Post on 25-Oct-2020
S1
Supporting Information
for
The Amadori rearrangement as glycoconjugation
method: Synthesis of non-natural C-glycosyl type
glycoconjugates
Katharina Gallas¶, Gerit Pototschnig¶, Florian Adanitsch, Arnold E. Stütz and Tanja M.
Wrodnigg*
Address: Glycogroup, Institute of Organic Chemistry, Technical University Graz,
Stremayrgasse 9, A-8010 Graz, Austria
Email: Tanja M. Wrodnigg – t.wrodnigg@tugraz.at
¶ These authors contributed equally to this work.
* Corresponding author
NMR data of compounds 16, 19, 23–36.
General
NMR spectra were recorded on a Bruker Ultrashield spectrometer at 300.36 and 75.53 MHz,
respectively in methanol-d4 or D2O as indicated. Chemical shifts are listed in delta employing
residual, non-deuterated solvent as the internal standard. Structures of crucial intermediates
were unambiguously assigned by 1D-TOCSY and HSQC experiments.
S2
D-glycero-L-manno/L-gluco-heptopyranose 16a and 16b 1H, 300 MHz, D2O
O
HOOH
HOOH
OH
OH
16
S3
D-glycero-L-manno/L-gluco-heptopyranose 16a and 16b 13C, 75 MHz, D2O
O
HOOH
HOOH
OH
OH
16
S4
1-(N,N-Dibenzylamino)-1-deoxy-αααα-D-galacto-hept-2-ulopyranose (23a) and -furanose (23b), 1H, 300 MHz, MeOH-d4
O
HO OHOH
HO
+O
OH
OHHO
HOOH
NBn2OHNBn2
23a 23b
S5
1-(N,N-Dibenzylamino)-1-deoxy-αααα-D-galacto-hept-2-ulopyranose (23a) and -furanose (23b), 13C, 75 MHz, MeOH-d4
O
HO OH
OH
HO
+O
OH
OHHO
HOOH
NBn2OHNBn2
23a 23b
S6
1-(N-(6-Hydroxyhexyl)amino)-1-deoxy-αααα-d-galacto-hept-2-ulopyranose (24a) and –furanose (24b) 1H, 300 MHz, MeOH-d4
O
HO OHOH
HO
+O
OH
OHHO
HO
OH
NH(CH2)6OHOHNH(CH2)6OH
24a 24b
S7
1-(N-(6-Hydroxyhexyl)amino)-1-deoxy-αααα-d-galacto-hept-2-ulopyranose (24a) and –furanose (24b) 13C, 75 MHz, MeOH-d4
O
HO OHOH
HO
+O
OH
OHHO
HO
OH
NH(CH2)6OHOHNH(CH2)6OH
24a 24b
S8
1-(N-(6-Hydroxyhexyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-galacto-hept-2-ulopyranose 26a and -furanose 26b 1H, 300 MHz, MeOH-d4
1253.683
1216.865
1211.323
1173.085
1166.772
1160.464
1156.732
1150.222
1148.015
1145.341
1137.655
1135.411
1127.880
1122.121
1116.191
1114.331
1109.952
1104.806
1099.978
1094.289
1086.690
1083.704
1080.800
1074.332
1067.764
1046.875
1036.979
1014.198
1005.710
1004.119
1002.581
1000.940
999.332
995.870
992.277
985.571
912.571
868.756
489.815
482.914
476.681
471.116
464.503
458.044
440.125
419.071
415.952
O
HO OHOH
HOO
N(CH2)6OH
O O
OHHO
HO
OH
O
N(CH2)6OH
O+
26a 26b
S9
1-(N-(6-Hydroxyhexyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-galacto-hept-2-ulopyranose 26a and -furanose 26b 13C, 75 MHz, MeOH-d4
O
HO OHOH
HOO
N(CH2)6OH
O O
OHHO
HO
OH
O
N(CH2)6OH
O+
26a 26b
S10
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-deoxy-αααα-D-galacto-hept-2-ulopyranose (25a) and –furanose (25b) 1H, 300 MHz, MeOH-d4
PPM 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2 1.0
1175.366
1170.547
1164.071
1158.043
1151.559
1146.865
1145.473
1141.365
1135.435
1134.903
1132.298
1123.746
1114.897
1109.738
1106.434
1100.033
1096.673
1092.139
1088.756
1084.235
1080.749
1077.645
1075.114
1068.768
1063.625
1053.790
1046.403
1044.708
1037.028
976.744
968.319
966.704
965.084
963.474
961.852
844.098
831.949
826.563
817.362
814.139
809.242
806.771
801.061
798.804
793.759
789.354
786.317
782.003
777.226
774.772
770.099
762.898
758.299
750.918
682.136
677.949
674.814
667.457
477.817
470.387
462.761
455.246
447.751
445.332
437.115
429.752
422.581
397.429
392.794
389.731
386.707
382.870
374.293
357.736
351.026
O
HO OHOH
HO
+O
OH
OHHO
HO
OH
NH(CH2)5CO2MeOHNH(CH2)5CO2Me
25a 25b
S11
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-deoxy-αααα-D-galacto-hept-2-ulopyranose (25a) and –furanose (25b) 13C, 75 MHz, MeOH-d4
PPM 94 90 86 82 78 74 70 66 62 58 54 50 46 42 38 34 30
98.1357
82.7965
72.8413
72.7558
72.3858
72.2527
71.5905
71.2552
62.9407
56.0206
52.0818
50.8334
49.9336
49.6501
49.3669
49.2446
49.2271
49.0835
48.9725
48.9426
48.9108
48.8001
48.6027
48.5165
48.2327
34.7830
34.7268
34.5847
30.8513
30.0324
27.8497
27.7432
27.2044
O
HO OHOH
HO
+O
OH
OHHO
HO
OH
NH(CH2)5CO2MeOHNH(CH2)5CO2Me
25a 25b
S12
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-galacto-hept-2-ulopyranose (27a) and –furanose (27b) 1H,
300 MHz, MeOH-d4
1209.074
1203.173
1200.984
1197.094
1188.316
1178.793
1164.221
1156.802
1154.614
1151.649
1146.989
1144.388
1141.662
1136.457
1125.979
1119.994
1114.475
1106.146
1094.919
1089.569
1082.517
1078.919
1041.105
1031.354
1014.281
1005.701
1004.175
1002.576
1001.043
999.365
995.076
992.053
985.416
978.506
973.733
966.557
718.663
711.301
703.909
517.920
510.577
502.938
495.318
492.261
487.868
484.276
476.802
469.813
428.137
420.347
417.218
413.340
411.232
404.060
O
HO OHOH
HOO
N(CH2)5CO2Me
O O
OHHO
HOOH
O
N(CH2)5CO2Me
O+
27a 27b
S13
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-galacto-hept-2-ulopyranose (27a) and –furanose (27b) 13C,
75 MHz, MeOH-d4
158.4327
107.3300
104.5388
83.5874
80.2180
75.7478
74.5850
73.7381
71.9974
70.9399
70.7626
63.7771
62.4642
53.4506
52.2688
52.1090
49.9369
49.6532
49.5554
49.5214
49.5119
49.3695
49.2434
49.0857
48.9562
48.8019
48.5182
48.2344
44.3162
44.2806
34.6911
34.6707
27.8660
27.8133
O
HO OHOH
HOO
N(CH2)5CO2Me
O O
OHHO
HOOH
O
N(CH2)5CO2Me
O+
27a 27b
S14
D-glycero-D-galacto/D-talo-heptopyranose 19a and 19b 1H, 300 MHz, D2O
0.998
0.210
0.426
1.085
0.561
PPM 5.00 4.90 4.80 4.70 4.60 4.50 4.40 4.30 4.20 4.10 4.00 3.90 3.80 3.70 3.60 3.50 3.40 3.30
1547.598
1544.241
1540.908
1527.648
1526.612
1442.489
1414.323
1387.527
1386.685
1347.318
1339.480
1216.254
1213.990
1200.682
1197.624
1179.115
1178.627
1175.686
1154.508
1152.633
1151.650
1148.361
1144.496
1138.511
1135.808
1130.433
1123.258
1119.697
1116.049
1113.075
1110.197
1107.281
1096.204
1094.160
1092.272
1091.985
1086.833
1082.104
1076.586
1073.317
1069.876
1063.527
1060.035
1058.110
1051.468
1045.584
1044.056
1036.937
1028.938
1021.432
1019.608
1011.658
O
HOOH
HOOH
OH
OH
19 a and b
S15
D-glycero-D-galacto/D-talo-heptopyranose 19a and 19b 13C, 75 MHz, D2O
PPM 95 93 91 89 87 85 83 81 79 77 75 73 71 69 67 65 63
96.5901
94.0323
92.3434
73.5459
73.0332
71.8321
70.2277
69.4353
69.0700
69.0108
68.7756
68.3358
68.2776
67.7764
63.0065
62.9408
62.7957
O
HOOH
HOOH
OH
OH
19 a and b
S16
1-(N,N-Dibenzylamino)-1-deoxy-αααα-D-manno-hept-2-ulopyranose (28) 1H, 300 MHz, MeOH-d4
PPM 7.2 7.0 6.8 6.6 6.4 6.2 6.0 5.8 5.6 5.4 5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 3.2 3.0 2.8
7.3117
7.2981
7.2849
7.2694
7.2607
7.2535
7.2417
4.9875
4.1538
3.9524
3.9083
3.8419
3.8318
3.8072
3.8003
3.7891
3.7852
3.7750
3.7558
3.7405
3.7363
3.7192
3.7047
3.6874
3.6742
3.6576
3.6299
3.6089
3.4749
3.4646
3.3772
3.3494
3.3438
3.3384
3.3330
3.3277
3.1409
2.9534
2.9079
2.7924
3.9524
3.9083
3.8419
3.8318
3.8072
3.8003
3.7891
3.7852
3.7750
3.7558
3.7405
3.7363
3.7192
3.7047
3.6874
3.6742
3.6576
3.6299
3.6089
3.4749
3.4646
3.3772
3.3494
3.3438
3.3384
3.3330
3.3277
3.1409
2.9534
2.9079
2.7924
2.7469
O
HO OHOH
HOOH
NBn2
28
S17
1-(N,N-Dibenzylamino)-1-deoxy-αααα-D-manno-hept-2-ulopyranose (28) 13C, 75 MHz, MeOH-d4
PPM 130 126 122 118 114 110 106 102 98 94 90 86 82 78 74 70 66 62 58 54
O
HO OHOH
HOOH
NBn2
28
S18
1-(N-(6-Hydroxyhexyl)amino)-1-deoxy-αααα-D-manno-hept-2-ulose (29) 1H, 300 MHz, MeOH-d4
PPM 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4
1160.203
1144.939
1139.824
1134.258
1131.942
1127.217
1122.230
1120.808
1110.331
1101.331
1091.555
1083.897
1077.573
1071.130
1014.327
1005.893
1004.232
1002.594
1000.977
959.076
946.449
943.509
920.365
914.160
911.403
905.002
584.160
526.378
520.324
482.602
476.407
470.073
434.044
O
HO OHOH
HOOH
NH(CH2)6OH
29
S19
1-(N-(6-Hydroxyhexyl)amino)-1-deoxy-αααα-D-manno-hept-2-ulose (29) 13C, 75 MHz, MeOH-d4
PPM 92 88 84 80 76 72 68 64 60 56 52 48 44 40 36 32 28
96.2945
75.2374
74.5608
72.5739
67.8860
62.7335
62.5568
54.9609
49.9284
49.6457
49.4290
49.3620
49.0783
48.7945
48.5107
48.2270
33.3555
27.4662
26.7746
O
HO OHOH
HOOH
NH(CH2)6OH
29
S20
1-(N-(6-Hydroxyhexyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-manno-pyranose (30) 1H, 300 MHz, MeOH-d4
PPM 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4 1.2
1135.944
1132.591
1123.688
1118.488
1115.041
1109.512
1103.113
1093.824
1088.328
1086.477
1083.999
1082.009
1073.630
1067.180
1060.605
1052.888
1048.141
1037.629
1030.995
1005.775
995.830
994.192
992.550
990.948
984.772
977.902
971.018
964.128
490.147
482.941
475.931
469.374
463.389
456.965
450.631
432.454
409.861
406.780
384.245
381.460
O
HO OH
OH
HOO
N(CH2)6OH
O
30
S21
1-(N-(6-Hydroxyhexyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-manno-pyranose (30) 13C, 75 MHz, MeOH-d4
PPM 96 92 88 84 80 76 72 68 64 60 56 52 48 44 40 36 32 28
77.0664
73.1480
72.5916
67.2968
62.9295
62.2666
54.4060
50.0208
49.7376
49.6397
49.6213
49.5787
49.4534
49.1691
48.8849
48.6006
48.3165
44.7134
33.4872
33.4262
28.1206
27.3783
O
HO OH
OH
HOO
N(CH2)6OH
O
30
S22
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-deoxy-αααα-D-manno-hept-2-ulopyranose (31) 1H, 300 MHz, MeOH-d4
PPM 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6
1160.974
1148.400
1143.530
1134.517
1127.027
1125.312
1122.383
1107.074
1020.210
1014.302
1007.867
1005.956
1004.256
1002.667
1001.080
999.583
982.065
974.742
967.427
960.318
950.326
926.973
918.564
911.408
887.759
727.487
720.200
712.904
587.273
537.352
531.905
524.135
516.924
509.446
501.905
494.579
447.801
439.720
432.590
427.166
O
HO OHOH
HOOH
N(CH2)5CO2Me
31
S23
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-deoxy-αααα-D-manno-hept-2-ulopyranose (31) 13C, 75 MHz, MeOH-d4
PPM 160 150 140 130 120 110 100 90 80 70 60 50 40 30
175.6750
96.1593
96.1185
96.0809
75.2168
74.6578
72.5274
67.7863
62.4682
55.0595
52.1316
49.9290
49.6454
49.5471
49.3617
49.2889
49.2646
49.1894
49.0780
48.9106
48.7942
48.6080
48.5104
48.2265
47.7365
40.5798
34.4457
28.2792
27.0513
26.9482
O
HO OH
OH
HOOH
N(CH2)5CO2Me
31
S24
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-manno-hept-2-ulopyranose (32) 1H, 300 MHz, MeOH-d4
PPM 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4
1156.606
1148.819
1138.399
1135.440
1130.294
1127.318
1119.204
1113.000
1106.301
1083.896
1047.429
1037.041
1014.355
1006.149
1004.283
1002.685
1001.059
999.459
996.297
992.403
989.644
985.475
978.512
943.362
720.315
712.989
705.646
511.973
504.269
496.690
493.084
489.430
485.234
477.831
470.799
427.939
422.310
419.479
415.949
412.685
407.442
O
HO OH
OH
HOO
N(CH2)5COOMe
O
32
S25
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-1-N,2-O-carbonyl-1-deoxy-ββββ-D-manno-hept-2-ulopyranose (32) 13C, 75 MHz, MeOH-d4
PPM 160 150 140 130 120 110 100 90 80 70 60 50 40 30
175.8586
158.0638
103.7579
77.2452
73.2462
72.6996
67.4647
62.5605
54.3404
52.1021
49.9454
49.6617
49.3779
49.2613
49.1979
49.0941
48.9593
48.9270
48.8104
48.5267
48.2430
44.5138
34.6467
27.8596
27.0334
O
HO OH
OH
HOO
N(CH2)5COOMe
O
32
S26
1-(N,N-Dibenzylamino)-3-acetamino-1,2-dideoxy-αααα,D-gluco-hept-2-ulopyranose (33a) and –furanose (33b) 1H, 300 MHz, MeOH-d4
6.878
3.453
2.187
3.258
3.310
2.998
PPM 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6
1261.565
1251.431
1238.245
1161.676
1159.198
1156.959
1153.918
1150.890
1147.098
1144.648
1141.504
1139.153
1136.728
1131.452
1124.805
1119.977
1116.538
1109.940
1105.292
1102.976
1096.994
1095.759
1088.516
1086.835
1081.551
1039.473
1032.723
1019.761
1014.335
1005.927
1004.299
1002.705
1001.103
999.558
794.470
788.681
779.840
616.810
606.557
602.918
596.561
488.684
O
HO NHAcOH
HOOH
NBn2 O
OH
NHAcHO
HOOH
NBn2
33a 33b
+
S27
1-(N,N-Dibenzylamino)-3-acetamino-1,2-dideoxy-αααα,D-gluco-hept-2-ulopyranose (33a) and –furanose (33b) 13C, 75 MHz, MeOH-d4
PPM 160 150 140 130 120 110 100 90 80 70 60 50 40 30
141.0437
140.1024
132.8707
131.1222
130.6504
130.5260
130.3568
130.2496
129.6439
129.3361
128.4955
128.0596
98.2584
74.4304
73.8244
72.2186
62.9686
60.4703
57.4311
56.5703
56.4964
51.9922
50.0730
49.7896
49.5062
49.2226
48.9390
48.6553
48.3715
40.5470
23.0481
O
HO NHAcOH
HOOH
NBn2 O
OH
NHAcHO
HOOH
NBn2
33a 33b
+
S28
1-(N-(6-Hydroxyhexyl)amino)-3-acetamino-1,2-dideoxy-αααα-D-gluco-hept-2-ulopyranose (34) 1H, 300 MHz, MeOH-d4
4.582
4.542
3.251
1.036
1.876
1.083
1.000
2.508
5.062
PPM 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4
1137.754
1134.054
1126.090
1123.520
1081.679
1075.235
1068.698
1053.241
1051.027
1044.305
1037.825
1035.403
1014.285
1005.820
1004.221
1002.617
1001.021
999.443
845.325
833.030
808.663
801.276
793.897
788.383
776.060
657.238
615.969
578.858
474.161
468.656
426.542
423.404
420.085
O
HO NHAcOH
HOOH
NH(CH2)6OH
34
S29
1-(N-(6-Hydroxyhexyl)amino)-3-acetamino-1,2-dideoxy-αααα-D-gluco-hept-2-ulopyranose (34) 13C, 75 MHz, MeOH-d4
PPM 160 150 140 130 120 110 100 90 80 70 60 50 40 30
98.1194
74.1611
73.4722
71.7321
62.9173
62.5114
56.0525
55.9567
50.8665
49.9719
49.6889
49.4053
49.1216
48.8379
48.5541
48.2704
33.5839
29.9953
28.0400
26.8168
22.7352
O
HO NHAcOH
HOOH
NH(CH2)6OH
34
S30
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-2-acetamino-1,2-dideoxy-αααα-D-gluco-hept-2-ulopyranose (35) 1H, 300 MHz, MeOH-d4
0.995
1.144
4.150
2.809
3.517
4.224
2.334
4.687
2.313
PPM 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6
O
HO NHAcOH
HOOH
NH(CH2)5COOMe
35
S31
1-(N-(5-(Methoxycarbonyl)pentyl)amino)-2-acetamino-1,2-dideoxy-αααα-D-gluco-hept-2-ulopyranose (35) 13C, 75 MHz, MeOH-d4
PPM 94 90 86 82 78 74 70 66 62 58 54 50 46 42 38 34 30 26
96.7466
74.5095
72.1755
71.4365
61.7013
56.0322
54.1367
52.1093
49.9016
49.7566
49.6179
49.5241
49.4712
49.3341
49.1933
49.0503
48.8933
48.7665
48.6175
48.4827
48.1990
34.4281
26.9674
26.7453
25.4152
22.5047
O
HO NHAcOH
HOOH
NH(CH2)5COOMe
35
S32
1-N-[(5S)-(tert-Butoxylcarbonylamino)-5-(methoxycarbonyl)pentyl]amino-3-acetamino-1,2-dideoxy-αααα-D-gluco-hept-2-ulopyranose (36) 1H, 300 MHz, MeOH-d4
PPM 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6 2.4 2.2 2.0 1.8 1.6 1.4
4.1320
4.1206
4.1050
3.8225
3.7814
3.7748
3.7647
3.7546
3.7406
3.6926
3.6708
3.6472
3.6238
3.6004
3.5017
3.4733
3.4442
3.3769
3.3489
3.3435
3.3381
3.3328
3.3274
2.7649
2.7240
2.6351
2.6121
2.5884
2.5457
2.5088
2.5061
2.0858
2.0497
1.8337
1.8220
1.7974
1.7802
1.7548
1.7457
1.7166
1.6948
1.6687
1.6510
1.6398
1.6201
1.5934
1.5700
1.5465
1.5288
O
HO NHAcOH
HOOH
NH(CH2)4O
OMe
NH O
O
36
S33
1-N-[(5S)-(tert-Butoxylcarbonylamino)-5-(methoxycarbonyl)pentyl]amino-3-acetamino-1,2-dideoxy-αααα-D-gluco-hept-2-ulopyranose (36) 13C, 75 MHz, MeOH-d4
PPM 160 150 140 130 120 110 100 90 80 70 60 50 40 30
174.1236
158.1771
98.3104
98.2767
80.6013
74.1004
73.6651
71.7705
62.6079
58.3844
56.2606
56.0407
55.8650
55.0858
54.9977
52.6748
50.7030
49.9598
49.6760
49.3922
49.2238
49.1084
48.9412
48.8246
48.6238
48.5410
48.2574
32.4966
29.9187
28.8213
24.5289
22.7436
O
HO NHAcOH
HOOH
NH(CH2)4O
OMe
NH O
O
36