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TRANSCRIPT
Synthesis and biological evaluation of aryl phosphoramidate prodrugs of
fosfoxacin and its derivatives
Mathilde Munier, Denis Tritsch, Didier Lièvremont, Michel Rohmer, Catherine Grosdemange-Billiard*
Laboratoire Chimie et Biochimie de Molécules Bioactives – Université de Strasbourg/CNRS, UMR 7177,
Institut Le Bel, 4 rue Blaise Pascal, 67081 Strasbourg, France
* Corresponding author: Tel.: +33-368-851-349; e-mail: [email protected]
Table of contents
Fig. S1 Stability of the prodrugs 8-16 in buffer (TEOA) 3
Fig. S2 Carboxypeptidase Y mediated cleavage of prodrug 8a, monitored by 31P NMR 4
Fig. S3 Carboxypeptidase Y mediated cleavage of prodrug 16a, monitored by 31P NMR. 5
Fig. S4 Carboxypeptidase Y mediated cleavage of prodrug 16b, monitored by 31P NMR. 6
Fig. S5 Carboxypeptidase Y mediated cleavage of prodrug 8b, monitored by 31P NMR. 7
Fig. S6 Stability of 8a in M. smegmatis and E. coli supernatants. 8
Fig. S7 Stability of 8b in M. smegmatis and E. coli supernatants. 9
Fig. S8 Esterase and phosphatase activities in M. smegmatis crude cell free system tested on 8a 10
Fig. S9 Esterase and phosphatase activities in E. coli crude cell free system tested on 8a 11Fig. S10 Esterase and phosphatase activities in M. smegmatis crude cell free system tested on 8a 12
Fig. S11 Esterase and phosphatase activities in E. coli crude cell free system tested on 8a 13
1H -NMR (400 MHz, CDCl3) : 8a 14
13C -NMR (125.8 MHz, CDCl3) : 8a 15
31P-NMR (162.05MHz, CDCl3) : 8a 16
Mass spectroscopy : 8a 17
1H -NMR (400 MHz, CDCl3) : 8b 18
13C -NMR (125.8 MHz, CDCl3) : 8b 19
1
31P-NMR (162.0 MHz, CDCl3) : 8b 20
Mass spectroscopy : 8b 21
1H -NMR (400 MHz, CDCl3) : 16a 22
13C -NMR (125.8 MHz, CDCl3) : 16a 23
31P-NMR (162.0 MHz, CDCl33) : 16a 24
Mass spectroscopy : 16a 25
1H -NMR (300 MHz, CDCl3) : 16b 26
13C -NMR (125.8 MHz, CDCl3) : 16b 27
31P -NMR (162.0 MHz, CDCl3) : 16b 28
Mass spectroscopy : 16b 29
2
Fig. S1
3
Fig. S2
4
Fig. S3
5
Fig. S4
6
Fig. S5
7
Fig. S6
8
Fig. S7
9
Fig. S8
10
Fig. S9
11
Fig. S10
12
Fig. S11
13
1H-NMR (400 MHz, CDCl3) : 8a
14
13C-NMR (125.8 MHz, CDCl3) : 8a
15
31P-NMR (162.0 MHz, CDCl3) : 8a
16
Masse speectroscopy : 8a
17
1H-NMR (400 MHz, CDCl3) : 8b
18
13C-NMR (125.8 MHz, CDCl3) : 8b
19
31P-NMR (162.0 MHz, CDCl3) : 8b
20
Masse speectroscopy : 8b
21
1H-NMR (400 MHz, CDCl3) : 16a
22
13C-NMR (125.8 MHz, CDCl3) : 16a
23
31P-NMR (162.0 MHz, CDCl3) : 16a
24
Masse speectroscopy : 16a
25
1H-NMR (400 MHz, CDCl3) : 16b
26
13C-NMR (125.8 MHz, CDCl3) : 16b
27
31P-NMR (162.0 MHz, CDCl3) : 16b
28
Masse speectroscopy : 16b
29