Synthesis and conformational analysis of di-13C-labeled farnesyl diphosphate analogs

Tetrahedron Letters

Volumn 39, Issue 23, 1998, Pages 3991-3994

  Zahn, Todd J ^a   Ksebati, Mohamad B ^a   Gibbs, Richard A ^a  

^a WAYNE STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 13; FARNESYL DIPHOSPHONATE; ISOPRENOID; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL BOND; CONFORMATION; LIPID METABOLISM; SYNTHESIS;

EID: 0032482516     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00751-5     Document Type: Article

References (32)

1. 1. Gibbs, R. A. In Comprehensive Biological Catalysis; Sinnott, M. L., Ed.; Academic Press: London, 1998; Vol. 1, p 31-118.
2. 2. Broeker, J. L.; Hoffmann, R. W.; Houk, K. N. J. Am. Chem. Soc. 1991, 113, 5006-5017.
3. 3. Gung, B. W.; Zhu, Z.; Fouch, R. A. J. Am. Chem. Soc. 1995, 117, 1783-1788.
4. 4. Ernst, J.; Furhop, J.-H. Liebigs Ann. Chem. 1979, 1635-1642.
5. 5. Murgolo, N. J.; Patel, A.; Stivala, S. S.; Wong, T. K. Biochemistry 1989, 28, 253-260.
6. 6. Facke, T.; Berger, S. J. Am. Chem. Soc. 1995, 117, 9547-9550.
7. 7. Note that Biller and coworkers have reported that FPP analogs that mimic the eclipsed conformation C are very potent inhibitors of squalene synthase, which suggests that FPP assumes this conformation in the active site of this enzyme: Biller, S. A.; Abt, J. W.; Pudzianowski, A. T.; Rich, L. C.; Slusarchyk, D. A.; Ciosek, C. P., Jr. Bioorg. Med. Chem. Lett. 1993, 3, 595-600.
8. 8. Marshall, J. L. Carbon-Carbon and Carbon-Proton NMR Couplings: Applications to Organic Stereochemistry and Conformational Analysis; Verlag Chemie International: Deerfield Beach, FL, 1983.
9. 9. Krivdin, L. B.; Della, E. W. Prog. Nucl. Magn. Res. Spectrosc. 1991, 23, 301-610.
10. 10. Menger, F. M.; Carnahan, D. W. J. Am. Chem. Soc. 1986, 108, 1297-1298.
11. 11. Gibbs, R. A.; Krishnan, U.; Dolence, J. M.; Poulter, C. D. J. Org. Chem. 1995, 60, 7821-7829.
12. 12. Mu, Y. Q.; Gibbs, R. A.; Eubanks, L. M.; Poulter, C. D. J. Org. Chem. 1996, 61, 8010-8015.
13. 13. Leonard, D. M. J. Med. Chem. 1997, 40, 2971-2990.
14. 13C-geranylgeraniol: Eis, K.; Schmalz, H.-G. Synthesis 1997, 202-206. See also: Christensen, D. J.; Poulter, C. D. Bioorg. Med. Chem. 1994, 2, 631-638.
15. 13C-geranylgeraniol: Eis, K.; Schmalz, H.-G. Synthesis 1997, 202-206. See also: Christensen, D. J.; Poulter, C. D. Bioorg. Med. Chem. 1994, 2, 631-638.
16. 15. Cane, D. E. Chem. Rev. 1990, 90, 1089-1103.
17. 16. Gibbs, R. A.; Krishnan, U. Tetrahedron Lett. 1994, 35, 2509-2512.
18. 17. Mu, Y. Q.; Gibbs, R. A. Tetrahedron Lett. 1995, 36, 5669-5672.
19. 18. Urano, S.; Otani, I.; Matsuo, M. Heterocycles 1985, 23, 2793-2796.
20. 19. Sum, F. W.; Weiler, L. Can. J. Chem. 1979, 57, 1431-1441.
21. 20. Groesbeek, M.; Lugtenburg, J. Photochem. and Photobiol. 1992, 56, 903-908.
22. 21. Davisson, V. J.; Woodside, A. B.; Neal, T. R.; Stremler, K. E.; Muehlbacher, M.; Poulter, C. D. J. Org. Chem. 1986, 51, 4768-4779.
23. 26O - 224.2052; found for 1: 224.2048; found for 3: 224.2050.
24. 23. The labeled acetoacetate is commercially available (Cambridge Isotope Laboratories), or it can be synthesized using the following method: Winkel, C.; Buitenhuis, E. G.; Lugtenburg, J. Recl. Trav. Chim. Pays-Bas 1989, 108, 51-56.
25. 24. Dawe, A. L.; Becker, J. M.; Jiang, Y.; Naider, F.; Eummer, J. T.; Mu, Y. Q.; Gibbs, R. A. Biochemistry 1997, 36, 12036-12044.
26. 25. Cane, D. E. Acc. Chem. Res. 1985, 18, 220-226.
27. 26. Menger, F. M.; D'Angelo, L. L. J. Am. Chem. Soc. 1988, 110, 8241-8242.
28. 27. The coupling constant observed for 4 could be due to its micellar form, but note that Menger and coworkers have found that the gauche conformational preference can be increased, rather than decreased, in micelles: Menger, F. M.; Dulany, M. A.; Carnahan, D. W.; Lee, L. H. J. Am. Chem. Soc. 1987, 109, 6899-6900.
29. 28. Starks, C. M.; Back, K.; Chappell, J.; Noel, J. P. Science 1997, 277, 1815-1820.
30. 29. Lesburg, C. A.; Zhai, G.; Cane, D. E.; Christianson, D. W. Science 1997, 277, 1820-1824.
31. 30. Park, H. W.; Boduluri, S. R.; Moomaw, J. F.; Casey, P. J.; Beese, L. S. Science 1997, 275, 1800-1804.
32. 31. Smith, S. O.; Aschheim, K.; Groesbeek, M. Quart. Rev. of Biophys. 1996, 29, 395-449.