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TRANSCRIPT
Thieme
Supporting Information for DOI: 10.1055/s-0035-15 2727
© Georg Thieme Verlag KG Stuttgart · New York 201
S1
Supporting Information
Multicomponent Domino Synthesis and Antibacterial Activity of
Neomycin-Sugar Conjugates
Aurora Sganappa, Maria Cristina Bellucci, Victor Nizet, Yitzhak Tor,* Alessandro
Volonterio*
Department of Chemistry, Materials, and Chemical Engineer “G. Natta”, Politecnico di
Milano, via Mancinelli 7, 20131 Milano, Italy; Department of Food, Environmental and
Nutritional Sciences, Università degli Studi di Milano, via Celoria 2, 20133 Milano, Italy;
Department of Chemistry and Biochemistry, Department of Pediatrics and Skaggs School
of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500
Gilman Drive, La Jolla, California 92093, United States.
[email protected]; [email protected]
Table of Contents:
Pages S2-S11 1H NMR, and 13C NMR, spectra of all new compounds
S2
1.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
300
1.34
71.
354
1.43
71.
451
1.46
3
1.76
31.
779
1.96
92.
007
2.03
72.
045
2.04
9
2.88
52.
891
3.12
03.
125
3.14
1
3.47
63.
581
3.77
8
3.91
84.
117
4.12
14.
126
4.15
74.
267
4.26
7
4.65
24.
658
4.67
74.
904
4.94
05.
011
5.10
85.
146
5.15
15.
254
5.26
05.
328
5.60
65.
619
7.35
8
2030405060708090100110120130140150160170f1 (ppm)
0
500
1000
1500
2000
2500
17.8
617
.99
18.0
818
.14
25.9
626
.07
26.1
626
.17
26.2
726
.35
27.0
027
.11
27.5
627
.66
29.8
632
.87
32.9
9
49.3
649
.47
50.8
654
.21
54.8
6
60.2
864
.84
64.8
965
.80
66.2
567
.01
67.1
768
.79
70.0
870
.16
70.5
971
.47
71.7
372
.78
76.6
877
.58
77.8
577
.97
79.8
998
.98
99.1
999
.28
120.
18
126.
4012
6.50
126.
5312
6.58
126.
6212
6.70
126.
8213
4.58
155.
0115
5.33
155.
3815
5.69
156.
12
168.
4216
8.79
169.
4416
9.69
169.
7817
0.01
170.
11
O
O OHO
O
OH
ONHBoc
NHBoc
OBocHN
OH NHBoc
BocHN
NHBocHO
HO
HO
S
NHN
O
O
AcOO
AcO
OAcAcO
NHO COOBn
6a
S3
1.52.02.53.03.54.04.55.05.56.06.57.07.5f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
1.34
11.
346
1.39
41.
478
1.48
41.
494
1.50
6
1.79
51.
812
1.95
51.
962
2.02
22.
044
2.04
92.
088
2.09
6
2.77
22.
929
2.94
2
3.14
7
3.34
73.
351
3.58
13.
605
3.82
33.
941
3.95
33.
960
4.15
24.
293
4.29
74.
305
4.67
5
4.89
34.
985
5.01
15.
018
5.20
6
5.35
9
7.39
4
2030405060708090100110120130140150160170f1 (ppm)
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000av-asv 310 A MeOD.2.fid
11.7
417
.87
18.0
620
.09
20.2
420
.30
26.0
926
.18
26.2
226
.38
27.0
527
.14
27.2
627
.55
27.6
928
.49
29.8
932
.67
32.9
433
.11
35.4
736
.96
37.5
139
.04
40.0
341
.50
49.3
852
.69
55.0
760
.59
64.9
665
.66
65.7
466
.54
67.5
367
.67
68.9
170
.24
70.3
470
.70
71.4
371
.61
71.8
572
.91
76.6
877
.67
77.9
996
.65
97.9
699
.53
99.6
110
8.28
126.
5412
6.62
126.
85
155.
0515
5.42
155.
7415
6.19
168.
5416
9.16
169.
5616
9.75
170.
65
O
O OHO
O
OH
ONHBoc
NHBoc
OBocHN
OH NHBoc
BocHN
NHBocHO
HO
HO
S
NHN
O
O
AcOO
AcO
NHAcAcO
NHO COOBn
6b
S4
1.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.6f1 (ppm)
-200
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
1800
1900
2000
2100
2200
2300
2400
1.34
31.
436
1.44
71.
459
1.46
8
1.83
51.
962
2.02
72.
065
2.13
4
2.74
5
2.89
5
3.12
6
3.28
0
3.48
5
3.71
53.
729
3.77
93.
919
3.99
64.
016
4.10
84.
115
4.14
04.
239
4.82
2
4.94
35.
116
5.12
35.
160
5.16
35.
168
5.24
15.
246
5.25
15.
273
7.35
8
2030405060708090100110120130140150160170f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
17.9
4618
.030
18.1
0126
.149
26.2
3826
.273
26.4
2727
.075
27.1
2327
.201
27.3
2533
.048
33.1
53
49.3
2154
.235
55.3
9058
.849
61.0
0464
.183
64.8
1065
.002
65.0
5367
.254
68.0
8968
.934
70.2
7370
.726
71.8
7572
.897
76.6
9677
.754
78.0
5680
.083
96.2
21
126.
609
126.
689
126.
888
134.
642
155.
081
155.
441
155.
763
156.
140
168.
796
168.
837
168.
926
169.
728
169.
854
170.
165
O
O OHO
O
OH
ONHBoc
NHBoc
OBocHN
OH NHBoc
BocHN
NHBocHO
HO
HO
S
NHN
O
O
AcO
AcO
AcO
NHO
O
AcOCOOBn
6c
S5
1.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.4f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
1800
1900
2000
00
1.33
91.
439
1.44
31.
454
1.46
61.
755
1.76
91.
776
1.98
32.
003
2.00
82.
012
2.03
12.
063
2.11
5
2.73
6
2.89
6
3.22
23.
226
3.48
2
3.78
1
3.91
8
4.11
14.
137
4.22
64.
247
4.51
74.
523
4.55
24.
651
4.67
14.
784
4.78
84.
808
4.87
54.
944
5.01
95.
043
5.04
35.
110
5.15
95.
289
5.29
75.
313
5.36
35.
368
5.37
35.
379
7.36
4
2030405060708090100110120130140150160170f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
130015.6
217
.79
17.8
918
.00
18.1
018
.15
18.2
218
.42
26.0
726
.19
26.3
727
.00
27.1
127
.65
27.9
329
.92
32.6
733
.00
49.3
650
.93
55.5
960
.40
61.5
364
.93
65.7
266
.19
67.0
967
.16
68.0
768
.96
70.2
170
.88
71.8
272
.23
72.8
773
.88
77.6
577
.97
79.9
6
94.3
9
126.
5212
6.58
126.
6312
6.85
134.
65
155.
0515
5.40
156.
16
168.
4016
8.68
168.
8016
8.98
169.
1816
9.49
O
O OHO
O
OH
ONHBoc
NHBoc
OBocHN
OH NHBoc
BocHN
NHBocHO
HO
HO
S
NHN
O
O
AcOO
AcO
OAc
NHOO
AcO
AcO
OAcAcO
O
COOBn
6d
S6
1.52.02.53.03.54.04.55.05.56.06.57.0.5f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1.29
91.
416
1.43
71.
443
1.45
21.
469
1.48
81.
558
1.61
71.
926
1.95
51.
970
1.97
6
2.25
2
2.72
52.
743
2.75
9
3.07
83.
095
3.11
2
3.33
83.
341
3.48
8
3.70
13.
723
3.89
23.
902
3.90
93.
923
4.10
94.
128
4.23
6
4.85
04.
877
5.12
15.
198
5.32
2
7.36
17.
369
102030405060708090100110120130140150160170180f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
17000
17.9
818
.06
18.1
718
.27
21.3
221
.38
25.9
325
.97
26.0
826
.18
26.2
226
.38
27.0
227
.16
27.9
328
.20
32.6
433
.11
33.5
433
.80
36.7
737
.43
49.2
5 M
eOD
49.4
7 M
eOD
51.5
051
.58
64.8
964
.96
65.2
166
.83
67.4
270
.22
70.7
173
.04
74.0
376
.21
76.6
677
.68
78.0
478
.33
96.7
2
126.
5112
6.55
126.
6012
6.75
126.
8012
6.84
126.
9412
7.12
127.
2412
9.51
130.
2713
0.37
130.
5613
0.94
130.
9613
4.63
154.
7315
4.99
155.
3915
6.15
168.
0016
8.42
168.
9516
9.21
169.
7917
0.23
173.
2317
3.57
O
O OHO
O
OH
ONHBoc
NHBoc
OBocHN
OH NHBoc
BocHN
NHBocHO
HO
HO
S
NHN
O
NHO
O
AcO
BocHN
AcO
O
HN
AcO
AcO
O
NHBoc
NHBoc
COOBn
6e
S7
x TFA
1.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.4.6f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
10.3
5
3.60
1.10
3.68
2.55
1.06
3.16
23.6
6
1.20
4.77
2.40
2.74
2.10
3.17
1.07
1.08
1.00
1.49
8
1.81
51.
847
1.88
0
2.43
5
3.03
93.
076
3.18
83.
191
3.78
13.
788
3.85
83.
970
3.97
53.
998
4.02
84.
052
4.07
64.
184
4.26
14.
358
5.25
35.
257
5.35
25.
352
5.35
8
5.99
46.
004
2030405060708090100110120130140150160170f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
27.2
127
.35
27.9
530
.49
34.5
138
.00
38.4
140
.29
40.5
648
.52
49.6
750
.96
53.6
556
.10
56.3
858
.27
60.9
267
.45
67.6
567
.85
68.0
869
.59
69.8
170
.23
70.7
772
.51
73.2
873
.71
75.0
975
.84
75.9
075
.97
78.7
280
.16
85.5
395
.01
95.6
4
102.
34
110.
47
114.
86
117.
75
158.
8116
2.49
162.
85
170.
77
175.
95
O
O OHO
O
OH
ONH2
NH2
OH2N
OH NH2
H2N
NH2HO
HO
HO
S
NHN
O
O
HO
O
HO
OHHO
NO
O
7a
S8
x TFA
1.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.2f1 (ppm)
-100
0
100
200
300
400
500
600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
7.86
1.66
0.90
1.15
7.35
2.07
1.08
1.18
14.8
4
3.27
1.39
3.42
1.28
1.13
1.57
2.24
2.00
0.94
1.00
0.91
1.51
91.
523
1.73
81.
756
1.87
11.
902
2.45
92.
490
2.67
2
2.85
4
3.06
3
3.23
33.
250
3.26
73.
284
3.67
4
3.81
03.
880
3.97
03.
992
3.99
74.
020
4.05
04.
075
4.20
64.
284
4.37
84.
382
5.27
75.
282
5.38
1
6.01
76.
027
102030405060708090100110120130140150160170180f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
1100021.7
022
.35
22.4
526
.14
27.2
928
.06
28.1
028
.14
28.8
529
.88
30.7
330
.82
34.3
634
.51
34.6
434
.73
38.2
738
.59
38.6
738
.72
38.8
040
.42
40.7
248
.72
49.8
151
.14
53.8
053
.92
55.7
055
.80
55.8
456
.10
56.4
457
.22
58.3
859
.28
60.8
861
.01
61.0
567
.60
67.7
667
.88
68.2
469
.78
70.2
470
.28
70.3
970
.87
70.9
472
.65
73.9
274
.09
74.1
374
.18
75.3
076
.06
76.0
878
.89
78.9
580
.39
85.5
895
.13
95.8
410
1.43
101.
4910
2.12
110.
5311
2.13
115.
0311
7.93
120.
8315
8.98
162.
2116
2.57
162.
9216
3.28
170.
8817
4.65
174.
8817
5.95
176.
01
O
O OHO
O
OH
ONH2
NH2
OH2N
OH NH2
H2N
NH2HO
HO
HO
S
NHN
O
O
HO
O
HO
NHAcHO
NO
O
7b
S9
x TFA
1.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.2f1 (ppm)
-200
0
200
400
600
800
1000
1200
1400
1600
1800
2000
2200
2400
2600
2800
3000
10.4
7
2.37
1.02
1.19
14.2
9
6.81
1.03
1.28
22.7
2
5.90
2.25
2.38
2.14
2.01
1.04
1.00
0.92
1.51
31.
519
1.52
6
1.81
7
1.92
3
2.47
12.
502
3.05
53.
088
3.14
4
3.34
0
3.71
13.
812
3.88
53.
987
4.01
14.
036
4.08
54.
107
4.11
14.
217
4.29
1
5.28
3
5.38
3
6.02
26.
031
102030405060708090100110120130140150160170180f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
1000021.2
026
.27
26.9
227
.08
27.9
527
.98
28.0
430
.60
30.6
931
.57
34.2
334
.30
34.6
034
.65
37.0
438
.32
38.5
638
.67
40.3
740
.62
48.6
449
.74
51.0
653
.74
56.0
156
.20
58.3
461
.04
65.2
465
.38
66.9
367
.53
67.6
568
.13
69.6
870
.23
70.2
870
.84
72.5
472
.78
72.8
573
.78
75.1
378
.81
78.8
580
.19
80.2
785
.52
94.9
895
.70
99.8
799
.98
110.
4311
1.82
114.
7111
7.60
120.
49
158.
5715
8.63
161.
7016
2.06
162.
4216
2.79
164.
9816
5.61
170.
7117
4.89
175.
7517
5.79
O
O OHO
O
OH
ONH2
NH2
OH2N
OH NH2
H2N
NH2HO
HO
HO
S
NHN
O
O
HO
HO
HO
NO
O
O
HO
7c
S10
x TFA
1.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.2f1 (ppm)
0
100
200
300
400
500
600
700
800
900
9.16
3.53
1.06
0.83
5.68
2.29
1.12
32.0
5
2.56
4.38
1.26
1.18
2.07
2.04
3.01
0.96
0.97
1.00
0.87
1.62
9
1.94
51.
945
1.97
52.
007
2.04
0
2.57
12.
602
2.66
3
2.80
22.
860
2.95
9
3.16
6
3.35
3
3.83
13.
918
3.98
74.
076
4.10
04.
106
4.12
64.
155
4.17
94.
203
4.31
74.
390
4.39
44.
483
5.38
85.
431
5.44
15.
484
5.49
0
6.12
06.
130
30405060708090100110120130140150160170180f1 (ppm)
-1000
-500
0
500
1000
1500
2000
2500
3000
3500
4000
4500
5000
5500
6000
6500
7000
7500
27.1
527
.30
27.9
328
.09
30.4
134
.02
34.1
334
.40
38.2
438
.35
38.4
038
.54
40.2
440
.40
40.5
348
.45
48.9
149
.62
50.9
153
.60
58.2
460
.55
60.7
760
.84
67.4
167
.62
67.6
867
.74
67.8
268
.05
69.3
869
.54
69.5
970
.21
70.7
271
.67
72.4
972
.63
72.7
672
.87
72.9
373
.06
73.1
273
.68
74.5
775
.07
76.2
176
.28
76.9
777
.04
78.6
578
.69
85.5
495
.03
95.6
299
.62
99.6
610
2.15
110.
4611
0.51
112.
0011
4.90
115.
0611
7.80
117.
9712
0.70
158.
8215
8.87
162.
3216
2.67
163.
0316
3.38
170.
77
175.
9817
6.06
O
O OHO
O
OH
ONH2
NH2
OH2N
OH NH2
H2N
NH2HO
HO
HO
S
NHN
O
O
HOO
HO
OH
NO
O
O
HO
HO
OHHO
O
7d
S11
1.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.6f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
700
750
800
850
900
13.1
5
3.72
2.26
1.11
4.87
3.18
6.09
4.36
31.3
0
6.90
1.25
2.31
1.99
0.71
1.00
0.81
2.10
1.28
71.
291
1.63
5
1.90
7
2.26
6
2.49
0
2.70
92.
720
2.74
72.
763
3.05
03.
066
3.07
03.
083
3.08
73.
230
3.23
53.
256
3.57
2
3.84
43.
866
4.05
5
4.17
0
4.31
64.
367
4.41
9
5.34
75.
351
5.43
05.
439
5.65
15.
661
102030405060708090100110120130140150160170180f1 (ppm)
-1000
0
1000
2000
3000
4000
5000
6000
7000
8000
9000
10000
11000
12000
13000
14000
15000
16000
21.3
526
.22
26.2
827
.07
27.1
827
.87
28.1
133
.42
33.6
537
.38
38.4
938
.95
39.2
647
.61
48.0
148
.45
MeO
D48
.68
MeO
D50
.25
53.1
366
.36
67.4
967
.56
70.1
770
.52
70.7
370
.82
71.3
571
.44
74.0
978
.65
95.7
595
.81
156.
2415
7.81
168.
6117
2.64
173.
9517
4.17
O
O OHO
O
OH
ONH2
NH2
OH2N
OH NH2
H2N
NH2HO
HO
HO
S
NHN
O
NO
O
O
HO
H2N
HO
O
HN
HO
HO
O
NH2
NH27e