S1
Supporting Information
Aryl H-phosphonates 17. (N-Aryl)phosphoramidates of pyrimidine nucleoside analogues – synthesis,
selected properties and anti-HIV activity.
Joanna Romanowskaa, Michał Sobkowski
a, Agnieszka Szymańska-Michalak
a, Krystian Kołodziej
a, Aleksandra Dąbrowska
b Andrzej Lipniacki
b Andrzej
Piasekb, Zofia M. Pietrusiewicz
a, Marek Figlerowicz
a,c, Andrzej Guranowski
d, Jerzy Boryski
a, Jacek Stawiński
a and Adam Kraszewski
a
a-Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
b-National Institute of Medicines, Chełmska 30/34, 00-725 Warsaw, Poland.
c-Institute of Computing Science, Poznań University of Technology, Piotrowo 2, 60-965 Poznań, Poland
d-Life Science University, Faculty of Biochemistry and Biotechnology, Wołyńska 35, 60-637 Poznań, Poland
Contents
3’-Azido-3’-deoxythymidyn-5’-yl (N-phenyl)phosphoramidate, triethylammonium salt. 4aa ........................................................................................... S2
3’-Azido-3’-deoxythymidyn-5’-yl (N-4-methylphenyl)phosphoramidate, triethylammonium salt. 4ab ............................................................................ S5
3’-Azido-3’-deoxythymidyn-5’-yl (N-4-chlorophenyl)phosphoramidate, triethylammonium salt. 4ac ............................................................................. S8
3’-Azido-3’-deoxythymidin-5’-yl [N-(pyridin-2-yl)]phosphoramidate. 4ad .................................................................................................................... S11
3’-Azido-3’-deoxythymidin-5’-yl [N-(pyridin-3-yl)]phosphoramidate. 4ae ..................................................................................................................... S14
3’-Azido-3’-deoxythymidin-5’-yl [N-(pyridin-4-yl)]phosphoramidate. 4af ...................................................................................................................... S17
2’,3’-Dideoxyuridin-5’-yl [N-(pyridin-2-yl)]phosphoramidate. 4bd ................................................................................................................................. S20
2’,3’-Dideoxyuridin-5’-yl [N-(pyridin-3-yl)]phosphoramidate. 4be ................................................................................................................................. S23
2’,3’-Dideoxyuridin-5’-yl [N-(pyridin-4-yl)]phosphoramidate. 4bf .................................................................................................................................. S26
Di(1H-1,2,4-triazol-1-yl) [N-(pyridin-4-yl)]phosphoramidate 6 ........................................................................................................................................ S29
S2
Compound 4aa, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.26
1.28
1.30
1.87
2.41
2.42
2.44
3.16
3.18
3.20
3.22
4.00
4.01
4.03
4.05
4.06
4.07
4.10
4.10
4.11
4.11
4.29
4.31
4.32
4.33
4.80
6.13
6.14
6.16
6.84
6.86
6.88
7.00
7.01
7.17
7.19
7.21
7.58
0.57
6.04
0.23
3.04
0.09
2.10
4.01
0.31
0.28
3.10
1.07
1.09
0.11
1.00
2.02
2.05
0.22
1.01
S3
Compound 4aa, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
7.8
11.2
11.4
16.3
35.6
46.2
57.0
60.0
63.8
63.9
82.6
82.7
84.6
110.9
116.3
116.4
119.8
128.6
137.0
141.5
151.0
165.9
S4
Compound 4aa, 31
P NMR, DMSO
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-1.72
0.00
25.73
1.00
S5
Compound 4ab, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.27
1.29
1.30
1.85
1.85
2.19
2.40
2.42
2.43
3.17
3.19
3.20
3.22
3.37
3.41
3.42
3.44
3.46
3.97
3.98
3.98
4.00
4.01
4.01
4.02
4.03
4.04
4.05
4.06
4.06
4.08
4.08
4.09
4.10
4.10
4.11
4.28
4.30
4.31
4.32
4.80
5.05
6.14
6.15
6.17
6.90
6.92
6.98
7.00
7.54
7.54
0.14
0.30
1.00
13.93
1.91
0.11
0.08
2.97
0.22
0.09
0.12
0.06
0.12
3.01
1.98
0.21
0.04
0.20
8.75
0.17
1.05
1.52
3.36
1.03
0.09
0.49
0.05
1.07
2.01
2.05
0.36
0.22
1.00
0.07
S6
Compound 4ab, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
6.5
7.9
8.2
8.4
11.6
11.6
19.5
23.7
35.9
46.6
48.8
52.1
60.4
62.0
64.2
64.2
82.9
83.0
84.9
111.2
111.4
117.0
117.1
120.1
124.4
129.2
129.7
137.3
139.2
151.4
166.1
S7
Compound 4ab, 31
P NMR, DMSO
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-1.38
95.40
0.50
0.76
3.38
S8
Compound 4ac, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.28
1.30
1.31
1.84
2.47
2.48
2.50
3.19
3.21
3.22
3.24
3.98
3.99
4.01
4.02
4.03
4.09
4.10
4.10
4.12
4.13
4.13
4.34
4.35
4.37
4.38
4.80
6.15
6.17
6.19
6.93
6.96
7.12
7.14
7.45
7.45
10.30
0.26
0.26
2.85
0.28
2.05
6.64
0.23
0.95
2.10
1.00
0.08
1.00
1.89
1.92
1.48
S9
Compound 4ac, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
6.1
7.8
11.2
35.4
46.2
51.7
59.8
64.0
64.1
82.5
82.6
84.7
110.9
117.8
117.9
123.8
128.0
137.0
140.3
151.0
165.7
S10
Compound 4ac, 31
P NMR, DMSO (with H3PO4 ext. standard)
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-2.13
-0.00
44.79
1.00
S11
Compound 4ad, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.18
1.19
1.27
1.29
1.31
1.84
1.93
2.48
2.49
2.51
2.52
3.18
3.20
3.22
3.23
3.37
4.02
4.03
4.05
4.06
4.08
4.13
4.14
4.16
4.17
4.17
4.37
4.38
4.40
4.41
4.80
6.16
6.17
6.19
6.85
6.87
6.87
6.87
6.89
7.02
7.04
7.51
7.57
7.58
7.59
7.61
7.62
8.03
8.04
1.52
1.51
3.03
0.15
2.08
0.97
0.96
1.29
2.10
1.02
9.50
1.01
1.01
1.00
1.01
1.03
1.00
S12
Compound 4ad, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
8.1
11.5
35.8
46.6
60.1
64.5
64.6
82.7
82.8
85.0
110.9
111.2
116.4
137.3
138.6
147.0
151.5
154.0
154.1
166.4
S13
Compound 4ad, 31
P NMR, DMSO
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-4.47
82.71
1.00
S14
Compound 4ae, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.18
1.19
1.29
1.82
2.47
2.48
2.49
2.49
2.50
2.51
4.00
4.01
4.02
4.04
4.05
4.11
4.12
4.13
4.14
4.15
4.34
4.35
4.37
4.38
4.80
6.15
6.17
6.18
7.20
7.21
7.22
7.23
7.43
7.44
7.44
7.44
7.45
7.46
7.46
7.46
7.48
7.48
7.96
7.97
8.18
8.19
0.20
0.21
2.95
0.06
1.99
0.05
0.02
1.01
2.01
1.01
7.33
1.00
1.02
0.98
1.01
0.98
1.00
S15
Compound 4ae, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
8.1
11.4
11.4
35.7
46.6
60.0
64.6
64.7
82.6
82.7
85.2
111.1
125.9
129.5
129.6
132.1
132.1
134.9
137.5
141.5
151.3
166.1
S16
Compound 4ae, 31
P NMR, DMSO
-20-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-2.17
80.95
1.00
S17
Compound 4af, 1H NMR, D2O
S18
Compound 4af, 13
C NMR, D2O
S19
Compound 4af, 31
P NMR, DMSO
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-4.43
S20
Compound 4bd, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.91
1.92
1.93
1.94
1.94
1.97
2.08
2.09
2.10
2.11
2.12
2.12
2.13
2.14
2.14
2.15
2.16
2.16
2.17
2.41
2.43
2.44
2.44
2.45
2.45
2.46
2.47
2.47
2.49
2.51
3.97
3.99
4.00
4.02
4.03
4.18
4.18
4.19
4.19
4.20
4.21
4.22
4.22
4.33
4.35
4.36
4.37
4.38
4.80
5.72
5.74
6.04
6.05
6.06
6.07
7.08
7.10
7.11
7.19
7.21
7.71
7.74
7.94
7.94
7.96
7.98
7.98
8.05
8.06
8.07
0.04
0.08
1.07
2.18
1.12
0.08
1.07
1.05
0.04
1.11
0.94
0.08
0.97
0.10
0.98
1.00
1.02
1.08
1.00
S21
Compound 4bd, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
24.4
30.1
66.1
66.1
79.6
79.7
85.8
101.2
113.6
113.7
115.6
139.0
141.6
141.6
143.2
151.0
151.7
151.7
165.6
S22
Compound 4bd, 31
P NMR, DMSO (with H3PO4 ext. standard)
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-3.82
0.00
95.00
2.85
2.16
S23
Compound 4be, 1H NMR, D2O
11 10 9 8 7 6 5 4 3 2 1 0 ppm
1.84
1.86
1.87
1.88
1.89
1.91
1.92
1.94
2.07
2.08
2.09
2.10
2.10
2.11
2.12
2.13
2.14
2.15
2.16
2.39
2.41
2.42
2.43
2.43
2.44
2.44
2.45
2.46
2.47
2.49
3.33
3.90
3.91
3.93
3.94
3.96
4.11
4.11
4.12
4.13
4.14
4.15
4.34
4.36
4.36
4.37
5.63
5.65
6.04
6.05
6.06
6.07
7.36
7.37
7.38
7.39
7.59
7.59
7.59
7.60
7.61
7.61
7.61
7.62
7.67
7.69
8.02
8.04
8.22
8.23
0.22
1.10
2.07
0.18
1.16
0.02
0.05
0.32
1.04
0.16
0.21
1.06
0.14
1.05
13.74
0.98
0.11
1.00
0.12
1.11
1.11
1.03
0.15
0.09
0.13
1.11
1.14
S24
Compound 4be, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
24.5
30.3
65.6
65.7
79.7
79.8
86.0
101.1
124.4
126.1
126.2
135.1
135.2
137.7
139.7
141.5
151.0
165.7
S25
Compound 4be, 31
P NMR, DMSO (with H3PO4 ext. standard)
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-2.50
0.00
S26
Compound 4bf, 1H NMR, D2O
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5 ppm
1.86
1.88
1.89
1.91
1.92
1.93
1.94
1.96
2.07
2.08
2.09
2.10
2.11
2.12
2.13
2.14
2.15
2.16
2.17
2.39
2.42
2.43
2.43
2.44
2.45
2.45
2.47
2.49
3.33
3.90
3.92
3.93
3.94
3.96
4.11
4.12
4.12
4.14
4.14
4.15
4.36
4.36
4.37
4.80
5.67
5.69
6.04
6.04
6.05
6.06
7.04
7.06
7.68
7.70
8.16
8.18
1.15
2.21
0.07
1.16
0.13
1.00
0.15
1.21
0.15
1.12
0.98
0.10
0.97
0.19
1.97
0.09
1.04
0.11
2.00
0.11
S27
Compound 4bf, 13
C NMR, D2O
210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
24.8
30.7
66.1
66.1
80.1
80.2
86.4
101.5
112.0
112.1
141.9
146.6
151.8
152.2
166.6
S28
Compound 4bf, 31
P NMR, DMSO (with H3PO4 ext. standard)
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-4.29
0.00
S29
Compound 6, 1H NMR, DMSO-d6
14 13 12 11 10 9 8 7 6 5 4 3 2 1 ppm
1.15
1.17
1.19
2.50
2.50
3.07
3.09
3.10
3.12
3.35
3.56
6.94
6.96
7.95
8.12
8.13
8.14
8.62
9.03
13.22
0.20
1.83
0.24
0.85
0.49
0.06
2.17
0.14
0.16
0.14
2.99
1.24
0.26
0.10
0.01
0.17
0.08
0.06
0.03
0.02
2.00
0.02
0.08
1.10
S30
Compound 6, 31
P NMR, DMSO
-10140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 ppm
-21.82
-16.31
-15.04
-14.50
0.02
0.08
0.04
1.00
![Formation of 2,4,5-triaryl-4,5-dihydro-1 H-imidazoles, ( 1), from aryl aldehydes. Crystal structures of cis-( 1: aryl = pyridin-2-yl), { trans-[( 1: aryl = pyridin-2-yl)H] +[OAc] −·3H](https://cdn.vdocuments.mx/doc/165x107/631c0397665120b3330ba5c0/formation-of-245-triaryl-45-dihydro-1-h-imidazoles-1-from-aryl-aldehydes.jpg)
