C
A. Quotadamo et al.
Letter
Synlett
Acknowledgment
(23) Kristiansen, A.; Grgic, M.; Altermark, B.; Leiros, I. J. Antimicrob.
Chemother. 2015, 70, 766.
(24) Jones, R. N.; Wilson, H. W.; Novick, W. J.; Barry, A. L.;
Thornsberry, C. J. Clin. Microbiol. 1982, 15, 954.
This work was supported by the OPTObacteria project within the 7FP
(Grant agreement no: 286998; www.optobacteria.eu).
(25) 5-Mercapto-2-nitrobenzoic Acid (TNB, 1)
In a 50 mL one-neck round-bottom flask, 5,5′-dithiobis(2-nitro-
benzoic acid) (420 mg, 1.06 mmol, 1 equiv) was slurried in 80%
EtOH (v/v, 5 mL) cooled to 0 °C with an ice bath. NaBH4 (320 mg,
8.46 mmol, 8 equiv) was dissolved in distilled water (2 mL) and
slowly added dropwise through an addition funnel (CAUTION!
Vigorous effervescence develops!). The resulting dark red
mixture was stirred at r.t. until gas evolution subsided. After
dilution with EtOH (5 mL) and distilled water (5 mL), the
mixture was acidified with 2 N HCl, extracted with CH2Cl2 (3 ×
20 mL), and the pooled organic layers were washed with dis-
tilled water (3 × 50 mL) and brine (3 × 50 mL). The yellow
organic solution was dried over Na2SO4, filtered, and concen-
trated to dryness to afford the desired thiol as a bright orange
solid (410 mg, 97% yield); mp 143–145 °C. 1H NMR (400 MHz,
CDCl3): δ = 3.84 (1 H, s, SH), 5.77 (1 H, br, COOH), 7.48 (1 H, dd, J
= 8.5, 2.1 Hz, H-4), 7.63 (1 H, d, J = 2.1 Hz, H-6), 7.86 (1 H, d, J =
8.5 Hz, H-3). 13C NMR (100 MHz, CDCl3): δ = 125.2 (C-3), 126.6
(C-1), 128.8 (C-6), 128.9 (C-4), 141.6 (C-5), 146.5 (C-2), 165.3
(COOH). MS: m/z = 200.1 [M + H]+; 198.0 [M – H]–. Anal. Calcd
for C7H5NO4S: C, 42.21; H, 2.53; N, 7.03. Found: C, 42.19; H,
2.55; N, 7.07.
Supporting Information
Supporting information for this article is available online at
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References and Notes
(1) Livermore, D. M.; Brown, D. F. J. Antimicrob. Chemother. 2001,
48, 59; Suppl. 1.
(2) van Berkel, S. S.; Brem, J.; Rydzik, A. M.; Salimraj, R.; Cain, R.;
Verma, A.; Owens, R. J.; Fishwick, C. W. G.; Spencer, J.;
Schofield, C. J. J. Med. Chem. 2013, 56, 6945.
(3) Bidya, S.; Suman, R. Open J. Clin. Diagn. 2014, 4, 47.
(4) Montgomery, K.; Raymundo, L.; Drew, W. L. J. Clin. Microbiol.
1979, 9, 205.
(5) Papanicolaou, G. A.; Medeiros, A. A. Antimicrob. Agents Chemo-
ther. 1990, 34, 2184.
(6) Kobayashi, S.; Arai, S.; Hayashi, S.; Sakaguchi, T. Antimicrob.
Agents Chemother. 1988, 32, 1040.
(7) (a) O'Callaghan, C. H.; Morris, A.; Kirby, S. M.; Shingler, A. H.
(26) (6R,7R)-7-Amino-3-{[(3-carboxy-4-nitrophenyl)thio]-methyl}-
8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid
(2)
Antimicrob.
Agents
Chemother.
1972,
1,
283.
-CAS-41906-86-9---Calbiochem,EMD_BIO-484400?bd=1.
(8) Pitkälä, A.; Salmikivi, L.; Bredbacka, P.; Myllyniemi, A.-L.;
Koskinen, M. T. J. Clin. Microbiol. 2007, 45, 2031.
(9) Marshall, S. A.; Sutton, L. D.; Jones, R. N. Diagn. Microbiol. Infect.
Dis. 1995, 22, 353.
(10) Uri, J. V. Acta Microbiol. Hung. 1985, 32, 133.
(11) (a) Bebrone, C.; Moali, C.; Mahy, F.; Rival, S.; Docquier, J. D.;
Rossolini, G. M.; Fastrez, J.; Pratt, R. F.; Frere, J. M.; Galleni, M.
7-Aminocephalosporanic acid (7-ACA, 0.547 g, 2.01 mmol, 1
equiv) and 5-mercapto-2-nitrobenzoic acid (1, 0.400 g, 2.01
mmol, 1 equiv) were successively added to a stirred solution of
BF3 (1 M solution in THF, 6.03 mL, 6.03 mmol, 3 equiv) in 40 mL
anhydrous MeCN, and the resulting solution was stirred at r.t.
for 2 h. After cooling in an ice-bath, the mixture was diluted
with water (50 mL) and adjusted to pH 4.0 by addition of 28%
NH4OH. The resulting ochre-yellow precipitate was collected by
filtration and washed with water and acetone to afford the title
compound as a light ochre powder (0.768 g, 93%); mp 184 °C
Antimicrob.
Agents
Chemother.
2001,
45,
1868.
(b) http://www.merckmillipore.com/FR/fr/product/CENTA%E2%
84%A2-%CE%B2-Lactamase-Substrate---CAS-9073-60-3---Cal-
biochem,EMD_BIO-219475.
25
1
(dec.); [α]D = –26.4 (1.07% w/v in DMSO). H NMR (400 MHz,
DMSO-d6): δ = 3.49 (1 H, d, J = 17.8 Hz, H-4), 3.69 (1 H, d, J = 17.8
Hz, H-4), 4.16 (1 H, d, J = 12.8 Hz, CH2–C-3), 4.29 (1 H, d, J = 12.8
Hz, CH2–C-3), 4.77 (1 H, d, J = 5.0 Hz, H-7), 4.98 (1 H, d, J = 5.0
Hz, H-6), 7.62 (1 H, dd, J = 8.6, 1.9 Hz, H-6′), 7.66 (1 H, d, J = 1.9
Hz, H-2′), 7.93 (1 H, d, J = 8.6 Hz, H-5′). 13C NMR (100 MHz,
DMSO-d6): δ = 27.2 (C-4), 35.2 (CH2–C-3), 59.4 (C-6), 63.5 (C-7),
124.5 (C-3)*, 125.0 (C-5´), 126.8 (C-2)*, 128.0 (C-2′), 130.2 (C-
6′), 144.7 (C-1′), 145.1 (C-4′), 163.8 (C-2–COOH), 166.4 (C-3′–
COOH), 169.4 (C-8) [* assignments may be interchangeable].
MS: m/z = 412.1 [M + H]+; 410.0 [M – H]–. Anal. Calcd for
(12) Morin, S.; Clouthier, C. M.; Gobeil, S.; Pelletier, J. N.; Gagne, S. M.
Biomol. NMR Assignments 2010, 4, 127.
(13) Padiolleau-Lefevre, S.; Debat, H.; Thomas, D.; Friboulet, A.;
Avalle, B. Biocatal. Biotransform. 2003, 21, 79.
(14) Hugonnet, J.-E.; Blanchard, J. S. Biochemistry 2007, 46, 11998.
(15) Mandal, S.; Maharjan, M.; Ganguly, S.; Chatterjee, M.; Singh, S.;
Buckner, F. S.; Madhubala, R. Indian J. Exp. Biol. 2009, 47, 475.
(16) Yang-Woytowitz, M.; Yu, C.; Wiles, T. WO 2009051838 A1, 2009.
(17) Bebrone, C.; Anne, C.; De Vriendt, K.; Devreese, B.; Rossolini, G.
M.; Van Beeumen, J.; Frere, J. M.; Galleni, M. J. Biol. Chem. 2005,
280, 28195.
(18) Page, M. G. P. Biochim. Biophys. Acta 1994, 1205, 199.
(19) Vella, P.; Hussein, W. M.; Leung, E. W. W.; Clayton, D.; Ollis, D.
L.; Mitić, N.; Schenk, G.; McGeary, R. P. Bioorg. Med. Chem. Lett.
2011, 21, 3282.
(20) Perumal, S. K.; Pratt, R. F. J. Org. Chem. 2006, 71, 4778.
(21) Makena, A.; van Berkel, S. S.; Lejeune, C.; Owens, R. J.; Verma, A.;
Salimraj, R.; Spencer, J.; Brem, J.; Schofield, C. J. ChemMedChem
2013, 8, 1923.
(22) Hailu, T. T.; Foit, L.; Bardwell, J. C. A. Anal. Biochem. 2013, 434,
181.
C
15H13N3O7S2: C, 43.79; H, 3.18; N, 10.21. Found: C, 43.76; H,
3.17; N, 10.24.
(27) Saikawa, I.; Takano, S.; Momonoi, K.; Takakura, I.; Tanaka, K.;
Kutani, C. Chem. Pharm. Bull. 1985, 33, 5534.
(28) (6R,7R)-3-{[(3-Carboxy-4-nitrophenyl)thio]methyl}-8-oxo-
7-]2-(thiophen-2-yl)acetamido]-5-thia-1-azabicy-
clo[4.2.0]oct-2-ene-2-carboxylic acid (CENTA, 3)
(a) Method c
A solution of potassium trimethylsilanolate (0.218 g, 1.7 mmol,
2 equiv) and 2-thienylacetyl chloride (0.136 g, 0.850 mmol, 1
equiv) in anhydrous MeCN (10 mL) was added simultaneously
to a suspension of 2 (0.35 g, 0.850 mmol, 1 equiv) in anhydrous
CH2Cl2 (30 mL) at 0 °C over 0.5 h. The resulting mixture was
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D