C. Nmr, FT-IR (cm ?1 ): 3314, 1709, 1655. MS/ESI: (M + H) + 253.0790 (m/z) Synthesis of (R)-4-Fluorophenyl-(3-oxoisoxazolidin-4-yl)- carbamate (1d). 1d was obtained as a white crystalline solid in 70% yield, mp 175?176 °C. 1 H NMR (DMSO-d 6 ): 11.54 (bs,1H, D 2 O exchange), = 8.56 Hz); 6.98 (d,2H, J = 8.56 Hz); 4.68?4.63 (m,1H), p.3916

1. , 1. , J. =. 2h, 2. , and J. =. , 8 Hz); 154.1; 147.332 Hz); 116.5; 116.0 (d, J = 227 Hz); 72.0; 53.4. FT-IR (cm ?1 ): 3320, 1712, 1699 Synthesis of (R)-4-Bromophenyl-(3-oxoisoxazolidin-4-yl)- carbamate (1e). 1e was obtained as a white crystalline solid in 75% yield, mp 180?181 °C. 1 H NMR (DMSO-d 6 ): 11.55 (bs,1H, D 2 O exchange)42 (s, 1H, D 2 O exchange) General Procedure for Synthesis of Dicarbamates 2a?f. A 50 mg (0.5 mmol) portion of D-4-amino-3-isoxazolidinone were dissolved in 1.2 mL of aqueous 1 M NaHCO 3 and cooled at 0 °C, and 1.0 mmol of the corresponding chloroformate was added; the solution was stirred for 15 h. The obtained precipitates were collected by centrifugation, washed three times with 2 mL of water, and dried under reduced pressure to give compounds 2a?f subsequently crystallized from benzene, Synthesis of (R)-Phenyl-3-oxo-4-[(phenoxycarbonyl)- amino]isoxazolidine-2-carboxylate (2a). 2a was obtained as a white crystalline solid in 85% yield, mp 159?160. 1 H NMR (DMSO-d 6 ): 8.58 (bs, 1H, D 2 O exchange), pp.3-155, 1956.

M. Esi, Synthesis of (R)-4-Methylphenyl-4-{[(4-methylphenoxy)- carbonyl]amino}-3-oxoisoxazolidine-2-carboxylate (2b). 2b was obtained as a white crystalline solid in 75% yield, pp.914-922

2. , J. =. 1h, and J. =. , 58 Hz); 5.02?4.95 (m, 1H), p.77

1. Mp, 1 H NMR (DMSO-d 6 ): 7.35 (s, 5H)06 (s, 2H); 4.87?4.80 (m, 1H), p.62

1. Dd, 2. , 1. , 1. , and J. =. , 77 Hz, J = 1.98 Hz)37 (m, 1H)30 Hz);7.24 (d, 2H); 5.15 (s, 2H), Hz, vol.7598787, issue.8, p.27979868

?. Associated, Supporting Information Tables S1-S10 and Figures S1-S17. This material is available free of charge via the Internet at http

?. , D. Perri, and G. , (2) Ehlers, S. Lazy, dynamic or minimally recrudescent? On the elusive nature and location of the mycobacterium responsible for latent tuberculosis Which agents should we use for the treatment of multidrug-resistant Mycobacterium tuberculosis?, Infection, vol.37, issue.13, 2009.

A. H. Ziazarifi, S. E. Hoffner, R. A. Amale, K. K. Ajbani, and C. Rodrigues, Emergence of new forms of totally drugresistant tuberculosis bacilli: super extensively drug-resistant tuberculosis or totally drug-resistant strains in iran Totally drug-resistant tuberculosis in India) Guy, E. S.; Mallampalli, A. Managing TB in the 21st century: existing and novel drug therapies Tuberculosis chemotherapy: recent developments and future perspectives, 420? 425. (5) Udwadia, pp.579-581, 2008.

D. Vita, D. Mellini, P. Fattorini, L. Ragno, R. Marshall et al., Activity of drugs against dormant Mycobacterium tuberculosis, J. Chemother, vol.23, issue.9, pp.175-178, 2011.

R. Rompei, M. Artico, G. C. Porretta, G. Poce, and D. Deidda, Antimycobacterial pyrroles: synthesis, anti- Mycobacterium tuberculosis activity and QSAR studies, Bioorg. Med. Chem, vol.8, issue.10, pp.1423-1432, 2000.

R. Pompei, P. Molicotti, F. Manetti, and M. Botta, Antimycobacterial agents. Novel diarylpyrrole derivatives of BM212 endowed with high activity toward Mycobacterium tuberculosis and low cytotoxicity, J

. Med, F. Chem-ballante, R. Ragno, and G. C. Porretta, 3-D QSAutogrid/R: an alternative procedure to build 3-D QSAR models. Methodologies and applications, 1674?1685. (12) Manetti, F.; Corelli, 2006.

M. Botta, D. Barnum, J. Greene, A. Smellie, P. Sprague et al., Identification of common functional configurations among molecules, Manetti, F. New derivatives of toluidine: Synthesis, antitubercular activity and pharmacophore hypothesis, pp.484-491, 1996.

M. Biava, G. C. Porretta, and D. Deidda, 1,5-Diphenylpyrrole Derivatives as Antimycobacterial Agents. Probing the Influence on Antimycobacterial Activity of Lipophilic Substituents at the Phenyl Rings, Journal of Medicinal Chemistry, vol.51, issue.12, pp.3644-3652, 2008.
DOI : 10.1021/jm701560p

F. Manetti, Antimycobacterial compounds New pyrrole derivatives of BM212, Bioorg. Med. Chem, vol.12, 2004.

A. Tafi and F. Manetti, Antimycobacterial compounds. Optimization of the BM 212 structure, the lead compound for a new pyrrole derivative class, 1221?30. (18) Biava, M.; Cesare Porretta, 2005.

F. Manetti, Importance of the thiomorpholine introduction in new pyrrole derivatives as antimycobacterial agents analogues of BM 212

D. Rossi, E. Manetti, F. Stammer, C. H. Kartha, C. C. Chaturvedi et al., -ethyl pyrrole derivatives as antimycobacterial agents: design, synthesis, and microbiological evaluation Cycloserine derivatives Electrogenerated acetonitrile anion induced selective N-alkylation of bifunctional compounds Ligand-based structural hypotheses for virtual screening AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility, 2564?2567. (22), pp.4734-4742, 1970.
URL : https://hal.archives-ouvertes.fr/dumas-00758263

M. Magnani, S. Supino, R. Meleddu, L. Chisu, and M. Botta, Synthesis, biological evaluation and SAR study of novel pyrazole analogues as inhibitors of Mycobacterium tuberculosis, Bioorg. Med. Chem, vol.16, pp.8587-91, 2008.