Stereoselective synthesis of PSI-352938: A β-D -2′-deoxy- 2′-α-fluoro-2′-β-C-methyl-3′,5′-cyclic phosphate nucleotide prodrug for the treatment of HCV

Journal of Organic Chemistry

Volumn 76, Issue 10, 2011, Pages 3782-3790

  Reddy, P Ganapati ^a   Chun, Byoung Kwon ^a   Zhang, Hai Ren ^a   Rachakonda, Suguna ^a   Ross, Bruce S ^a   Sofia, Michael J ^a  

^a PHARMASSET INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CBR; CHROMATOGRAPHIC PURIFICATION; CLINICAL DEVELOPMENT; CYCLIC PHOSPHATE NUCLEOTIDES; CYCLIC PHOSPHATES; DIASTEREOMERS; DIASTEREOSELECTIVE SYNTHESIS; EFFICIENT METHOD; FURTHER DEVELOPMENT; HEPATITIS C VIRUS; HIGH YIELD; IN-VITRO; IN-VIVO; ISOPROPYL ALCOHOLS; KEY FACTORS; POTASSIUM SALTS; PRODRUGS; RIBOFURANOSE; SCALABLE SYNTHESIS; SECOND GENERATION; STEREOSELECTIVE MANNER; STEREOSELECTIVE SYNTHESIS; SUPERIOR RESISTANCE; TRIPHOSPHATE;

CHROMATOGRAPHIC ANALYSIS; NUCLEOTIDES; STEREOCHEMISTRY; STEREOSELECTIVITY; SUGARS; VIRUSES;

SYNTHESIS (CHEMICAL);

2 PROPANOL; 6 (2 AMINO 6 ETHOXY 9H PURIN 9 YL) 7 FLUORO 2 ISOPROPOXY 7 METHYLTETRAHYDRO 4H FURO[3,2 D][1,3,2]DIOXAPHOSPHININE 2 OXIDE; ANTIVIRUS AGENT; NUCLEOTIDE DERIVATIVE; POTASSIUM SALT; PRODRUG; PSI 352938; PURINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; BROMINATION; CYCLIZATION; DIASTEREOISOMER; DRUG SYNTHESIS; HEPATITIS C; ISOMERIZATION; STEREOCHEMISTRY;

ANTIVIRAL AGENTS; CYCLIC P-OXIDES; CYCLIZATION; HEPACIVIRUS; NUCLEOSIDES; PRODRUGS; STEREOISOMERISM; SUBSTRATE SPECIFICITY;

EID: 79956069348     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo200060f     Document Type: Article

References (40)

1. Lavanchy, D. The global burden of hepatitis C Liver Int. 2009, 29 (S1) 74-81
2. Zeuzem, S.; Berg, T.; Moeller, B.; Hinrichsen, H.; Mauss, S.; Wedemeyer, H.; Sarrazin, C.; Hueppe, D.; Zehnter, E.; Manns, M. P. C. J. Viral. Hepat. 2009, 16, 75
3. Fried, M. W.; Shiffman, M. L.; Reddy, K. R.; Smith, C.; Marinos, G.; Goncales, F. L.; Haussinger, D.; Diango, M.; Carosi, G.; Dhumeaux, D.; Craxi, A.; Lin, A.; Hoffman, J.; Yu, J. N. Engl. J. Med. 2002, 347, 975
4. Burton, J. R.; Everson, G. T. Clin Liver Dis. 2009, 13, 453-465
5. Beaulieu, P. L. Expert Opin. Ther. Pat. 2009, 19, 145
6. Clark, J. L.; Hollecker, L.; Mason, J. C.; Stuyver, L. J.; Tharnish, P. M.; Lostia, S.; McBrayer, T. R.; Schinazi, R.; Watanabe, K. A.; Otto, M. J.; Furman, P. A.; Stec, W. J.; Patterson, S. E.; Pankiewicz, K. W. J. Med. Chem. 2005, 48, 5504
7. Stuyver, L. J.; McBrayer, T. R.; Tharnish, P. M.; Clark, J. L.; Hollecher, L.; Lostia, S.; Nachman; Grier, J.; Bennett, M. A.; Xie, M.-Y.; Schinazi, R. F.; Morrey, J. D.; Julander, J. L.; Furman, P. A.; Otto, M. J. Antiviral Chem. Chemother. 2006, 17, 79
8. Stuyver, L. J.; McBrayer, T. R.; Whitaker, T.; Tharnish, P. M.; Ramesh, M.; Lostia, S.; Cartee, L.; Shi, J.; Hobbs, A.; Schinazi, R. F.; Watanabe, K. A; Otto, M. J. Antimicrob. Agents Chemother. 2004, 48, 651
9. Sofia, M. J.; Bao, D.; Chang, W.; Du, J.; Nagarathnam, D.; Rachakonda, S.; Reddy, P. G.; Ross, B. S.; Wang, P.; Zhang, H.-R.; Bansal, S.; Espiritu, C.; Keilman, M.; Lam, A. M.; Micolochick Steuer, H. M.; Niu, C.; Otto, M. J.; Furman, P. A. J. Med. Chem. 2010, 53, 7202
10. Sofia, M. J.; Du, J.; Wang, P.; Nagarathnam, D. Intl. Pat. Appl. WO2008121634, 2008.
11. Wang, P.; Chun, B.-K.; Rachakonda, S.; Du, J.; Khan, N.; Shi, J.; Stec, W.; Cleary, D.; Ross, B. S.; Sofia, M. J. J. Org. Chem. 2009, 74, 6819
12. Reddy, R.; Rodriguez-Torres, M.; Gane, E.; Robson, R.; Lalezari, J.; Everson, G.; DeJesus, E.; McHutchinson, J.; Vargas, H. 58th Annual Meeting of the American Association of the Study of Liver Disease (AASLD), Boston, November 2007, Abstr. No. LB9. Lalezari, J.; Gane, E.; Rodriguez,-Torres, M.; DeJesus, E.; Nelson, D.; Everson, G.; Jacobson, I.; Reddy, R.; Hill, G. Z.; Beard, A.; Symonds, W. T.; Berrey, M. M.; McHutchison, J. G. 43rd Annual Meeting of the European Association for the Study of the Liver (EASL), Milan, April 2008.
13. Rodriguez-Torres, M.; Lalezari, J; Gane, E.; DeJesus, E.; Nelson, D.; Everson, G.; Jacobsen, I.; Reddy, R.; McHutchinson, J.; Beard, A.; Walker, S.; Symonds, B.; Berrey, M. 59th Annual Meeting of the American Association for the Study of Liver Disease, San Francisco, November 2008, Abstr. No. 1899.
14. Lawitz, E.; Lalezari, J.; Rodriguez-Torres, M.; Kowdley, K. V.; Nelson, D. R.; DeJesus, E.; McHutchison, J. G.; Compropst, M. T.; Mader, M.; Albanis, E.; Symonds, W. T.; Berry, M. M. 61st Annual Meeting of the American Association for the Study of Liver Disease, Boston, October 29-November 2, 2010, Abstr. No. 806.
15. Lawitz, E.; Lalezari, J.; Rodriguez-Torres, M.; Kowdley, K. V.; Nelson, D. R.; DeJesus, E.; McHutchison, J. G.; Compropst, M. T.; De La Rosa, A.; Symonds, W. T.; Berry, M. M. 61st Annual Meeting of the American Association for the Study of Liver Disease, Boston, October 29-November 2, 2010, Abstr. No. 1861.
16. Reddy, P. G.; Bao, D.; Chang, W.; Chun, B.-K.; Du, J.; Nagarathnam, D.; Rachakonda, S.; Ross, B. S.; Zhang, H.-R.; Bansal, S.; Espiritu, C. L.; Keilman, M.; Lam, A. M.; Niu, C.; Micolochick Steuer, H.; Furman, P. A.; Otto, M. J.; Sofia, M. J. Bioorg. Med. Chem. Lett. 2010, 20, 7376
17. Lam, A. M.; Espiritu, C. L.; Micolochick Steuer, H. M.; Murakami, E.; Niu, C.; Keilman, M.; Frick, D. N.; Heck, J. A.; Sofia, M. J.; Nagarathnam, D.; Chang, W.; Reddy, P. G.; Ross, B. S.; Chun, B.-K.; Wang, P.; Zhang, H.-R.; Rachakonda, S.; Bao, D.; Otto, M. J.; Furman, P. A. 60th Annual Meeting of the American Association for the Study of Liver Disease, Boston, October 30-November 3, 2009, Abstr. No. 1605.
18. Unpublished results (Pharmasset, Inc. press release, October 28, 2010.)
19. Clark, J. L.; Mason, J. C.; Hollecker, L.; Stuyer, L. J.; Tharnish, P. M.; McBrayer, T. R.; Otto, M. J.; Furman, P. A.; Schinazi, R. F.; Watanabe, K. A. Bioorg. Med. Chem. Lett. 2006, 16, 1712
20. Broeders, N. L. H. L.; Van Der Heiden, A. P.; Koole, L. H.; Kanters, J. A.; Schouten, A. Can. J. Chem. 1993, 71, 855
21. Broeders, N. L. H. L.; Koole, L. H.; Buck, H. M. J. Am. Chem. Soc. 1990, 112, 7475
22. Cruz-Gregorio, S.; Rodriguez-Palacios, V.; Hopfl, H.; Quintero, L.; Sartillo-Piscil, F. J. Org. Chem. 2009, 74, 197
23. Cruz-Gregorio, S.; Sanchez, M.; Clara-Sosa, A.; Bèrnes, S.; Quintero, L.; Sartillo-Piscil, F. J. Org. Chem. 2005, 70, 7107
24. Beres, J.; Sagi, G.; Bentrude, W. G.; Balzarini, J.; Clercq, E. D.; Otvos, L. J. Med. Chem. 1986, 29, 1243
25. Beres, J.; Sandor, P.; Kalman, A.; Koritsanszky, T.; Otvos, L. Tetrahedron 1984, 40, 2405
26. Gunic, E.; Girardet, J.-L.; Ramasamy, K.; Stoisavljevic-Petkov, V.; Chow, S.; Yeh, L.-T.; Hamatake, R. K.; Raney, A.; Hong, Z. Bioorg. Med. Chem. Lett. 2007, 17, 2452
27. Eldrup, A. B.; Prhavc, M.; Brooks, J.; Bhat, B.; Prakash, T. P.; Song, Q.; Bera, S.; Bhat, B.; Dande, P.; Cook, P. D.; Bennett, C. F.; Carroll, S. S.; Ball, R. G.; Bosserman, M.; Burlein, C.; Colwell, L. F.; Fay, J. F.; Flores, O. A.; Getty, K.; LaFemina, R. L.; Leone, J.; MacCoss, M.; McMasters, D. R.; Tomassini, J. E.; Langen, D. V.; Wolanski, B.; Olsen, D. B. J. Med. Chem. 2004, 47, 5284
28. Intramolecular 3′-O-C-6 bridged byproduct
29. Kazimierczuk, Z.; Cottam, H. B.; Revankar, G. R.; Robins, R. K. J. Am. Chem. Soc. 1984, 106, 6379
30. Okabe, M.; Sun, R. -C.; Zenchoff, G. B. J. Org. Chem. 1991, 56, 4392
31. Chun, B. K.; Olgen, S.; Hong, J. H.; Newton, M. G.; Chu, C. K. J. Org. Chem. 2000, 65, 685
32. Zhong, M.; Nowak, I.; Robins, M. J. J. Org. Chem. 2006, 71, 7773
33. Bauta, W.; Schulmeier, B. E.; Cantrell, W. R.; Lovelt, D.; Puente, J. Intl. Pat. Appl. WO 2003/011877.
34. Hoffer, M. Chem. Ber 1960, 93, 2777
35. Howell, H. G.; Brodfuehrer, P. R.; Brundidge, S. P.; Benigni, D. A.; Sapino, C., Jr. J. Org. Chem. 1988, 53, 85
36. Appel, R. Angew. Chem., Int. Ed. 1975, 14, 801
37. 3OD, 5.56:1). On the basis of these results, we believe that the anomeric effect favors the β-anomer in the neat liquid mixture of anomers while dynamic crystallization of β-lactol 14 drives the equilibrium to eventually give nearly exclusively the β-anomer solid.
38. Vargeese, C.; Carter, J.; Yegge, J.; Krivjansky, S.; Settle, A.; Kropp, E.; Peterson, K.; Pieken, W. Nucleic Acids Res. 1998, 26, 1046
39. Beaucage, S. L. In Current Protocols in Nucleic Acid Chemistry; Beaucage, S. L.; Bergstrom, D. E.; Glick, G. D.; Jones, R. A., Eds.; John Wiley & Sons: New York, NY, 2001; Chapter 3.
40. Although the role of NMI is not clear, we believe that NMI serves as a catalyst while triethylamine scavenges the HCl generated in the reaction.