Asymmetric synthesis of the potent HIV-protease inhibitor, nelfinavir

Journal of Organic Chemistry

Volumn 75, Issue 2, 2010, Pages 498-501

  Raghavan, Sadagopan ^a   Krishnaiah, V ^a   Sridhar, B ^a  

^a INDIAN INSTITUTE OF CHEMICAL TECHNOLOGY   (India)

Author keywords

[No Author keywords available]

Indexed keywords

ASYMMETRIC SYNTHESIS; CHEMICAL EQUATIONS; HIV-PROTEASE INHIBITORS; KEY FEATURE; STARTING MATERIALS; STEREO-SELECTIVE; STEREOSELECTIVE PREPARATION; SULFOXIDE GROUPS;

ALDEHYDES; ELECTRON TRANSITIONS; STEREOSELECTIVITY; VIRUSES;

SYNTHESIS (CHEMICAL);

ACROLEIN; IMINE; METHYLPHENYL SULFOXIDE; NELFINAVIR; SULFOXIDE; TERT BUTYL SULFINYLIMINE; UNCLASSIFIED DRUG;

ARTICLE; ASYMMETRIC SYNTHESIS; DRUG STRUCTURE; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS;

CATALYSIS; HIV PROTEASE INHIBITORS; MOLECULAR STRUCTURE; NELFINAVIR; STEREOISOMERISM;

EID: 75349099765     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo902048t     Document Type: Article

References (44)

1. (a) Appelt, K.; Bacquet, R. J.; Bartlett, C. A.; Booth, C. L. J.; Freer, S. T.; Fuhry, M. A. M.; Gehring, M. R.; Herrmann, S. M.; Howland, E. F.; Janson, C. A.; Jones, T. R.; Kan, C. C.; Kathardekar, V.; Lewis, K. K.; Marzoni, G. P.; Mathews, D. A.; Mohr, C.; Moomaw, E. W.; Morse, C. A.; Oatley, S. J.; Ogden, R. C.; Reddy, M. R.; Reich, S. H.; Schoettlin, W. S.; Smith, W. W.; Varney, M. D.; Villafranca, J. E.; Ward, R. W.; Webber, S.; Webber, S. E.; Welsh, K. M.; White, J. J. Med. Chem. 1991, 34, 1925.
2. (b) Shetty, B. V.; Kosa, M. B.; Khalil, D. A.; Webber, S. Antimicrob. Agents Chemother. 1996, 40, 110.
3. (c) Kaldor, S. W.; Kalish, V. J.; Davies, J. F.; Shetty, B. V.; Fritz, J. E.; Appelt, K.; Burgess, J. A.; Campanale, K. M.; Chirgadze, N. Y.; Clawson, D. K.; Dressman, B. A.; Hatch, S. D.; Khalil, D. A.; Kosa, M. B.; Lubbehusen, P. P.; Muesing, M. A.; Patick, A. K.; Reich, S. H.; Su, K. S.; Tatlock, J. H. J. Med. Chem. 1997, 40, 3979.
4. (a) Inaba, T.; Birchler, A. G.; Yamada, Y.; Sagawa, S.; Yokota, K.; Ando, K.; Uchida, I. J. Org. Chem. 1998, 63, 7582.
5. (b) The acid is available commercially from the Aldrich Chemical Company, Inc.
6. (a) Houpis, I. N.; Molina, A.; Reamer, R. A.; Lynch, J. E.; Volante, R. P.; Reider, P. J. Tetrahedron Lett. 1993, 34, 2593.
7. (b) Gohring, W.; Gokhale, S.; Hilpert, H.; Roessler, F.; Schlageter, M.; Vogt, P. Chimia 1996, 50, 532.
8. (c) Available from the Aldrich Chemical Company, Inc.
9. Rieger, D. L. J. Org. Chem. 1997, 62, 8546.
10. (a) Albizati, K. F.; Babu, S.; Birchler, A.; Busse, J. K.; Fugett, M.; Grubbs, A.; Haddach, A.; Pagan, M.; Potts, B.; Remarchuk, T.; Rieger, D.; Rodriguez, R.; Shanley, J.; Szendroi, R.; Tibbetts, T.; Whitten, K.; Borer, B. C. Tetrahedron Lett. 2001, 42, 6481.
11. (b) Kim, B. M.; Bae, S. J.; So, S. M.; Yoo, H. T.; Chang, S. K.; Lee, J. H.; Kang, J. Org. Lett. 2001, 3, 2349.
12. Ikunaka, M.; Matsumoto, J.; Fujima, Y.; Hirayama, Y. Org. Process Res. Dev. 2002, 6, 49.
13. (a) Inaba, T.; Yamada, Y.; Abe, H.; Sagawa, S.; Cho, H. J. Org. Chem. 2000, 65, 1623.
14. (b) Zook, S. E.; Busse, J. K.; Borer, B. C. Tetrahedron Lett. 2000, 41, 7017.
15. Ma, D.; Zou, B.; Zhu, W.; Xu, H. Tetrahedron Lett. 2002, 43, 8511.
16. For the oxidative functionalization of disubstituted alkenes, see: (a) Raghavan, S.; Rasheed, M. A.; Joseph, S. C.; Rajender, A. Chem Commun. 1999, 1845.
17. (b) Raghavan, S.; Ramakrishna Reddy, S.; Tony, K. A.; Naveen Kumar, Ch.; Varma, A. K.; Nangia, A. J. Org. Chem. 2002, 67, 5838.
18. (c) Raghavan, S.; Rajender, A.; Joseph, S. C.; Rasheed, M. A.; Ravi Kumar, K. Tetrahedron: Asymmetry 2004, 15, 365.
19. (d) For the oxidative functionalization of tri-substituted alkenes, see: Raghavan, S.; Sreekanth, T. Tetrahedron Lett. 2008, 49, 1169.
20. For the addition of α-sulfinyl carbanions to imines derived from nonenolizable aldehydes, see: (a) Tsuchihashi, G. I.; Iriuchijima, S.; Maniwa, K. Tetrahedron Lett. 1973, 14, 3389.
21. (b) Ronan, B.; Marchalin, S.; Samuel, O.; Kagan, H. B. Tetrahedron Lett. 1988, 29, 6101.
22. (c) Pyne, S. G.; Boche, G. J. Org. Chem. 1989, 54, 2663.
23. (d) Pyne, S. G.; Dikic, B. Chem. Commun. 1989, 826.
24. (e) Satoh, T.; Sato, T.; Oohara, T.; Yamakawa, K. J. Org. Chem. 1989, 54, 3973.
25. (f) Mahidol, C.; Reutrakul, V.; Prapansiri, V.; Panyachotipun, C. Chem. Lett. 1984, 969.
26. Pyne, S. G.; Dikic, B. J. Org. Chem. 1990, 55, 1932.
27. (a) Raghavan, S.; Rajender, A. Tetrahedron Lett. 2004, 45, 1919.
28. (b) Raghavan, S.; Rajender, A. Tetrahedron 2004, 60, 5059.
29. Ruano, J. L. G.; Alcudia, A.; Prado, M.; Barros, D.; Maestro, M. C.; Fernandes, I. J. Org. Chem. 2000, 65, 2856.
30. Optically pure methyl p-tolyl sulfoxide was used in initial experiments to standardize reaction conditions because it is more readily available in excellent optical purity by a number of oxidation protocols.
31. Drago, C.; Caggiano, L.; Jackson, R. F. W. Angew. Int., Ed. Eng. 2005, 44, 7221.
32. (a) Davis, F. A.; Zhang, Y.; Andemichael, Y.; Fang, T.; Fanelli, D. L.; Zhang, H. J. Org. Chem. 1999, 64, 1403.
33. (b) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 1278.
34. Davis, F. A.; Reddy, R. E.; Szewczyk, J. M.; Reddy, G. V.; Portonovo, P. S.; Zhang, H.; Fanelli, D.; Reddy, R. T.; Zhou, P.; Carroll, P. J. J. Org. Chem. 1997, 62, 2555.
35. Weix, D. J.; Ellman, J. A. Org. Lett. 2003, 5, 1317.
36. Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 12.
37. The structure of anti-19c was confirmed by NOE studies on the derived N,O-acetonide by reaction with 2,2-dimethoxypropane in the presence of cat CSA. The structure assigned to syn-19c was confirmed by oxidation to a sulfone which was identical to that obtained from anti-19c.
38. As pointed out in the text, though racemic methyl phenyl sulfoxide could be used, we chose the (S)-sulfoxide for the ease of interpretation of NMR spectra (single set of peaks). The sulfoxide was prepared following Jackson's protocol (ref 15) using the less expensive of the enantiomeric ligands.
39. See Supporting Information.
40. Westwell, A. D.; Thornton Pett, M.; Rayner, C. M. J. Chem. Soc., Perkin Trans. 1 1995, 847.
41. The initially formed epoxide probably undergoes an aza-Payne rearrangement followed by β-elimination of the resulting aziridine. Alternately, an azetidine could be formed which then suffers β-elimination under the basic conditions.
42. Drabowicz, J.; Oae, S. Synthesis 1977, 6, 404.
43. Miyata, O.; Ozawa, Y.; Ninomiya, I.; Naito, T. Tetrahedron 2000, 56, 6199.
44. Miller, S. C.; Scanlan, T. S. J. Am. Chem. Soc. 1997, 119, 2301.