A practical synthesis of an anti-methicillin resistant Staphylococcus aureus cephalosporin BMS-247243

Organic Process Research and Development

Volumn 4, Issue 6, 2000, Pages 488-497

  Singh, Janak ^a   Kim, Oak K ^g   Kissick, Thomas P ^a   Natalie, Kenneth J ^b   Zhang, Bo ^a   Crispino, Gerard A ^d   Springer, Dane M ^g   Wichtowski, John A ^g   Zhang, Yunhui ^g   Goodrich, Jason ^g   Ueda, Yasutsugu ^g   Luh, Bing Y ^g   Burke, Brian D ^a   Brown, Matthew ^b   Dutka, Anthony P ^b   Zheng, Bin ^b   Hsieh, Dau Ming ^b   Humora, Michael J ^b   North, Jeffrey T ^a   Pullockaran, Anne J ^a   Livshits, Juliya ^a   Swaminathan, Shankar ^d   Gao, Zhinong ^d   Schierling, Peter ^c   Ermann, Peter ^c   Perrone, Robert K ^e   Lai, Mei C ^e   Gougoutas, Jack Z ^f   DiMarco, John D ^f   Bronson, Joanne J ^g   Heikes, James E ^b   Grosso, John A ^d   Kronenthal, David R ^b   Denzel, Theodor W ^c   Mueller, Richard H ^a   more..

^a BRISTOL MYERS SQUIBB PHARMACEUTICAL RESEARCH INSTITUTE   (United States)

^b Bristol Myers Sauibb P   (United States)

^c Process Technology ^*

^d Bristol Meyers Squibb   (United States)

^e Pharmaceutical Research Institute   (United States)

^f Solid State Chemistry   (United States)

^g Anti infective Chemistry   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0034311325     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op0002850     Document Type: Article

References (37)

1. D'Andrea, S. V.; Bonner, D.; Bronson, J. J.; Clark, J.; Denbleyker, K.; Fung-Tomc, J.; Hoeft, S. E.; Hudyma, T. W.; Matiskella, J. D.; Miller, R. F.; Misco, P. F.; Pucci, M.; Sterzycki, R.; Tsai, Y.; Ueda, Y.; Wichtowski, J. A.; Singh, J.; Kissick, T. P.; North, J. T.; Pullockaran, A.; Humora, M.; Boyhan, B.; Vu, T.; Fritz, A.; Heikes, J.; Fox, R.; Godfrey, J. D.; Perrone, R.; Kaplan, M.; Kronenthal, D.; Mueller, R. H. Tetrahedron 2000, 56, 5687 and references therein.
2. Kim, O. K.; Hudyma, T. W.; Matiskella, J. D.; Ueda, Y.; Bronson, J. J.; Mansuri, M. M. Bioorg. Med. Chem. Lett. 1997, 7, 2753 and references therein.
3. (a) Haddad, J.; Vakulenko, S.; Mobashery, S. J. Am. Chem. Soc. 1999, 121, 11922.
4. (b) Lee, W.; Li, Z.-H.; Vakulenko, S.; Mobashery, S. J. Med. Chem. 2000, 43, 128.
5. Wood, M. J. J. Chemother. 1999, 11, 446.
6. Williams, D. H.; Bardsley, B. Angew. Chem., Int. Ed. 1999, 38, 1172.
7. Pechere, J. C. J. Antimicrob. Chemother. 1999, 44 (Topic A), 11.
8. Springer, D. M.; Luh, B. Y.; D'Andrea, S. V.; Hudyma, T. W.; Kim, O. K. EP 966472 A1, December, 29, 1999.
9. Brandstrom, A.; Lamm, B. Acta Chem. Scand. B, 1974, 28, 590.
10. King, C.; Ozog, F. J.; Moffat, J. J. Am. Chem. Soc. 1951, 73, 300.
11. Cava, M. P.; Levinson, M. I. Tetrahedron, 1985, 41, 5061.
12. Stillings, M. R.; Welbourn, A. P.; Walter, D. S. J. Med. Chem. 1986, 29, 2280.
13. Carreno, M. C.; Ruano, J. L. G.; Sanz, G.; Toledo, M. A.; Urbano, A. Tetrahedron Lett. 1996, 37, 4081.
14. Mattern, D. L.; Chen, X. J. Org. Chem. 1991, 56, 3.
15. Cabri, W.; Candiani, I. Acc. Chem. Res. 1995, 28, 2.
16. Plevyak, J. E.; Dickerson, J. E.; Heck, R. F. J. Org. Chem. 1979
17. Bumagin, A.; More, P. G.; Beletskaya, I. P. J. Organomet. Chem. 1989, 371, 397
18. Cecchetti, V.; Fravolini, A.; Fringuelli, R.; Mascellani, G.; Pagella, P.; Palmioli, M.; Segre, G.; Terni, P. J. Med. Chem. 1987, 30, 465.
19. Kanazawa, H.; Senga, K.; Tamura, Z. Chem. Pharm. Bull. 1985, 33, 618.
20. ACLH·HCl was purchased from Otsuka Chemical Company, Japan.
21. HPLC method: Wavelength 260 nm; solvent A: 0.2% aqueous phosphoric acid; solvent B: 90% acetonitrile/10% water; flow rate 1.5 ml/min. (a) Column: YMC S3 ODS-A 6.0 × 150 mm; start B = 0%, final B = 100%, gradient time = 20 min, hold time 10 min. (b) Column: YMC S3 Ph 6.0 × 150 mm; start B = 30%, final B = 55%, gradient time = 60 min. (c) same as method (a) but with gradient time = 30 min.
22. Woodward, R. B.; Heusler. K.; Gosteli, J.; Naegeli, P.; Oppolzer, W.; Ramage, R.; Ranganathan, S.; Vorbruggen, H. J. Am. Chem. Soc. 1966, 88, 852.
23. Morin, R. B.; Jackson, B. G.; Mueller, R. A.; Lavagnino, E. R.; Scanlon, W. B.; Andrews, S. L. J. Am. Chem. Soc. 1969, 91, 1401.
24. Bentley, P. H.; Brooks, G.; Zomaya, I. Tetrahedron Lett. 1976, 41, 3739.
25. Kaiser, G. V.; Cooper, R. D. G.; Koehler, R. E.; Murphy, C. F.; Webber, J. A.; Wright, I. G.; Van Heyningen, E. M. J. Org. Chem. 1970, 35, 2430.
26. Mobashrey, S.; Johnston, M. J. Org. Chem. 1986, 51, 4723.
27. Diacid 19 could not be analyzed by HPLC due to its instability. It was unstable also in DMSO, and therefore NMR spectra were taken in deuterated THF or DMF.
28. Possible paths for the degradation of cephem diacid 19 to the diacid 20 are outlined below. (formula presented) 20: degradation product
29. The structure of the diacid 20 was confirmed by the following synthesis. Acylation of tert-butylgiycine with monoacid ester 12b formed diester (i) which on double deprotection gave diacid 20. (formula presented)
30. Halpern, B.; Nitecki, D. E. Tetrahedron Lett. 1967, 8, 3031.
31. Diphenylmethyl ester hydrolyzed selectively on heating diester 21 in water at 80 °C. After 10 min the ratio of the mono-tert-butyl ester 21 to the diester 25 was 2.6:1.
32. A minor amount (<0.1%) of the byproduct disulfide (i) was isolated by column chromatography of one of the partially deprotected batches to prepare a reference sample of monoester 25. The structure is based on NMR spectra and MS/MS analysis (Dr. Haiying Zhang, AR & D, Princeton).
33. Pearson, D. A.; Blanchette, M.; Baker, M. L.; Guindon, C. A. Tetrahedron Lett. 1989, 30, 2739.
34. (a) Use of the Advancec Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under Contract No. W-31-109-Kng-38. (b) Crystallographic data (excluding structure factors) for the structure in this paper have been deposited with the Cambridge Cristallographic Data Centre. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, CambridgeCB21EZ,UK(fax: +441223336033 ore-mail: deposit@ccdc.cam.ac.uk). (c) Data were collected at beamline 17-ID in the facilities of the Industrial Macromolecular Crystallography Association Collaborative Access Team (IMCA-CAT) at the Advanced Photon Source. These facilities are supported by the companies of the Industrial Macromolecular Crystallography
35. R 14 9.2 min, 12a 6.2 min, 12b 3.7 min, DMF 2.0 min.
36. This reaction required 2 days at room temperature.
37. f 4 0.74, 5 0.14. (c) EtOAc:heptane = 1:4, visualized by UV.