmosphere. After 20 minutes the
reaction was warmed up to room temperature. After stirring for 16 hours,
the mixture was diluted with dichloromethane (20 x 3) and extracted with
water. The organic layer was treated with MgSO4, filtered, and the
solvent evaporated under reduced pressure. The residue was purified by
flash column chromatography on silica gel to afford product 21 (415 mg,
1-O-tert-butyldimethylsiyl-4,6-O-benzylidene-2-deoxy-2-[(R)-3-
(dodecanoyloxy)-tetradecanamido]-3-O-dodec-anoyl-β-D-gluco-
pyranosyl-(1→6)-4-O-benzyl-2-deoxy-2-azido-β-D-glucopyranoside
(23)
To a solution of 22 (340 mg, 0.24 mmol) in a mixture of CH2Cl2/H2O (9:1)
(5.0 mL) solvent, 2,3-dichloro-5,6-dicyano-1,4-benzo-quinone (76 mg,
0.34 mmol) was added at room temperature under nitrogen atmosphere
and stirred for 4 hours, the mixture was diluted by dichloromethane and
extracted with aqueous 10% sodium hydroxide solution, then the organic
layer was washed with brine solution and treated with MgSO4, filtered,
and the solvent evaporated under reduced pressure. The residue was
purified by flash column chromatography on silica gel to afford product 23
(284 mg, 94%) as a white solid. Rf 0.27 (EtOAc /Hexane = 1.5/3.5); mp =
108-110 oC; [α]25D-32.70 (c 1.0, CH2Cl2); IR (NaCl) v 3308, 3365, 2925,
2855, 2114, 1737, 1665, 1542, 1464, 1375, 1257, 1181, 1014 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.43-7.74 (m, 2H, Ar-H), 7.37-7.27 (m, 8H, Ar-
H), 6.11 (d, J = 9.2 Hz, 1H), 5.98 (d, J = 9.2 Hz, 1H), 5.48 (s, 1H, PhCH),
5.31-5.23 (m, 1H), 5.04-4.97 (m, 1H), 4.81 (d, J = 4.4 Hz, 1H), 4.79 (d, J
= 4.8 Hz, 1H), 4.65 (dd, J =11.2, 7.6 Hz, 1H), 4.58 (t, J = 8.0 Hz, 1H),
4.52-4.49 (m, 1H), 4.30-4.25 (m, 1H), 4.06-4.02 (m, 2H), 3.96-3.92 (m,
1H), 3.76-3.71 (m, 2H), 3.66 (t, J = 10.0 Hz, 1H), 3.53-3.48 (m, 1H), 3.45-
3.43 (m, 2H), 3.39-3.37 (m, 1H), 3.23-3.18 (m, 1H), 2.73 (d, J = 12.0 Hz,
1H), 2.42-2.24 (m, 6H), 1.58-1.51 (m, 6H), 1.25 (s, 50H), 0.94 (s, 9H),
0.88 (t, J = 6.8 Hz, 9H), 0.16 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 173.9,
173.74, ,173.68 169.44, 169.39 138.2, 136.9, 129.0, 128.5, 128.1, 128.0,
127.9, 127.8, 126.0, 101.2, 97.0, 78.7, 77.5, 75.0, 74.5, 74.3, 71.6, 71.4,
71.0, 68.5, 67.5, 67.2, 66.3, 54.3, 54.2, 41.6, 34.5, 34.2, 34.1, 31.9,
29.61, 29.59, 29.5, 29.44, 29.39, 29.32, 29.17, 29.0, 25.6, 25.3, 25.2,
24.99, 24.96 22.6, 17.9, 14.1, -4.0 -5.27, -5.30; HRMS (ESI, M+Na+)
calcd for C70H117N4O13Si 1249.8386, found 1249.8380.
71%) as colourless viscous liquid. Rf 0.57 (EtOAc/Hexane = 1/3); [α]25
-
D
80.50 (c 1.0, CH2Cl2); IR (NaCl) v 3289, 2926, 2855, 2109, 1731, 1714,
1650, 1554, 1465, 1378, 1258, 1174, 1072 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.73-7.76 (m, 4H, Ar-H), 7.750-7.44 (m, 5H, Ar-H), 7.37-7.29 (m,
6H, Ar-H), 7.25-7.23 (m, 2H, Ar-H), 6.26 (d, J = 6.0 Hz, 1H), 6.16 (d, J =
6.4 Hz, 1H), 5.53 (s, 1H, PhCH), 5.12-5.07 (m, 1H), 5.04 (d, J = 11.2 Hz,
1H), 4.92 (d, J = 11.2 Hz, 1H), 4.86-4.82 (m, 2H), 4.60 (d, J = 10.8 Hz,
1H), 4.53 (t, J = 5.6 Hz, 1H), 4.30-4.25 (m, 1H), 4.18 (t, J = 11.2 Hz, 1H),
4.02 (t, J = 7.2 Hz, 1H), 3.74 (t, J = 11.2 Hz, 1H), 3.73 (t, J = 10.8 Hz, 1H),
3.55-3.42 (m, 5H), 5.40-3.32 (m, 2H), 2.33-2.25 (m, 4H), 1.64-1.55 (m,
4H), 1.23 (2, 34H), 0.95 (s, 9H), 0.87 (t, J = 5.6 Hz, 6H), 0.17 (s, 6H); 13
C
NMR (100 MHz, CDCl3) δ 174.3, 171.2, 137.8, 137.1, 135.4, 133.2,
133.0, 129.1, 128.5, 128.19, 128.15, 127.9, 127.73, 127.70, 127.6, 126.7,
126.3, 126.1, 126.0, 125.9, 101.8, 99.8, 97.0, 82.7, 81.3, 78.0, 75.5, 74.9,
74.4, 71.4, 70.4, 68.7, 68.6, 67.6, 66.3, 59.1, 42.5, 34.5, 34.4, 33.9, 31.9,
29.6, 29.51, 29.48, 29.4, 29.31, 29.28, 29.13, 29.07, 25.6, 22.7, 17.9,
14.1, -4.1, -5.3; HRMS (ESI, M+) calcd for C69H102N4O12Si 1206.7264,
found 1207.7350.
1-O-tert-butyldimethylsiyl-4,6-O-benzylidene-2-deoxy-2-[(R)-3-
(dodecanoyloxy)-tetradecanamido]-3-O-dodec-anoyl-β-D-gluco-
pyranosyl-(1→6)-3-O-dodecanoyl-4-O-benzyl-2-deoxy-2-azido-β-D-
glucopyranoside (24)
1-O-tert-butyldimethylsiyl-4,6-O-benzylidene-2-deoxy-2-[(R)-3-
(dodecanoyloxy)-tetradecanamido]-3-O-dodec-anoyl-β-D-gluco-
To a solution of 23 (360 mg, 0.28 mmol) in dichloromethane (4.0 mL),
lauric acid 17 (0.28 g, 1.14 mmol), N-(3-dimethyl-aminopropyl)-N-
14
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