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Page 1: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

Supporting Information

© Wiley-VCH 2007

69451 Weinheim, Germany

Page 2: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04
SEberle
Synthesis of Pentaantennary N-Glycans Carrying Bisecting GlcNAc and Core-Fucose** Steffen Eller, Ralf Schuberth, Gislinde Gundel, Joachim Seifert and Carlo Unverzagt*
Page 3: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

LC-MS analysis of products obtained by glycosylation of 17 with a 9:1 mixture of 8 and 9

C196H200F3N11O85 M calc: 4124.16; 4126.17 (100%)

M found: 4147.11 [M+Na]+

05.0 10.0 15.0 20.0 t [min]

rel. Int. [%]100

4060 4080 4100 4120 4140 4160 4180 4200m/z [amu]

0

0

4119.37

4116.784076.68

4142.244123.25 4147.11

4077.43

4074.864104.614100.20

4081.734119.37

rel. Int. [%]

rel. Int. [%]

4163.29

2322

22

23

RP-HPLC ESI-MS

C194H198F3N11O84 M calc: 4082.15; 4084.16 (100%)

M found: 4105.03 [M+Na]+

Page 4: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

3600 3650 3700 3750 3800 3850 3900 3950 4000 4050 4100 4150 4200 4250 4300 4350 4400 44500

100 4147.73

4147.08

4121.004119.92

4118.84

4105.89

4105.13

4078.98

4069.31

4148.81

4149.03

4149.79

4164.87

4165.63

4166.06

4166.93

4167.37

4167.80

4169.11

4171.50

4172.91

4186.51

4144 4146 4148 4150 4152 4154 4156 4158 4160 4162 4164 4166 4168 4170 4172 41740

100

%

4147.73

4147.08

4145.78

4144.80

4148.81

4149.03

4149.79

4164.87

4163.67

4162.81

4150.87

4151.20

4151.524161.834151.74

4152.06

4152.61

4153.04

4153.80

4161.07

4165.63

4166.06

4166.93

4167.37

4167.80

4169.114170.84

4171.50

4172.914173.24

m/z [amu]

rel. Int. [%]C196H200F3N11O85M calc: 4124.16; 4126.17 (100%)

M found: 4147.08 [M+Na]+

22

Page 5: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

3750 3800 3850 3900 3950 4000 4050 4100 4150 4200 4250 43000

100 4076.32

4075.89

4074.82

4073.64

4016.724016.084014.80

4017.144018.744019.59

4033.52

4077.17

4078.35

4078.57

4079.42

4079.74

4080.284103.754105.25

4106.43

4138.484136.97 4139.77

rel. Int. [%]

m/z [amu]

23 C194H198F3N11O84 M calc: 4082.15; 4084.16 (100%)

M found: 4105.25 [M+Na]+

4077.17 [M-N +Na]+2

4072 4074 4076 4078 4080 4082 4084 4086 4088 4090 4092 4094 4096 4098 4100 4102 4104 4106 4108 4110 4112 41140

100 4076.32

4075.89

4074.82

4073.64

4077.17

4078.35

4078.57

4079.42

4079.74

4080.284103.75

4103.10

4092.274080.924091.52

4090.34

4093.774102.25

4095.17 4101.174099.03

4104.294105.25

4106.43

4107.18

4108.58

Page 6: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

3450 3500 3550 3600 3650 3700 3750 3800 3850 3900 3950 4000 4050 4100 4150 4200 4250 4300 4350 4400 44500

100

%

3977.24

3977.03

3976.71

3976.39

3975.97

3975.75

3975.44

3974.90

3974.48

3593.36

3592.55

3592.15

3535.19

3533.09 3591.14

3594.87

3917.913595.28

3917.49

3914.54

3978.94

4005.05

4006.43

4007.29

4007.61

4008.68

4041.84

4060.41

4099.41

m/z [amu]

rel. Int. [%]

OAcO

OO

NPht

O

AcO

AcOAcO

O

NPht

AcO

AcOAcO

O

AcO

OOAc

O

NPht

BzlO N3O

NPht

OBzl

OBzlO O

O

NHTFAc

AcO

AcOAcO

OHO

O

O

O

NHTFAc

O

AcO

AcOAcO

O

NHTFAc

AcO

AcOAcO

O

O

NHTFAc

AcO

AcOAcO

O

O OMe

24

3974 3976 3978 3980 3982 3984 3986 3988 3990 3992 3994 3996 3998 4000 4002 4004 4006 4008 4010 40120

100 3976.92

3976.60

3975.54

3974.90

3977.35

3977.99

3978.63

3978.94

4000.033979.58

3998.97

3980.11

3980.54

3980.97

3998.013981.50

3997.58

4003.774001.53

4002.59

4005.69

4005.90

4006.43

4006.76

4007.29

4008.574011.77

Page 7: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

3950 4000 4050 4100 4150 4200 4250 4300 4350 4400 4450 4500 4550 4600 4650 4700 4750 4800 4850 4900 49500

100

%

4377.734377.39

4376.50

4375.83

4375.50

4374.71

4374.49

4316.804257.414287.93

4378.51

4378.84

4379.29

4380.29

4380.63

4381.08

4403.544405.44

4407.23

4408.354409.70

rel. Int. [%]

m/z [amu]

O

AcO

OO

NPht

O

AcO

AcOAcO

O

NPht

AcO

AcOAcO

O

AcO

O

OAc

O

NPht

BzlO N3O

NPht

OBzl

OBzlO O

O

NHTFAc

AcO

AcOAcO

O

HO

O

O

O

NHTFAc

O

AcO

AcOAcO

O

NHTFAc

AcO

AcOAcO

O

O

NHTFAc

AcO

AcOAcO

O

OH3COMpm

OMpmMpmO

O

4370 4372 4374 4376 4378 4380 4382 4384 4386 4388 4390 4392 4394 4396 4398 4400 4402 4404 4406 4408 4410 4412 44140

1004377.77

4376.83

4375.94

4375.50

4374.71

4374.49

4374.16

4378.06

4378.51

4379.51

4380.52

4381.30

4405.554404.214394.93

4393.254382.64

4392.134390.794383.31

4383.754389.90

4403.654400.294399.06

4398.06

4406.56 4408.02

4411.824409.81

26

Page 8: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

O

AcO

OO

NPht

O

AcO

AcOAcO

O

NPht

AcO

AcOAcO

O

AcO

O

OAc

O

NPht

BzlO N3O

NPht

OBzl

OBzlO O

O

NPht

AcO

AcOAcO

O

HO

O

O

O

NPht

O

AcO

AcOAcO

O

NPht

AcO

AcOAcO

O

O

NHTFAc

AcO

AcOAcO

O

O OMe

23

HCO2H

Page 9: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

O

AcO

OO

NPht

O

AcO

AcOAcO

O

NPht

AcO

AcOAcO

O

AcO

O

OAc

O

NPht

BzlO N3O

NPht

OBzl

OBzlO O

O

NHTFAc

AcO

AcOAcO

O

HO

O

O

O

NHTFAc

O

AcO

AcOAcO

O

NHTFAc

AcO

AcOAcO

O

O

NHTFAc

AcO

AcOAcO

O

O OMe

24

Page 10: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

O

AcO

OO

NPht

O

AcO

AcOAcO

O

NPht

AcO

AcOAcO

O

AcO

O

OAc

O

NPht

BzlO N3O

NPht

OBzl

OBzlO O

O

NHTFAc

AcO

AcOAcO

O

HO

O

O

O

NHTFAc

O

AcO

AcOAcO

O

NHTFAc

AcO

AcOAcO

O

O

NHTFAc

AcO

AcOAcO

O

OH3COMpm

OMpmMpmO

O

26

HCO2H

Page 11: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

Compound 24: 14.3 mg (3.59 µmol, 46.6 % yield),

Rf = 0.21 (hexane/acetone, 1:1), [α]D26 = -4.7 (0.9, CH2Cl2),

C176H189F12N11O81 (3982.4),

ESI-MS (100 % acetonitrile): Mcalcd. = 3980.1 Mfound = 4003.8 (M+Na)+,

1H-NMR (500 MHz, [D6]DMSO, 298 K): δ = 9.62 (br, 3H, NH), 9.06 (br, 1H, NH),

7.91-7.64 (m, 16H, NPht), 7.46-6.01 (m, 19H, Ar), 5.64-5.52 (m, 2H, H-35’, H-35),

5.42-5.16 (m, 8H, H-15, H-3B, H-15’, H-12, H-11, H-36’, H-36’’, H-36), 5.12-5.00 (m, 5H, H-45,

H-46, H-4B, H-34, H-16), 4.97 (dd, J3,4 = 9.4 Hz, J4,5 = 8.8 Hz, 1H, H-45’), 4.91-4.76 (m, 5H,

H-46’, H-46’’, H-16’, CH2O, H-23), 4.70 (d, J1,2 = 7.4 Hz, 1H, H-16’’), 4.64-4.49 (m, 5H, H-13,

CH2O, H-14, H-14’, CH2O), 4.44 (d, Jgem = 12.8 Hz, 1H, CH2O), 4.39-4.16 (m, 10H, H-1B,

H-2B, H-6a5’, H-6a5, CH2O, CH2O, H-31, H-6a6’’, H-6a6’, H-6a6), 4.15-3.89 (m, 18H, H-6b5,

H-6aB, H-6b6’, H-6b6’’, H-6a4, H-55’, H-25, H-55, H-6b5’, H-24, H-25’, H-22, H-41, H-32, H-42,

H-6b4, H-33, H-24’), 3.88-3.61 (m, 22H, H-6b6, H-6a1, H-21, H-6a2, H-56’’, H-51, H-5B, H-53,

H-6b1, H-6bB, H-26’, H-56’, H-26’’, H-56, H-43, H-6a4’, H-34’, PhOCH3, H-51, H-54’),

3.55-3.37 (m, 8H, H-26, H-6a3, H-41, H-44’, H-6b2, H-6b4’, H-52, H-6b3), 2.12-1.62 (m, 63H,

21 OAc),

13C-NMR (125 MHz, [D6]DMSO, 298 K): δ = 170.1, 170.1, 170.0, 170.0, 169.9, 169.8,

169.7, 169.6, 169.3 (C=O, OAc), 168.0, 167.4, 167.1 (C=O, NPht), 156.9, 156.6, 156.4,

156.3 (C=O, TFA), 153.4, 151.9 (C-4, C-1; OMp), 138.1, 137.8 (C-1, Ar), 135.0,

134.9 (C-4/5, NPht), 130.6, 130.5, 130.4 (C-1/2, NPht), 128.2, 128.0, 127.8, 127.7, 127.5,

127.3, 126.9, 126.7 (C, Ar), 123.7, 123.5, 123.2 (C-3/6, NPht), 116.9, 116.8, 115.9 (CF3),

115.8 (q, 1JC,F = 287.5 Hz, CF3), 115.3, 114.4 (C-2, C-3, C-5, C-6; OMp), 101.4 (C-1B),

99.7 (C-16’’), 99.5 (C-13), 99.3 (C-16), 98.5 (C-16’), 97.1 (C-14), 97.1 (C-12), 96.1 (C-14’),

95.7 (C-15), 95.3 (C-15’), 84.4 (C-11), 77.6 (C-24), 77.1 (C-31), 76.7 (C-52), 76.2 (C-32),

76.2 (C-42), 76.1 (C-44), 75.9 (C-31), 74.7 (C-51), 74.4 (C-54’), 73.6 (C-24’), 73.6 (CH2O),

73.0 (CH2O), 72.5 (C-44’), 72.2 (C-36’), 72.2 (CH2O), 71.6 (C-3B), 71.6 (C-36’’), 71.6 (C-5B),

71.1 (C-36), 71.1 (C-56’), 71.1 (C-56), 70.7 (C-34’), 70.6 (C-56’’), 70.6 (C-41), 70.6 (C-55),

70.3 (C-55’), 70.1 (C-31), 69.9 (C-35), 69.9 (C-35’), 69.2 (C-4B), 68.8 (C-34), 68.3 (C-45’),

68.3 (C-64’), 68.3 (C-54), 68.1 (C-46), 68.1 (C-46’), 68.1 (C-23), 67.7 (C-46’’), 67.3 (C-45),

66.9 (C-63), 66.4 (C-61), 62.9 (C-6B), 61.9 (C-62), 61.5 (C-65), 61.5 (C-66), 61.5 (C-66’’),

61.5 (C-66’), 61.2 (C-64), 60.7 (C-65’), 56.1 (C-22), 55.1 (PhOCH3), 54.8 (C-26), 54.3 (C-25’),

Page 12: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

54.2 (C-41), 54.2 (C-26’), 54.1 (C-25), 54.1 (C-26’’), 53.9 (C-2B), 20.6, 20.5, 20.4, 20.4, 20.3,

20.2, 20.1, 20.0 (CH3, OAc).

Compound 26: 8.4 mg (1.92 µmol, 75 % yield),

Rf = 0.20 (hexane/acetone, 1:1),

[α]D26 = -26.1 (1.1, CH2Cl2),

C176H189F12N11O81 (4382.9),

ESI-MS (100 % acetonitrile): Mcalcd. = 4380.3 Mfound = 4403.5 (M+Na)+,

1H-NMR (500 MHz, [D6]DMSO, 298 K): δ = 9.67-9.35 (m, 3H, NH), 8.62 (br, 1H, NH),

7.91-7.59 (m, 16H, NPht), 7.34-6.66 (m, 27H, Ar), 5.65-5.51 (m, 2H, H-35’, H-35),

5.42-5.32 (m, 3H, H-15, H-3B, H-15’), 5.29-5.20 (m, 3H, H-12, H-36’, H-36’’), 5.18 (d,

J1,2 = 9.5 Hz, 1H, H-11), 5.12-4.92 (m, 7H, H-36, H-45, H-4B, H-46’, H-34, H-16, H-45’),

4.88-4.73 (m, 6H, H-46’’, H-46, CH2O, H-16’, H-1F, H-23), 4.71-4.27 (m, 19H, CH2O, H-16’’,

CH2O, CH2O, H-13, H-14, H-14’, CH2O, CH2O, CH2O, H-1B, CH2O, CH2O, CH2O, CH2O,

H-2B, CH2O, H-6a5’, H-6a5), 4.22-3.87 (m, 22H, H-6a6’’, H-32, H-6a6’, H-31, H-6aB, H-6a4,

H-6b5, H-25, H-55’, H-55, H-6b5’, H-6b6’’, H-24, H-42, H-25’, H-22, H-6b6’, H-24’, H-41, H-33,

H-6a6, H-6b4), 3.87-3.59 (m, 26H, H-21, H-6a1, H-56’, H-56’’, H-43, H-26’, H-6b6, H-6bB, H-5B,

H-53, PhOCH3, H-56, H-26’’, H-34’, H-5F, H-6a4’, H-2F, H-3F), 3.58-3.17 (m, 14H, H-4F, H-26,

H-51, H-6a3, H-54, H-44’, H-54’, H-6b1, H-6a2, H-6b4’, H-52, H-44, H-6b3, H-6b2),

2.06-1.65 (m, 63H, 21 OAc), 0.90 (d, J5,6 = 5.9 Hz, 3H, H-6F),

13C-NMR (125 MHz, [D6]DMSO, 298 K): δ = 170.8, 170.7, 170.6, 170.4, 170.0, 169.7 (C=O,

OAc), 167.1, 166.9, 166.7 (C=O, NPht), 159.4, 159.3 (C-4, Mpm), 156.5, 156.3, 156.2 (C=O,

TFA), 139.0, 138.5 (C-1, Ar), 135.7, 135.6 (C-4/5, NPht), 132.6, 132.0, 131.7, 131.5,

131.4 (C-1, Mpm; C-1/2, NPht), 130.3, 129.6, 128.9, 128.6, 128.5, 128.4, 128.2, 127.9,

127.6 (C-2/6, Mpm; C, Ar), 124.9, 124.4, 124.2, 123.3 (C-3/6, NPht), 116.8, 115.0,

114.6 (CF3), 114.4 (C-3/5, Mpm), 101.0 (C-1Bβ , 1JC-1,H-1 = 163.2 Hz), 99.5 (C-16’’β,1JC-1,H-1 = 163.8 Hz), 99.5 (C-13β , 1JC-1,H-1 = 166.8 Hz), 98.5 (C-16β , 1JC-1,H-1 = 165.0 Hz),

98.5 (C-16’β , 1JC-1,H-1 = 166.8 Hz), 97.1 (C-14α , 1JC-1,H-1 = 178.6 Hz), 96.9 (C-12β,1JC-1,H-1 = 167.2 Hz), 96.5 (C-14’α , 1JC-1,H-1 = 177.4 Hz), 95.6 (C-15β , 1JC-1,H-1 = 166.5 Hz),

95.4 (C-15’β , 1JC-1,H-1 = 167.2 Hz), 93.9 (C-1Fα , 1JC-1,H-1 = 174.0 Hz), 84.2 (C-11β,1JC-1,H-1 = 167.5 Hz), 77.6 (C-3F), 76.9 (C-4F), 76.7 (C-24), 76.7 (C-52), 76.2 (C-43),

75.9 (C-32), 75.9 (C-31), 75.7 (C-42), 75.6 (C-41), 75.6 (C-51), 73.9 (C-2F), 73.6 (CH2O),

Page 13: 69451 Weinheim, Germany - Wiley-VCH · 2007. 5. 16. · 4145.78 414 4.80 4148.81 4149.03 4149.79 4164.87 4163.67 4162.81 4150 .87 4151.20 4151.52 4161.83 4151.74 4152.06 4152.61 4153.04

73.6 (C-24’), 73.6 (C-44’), 73.0 (CH2O), 72.6 (C-54’), 71.8 (CH2O), 71.8 (C-36’), 71.4 (C-3B),

71.4 (C-56’’), 71.2 (C-36’’), 71.2 (C-36), 70.9 (CH2O), 70.6 (C-56), 70.6 (CH2O), 70.5 (C-55),

70.5 (C-56’), 70.5 (C-5B), 70.5 (C-53), 70.5 (CH2O), 70.5 (C-44), 70.0 (C-55’), 69.8 (C-35),

69.7 (C-34), 69.5 (C-35’), 69.5 (C-54), 69.1 (C-4B), 68.1 (C-34’), 68.1 (C-64’), 68.1 (C-33),

68.9 (C-46’), 68.9 (C-45’), 68.9 (C-46’’), 68.9 (C-46), 68.9 (C-23), 67.3 (C-45), 66.9 (C-63),

65.4 (C-5F), 63.9 (C-62), 62.6 (C-6B), 61.7 (C-61), 61.2 (C-65), 61.2 (C-66’’), 61.2 (C-66’),

61.2 (C-64), 61.2 (C-66), 60.6 (C-65’), 55.6 (C-22), 54.5 (C-26’), 54.6 (C-26), 54.6 (PhOCH3),

54.3 (C-25’), 54.2 (C-21), 54.0 (C-25), 53.8 (C-2B), 53.8 (C-26’’), 21.3, 21.2, 20.9, 20.8 (CH3,

OAc), 16.9 (C-6F).

CH-coupling constants determined by coupled HSQC experiment:

G. Bodenhausen, D. J. Ruben, Chem. Phys. Lett. 1980, 69, 185-188.