Synthesis and enzymatic cyclization of (3S)11-fluoro-2,3-oxidosqualene

Tetrahedron Letters

Volumn 39, Issue 9, 1998, Pages 957-960

  Robustell, Brian ^a   Ikuro, Abe ^b   Prestwich, Glenn D ^b  

^a STONY BROOK UNIVERSITY   (United States)

^b UNIVERSITY OF UTAH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

11 FLUORO 2,3 OXIDOSQUALENE; BACTERIAL ENZYME; HOPANOID; LANOSTEROL; LANOSTEROL SYNTHASE; SQUALENE; SQUALENE DERIVATIVE; UNCLASSIFIED DRUG;

ALICYCLOBACILLUS ACIDOCALDARIUS; ARTICLE; CHEMICAL BOND; CYCLIZATION; NONHUMAN; SYNTHESIS; THERMOPHILIC BACTERIUM;

EID: 0032568049     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10669-4     Document Type: Article

References (34)

1. 1. For a review, see: Abe, I.; Rohmer, M.; Prestwich, G. D. Chem. Rev. 1993, 93, 2189.
2. 2. For vertebrate OSLCs, (a) Abe, I.; Bai, M.; Xiao, X.-y.; Prestwich, G. D. Biochem. Biophys. Res. Commun. 1992, 187, 32 (purification);
3. (b) Abe, I.; Prestwich, G. D. J. Biol. Chem. 1994, 269, 802 (active-site mapping);
4. (c) Abe, I.; Prestwich, G. D. Proc. Natl. Acad. Sci. USA 1995, 92, 9274 (cloning and expression).
5. 3. For A. acidocaldarius SHC: (a) Ochs, D.; Tappe, C. H.; Gärtner, P.; Kellner, R.; Poralla, K. Eur. J. Biochem. 1990, 194, 75 (purification);
6. (b) Ochs, D.; Kaletta, C.; Entian, K.-D.; Beck-Sickinger, A.; Poralla, K. J. Bacteriol. 1992, 174, 298 (cloning and expression),
7. (c) Feil, C.; Süssmuth, R.; Jung, G.; Poralla, K. Eur. J. Biochem. 1996, 242, 51 (site-directed mutagenesis);
8. (d) Wendt, K.-U.; Poralla, K.; Schulz, G. E. Science 1997, 277, 1811 (crystal structure).
9. (e) Abe I.; Dang, T.; Zheng, Y. F.; Madden, B. A.; Feil, C.; Poralla, K.; Prestwich, G. D. J. Am. Chem. Soc. 1997, in press (affinity labeling).
10. 4. (a) Poralla, K.; Hewelt, A.; Prestwich, G. D.; Abe, I.; Reipen, I.; Sprenger, G. Trends Biochem. Sci. 1994, 19, 157.;
11. (b) Poralla, K. Bioorg. Med. Chem. Lett. 1994, 4, 285;
12. (c) Dougherty, D. A. Science 1996, 271, 163.
13. 5. (a) Wang, L.; Sharpless, K. B. J. Am. Chem. Soc. 1992, 114, 7568.
14. (b) Xu, D.; Crispino, G. A.; Sharpless, K. B. J. Am. Chem. Soc. 1992, 114, 7570.
15. (c) Crispino, G. A.; Sharpless, K. B. Tetrahedron Lett. 1992, 33, 4273.
16. 6. (a) B. Robustell, M.Sc. Thesis, State University of New York at Stony Brook, Stony Brook, 1996;
17. 50FO (MH+) 445.3836; calcd. 445.3840.
18. 2a (3S)11-FOS (5.0 mg) was incubated with the enzyme in 100 mL of 100 mM Tris-HCl, pH 7.4, 0.1% Triton X-100 at 37 °C for 16 h. After extraction with EtOAc (300 mL × 2), no product was detected and (35)11-FOS (4.6 mg) was recovered unchanged. This was also confirmed by GC analysis.
19. 8. (a) 11-Fluorosqualene (11-FS) was first prepared as a pseudosubstrate for squalene epoxidase, but failed to be epoxidized enzymatically: S. Sen, Ph.D. Dissertation, State University of New York at Stony Brook, Stony Brook, 1989;
20. (b) An inseparable mixture of racemic 11-F- and 14-F-OS regioisomers was first chemically synthesized from 11-FS: Xiao, X.-y. Ph.D. Dissertation, State University of New York at Stony Brook, Stony Brook, 1991.
21. f = 0.4) to give 1.1 mg of compound 15. Control experiments were carried out at 4 °C or without enzyme preparation.
22. 49FO 444.3754; calcd. 444.3767. Complete spectral data may be requested from the authors.
23. 11. For example, see: (a) van Tamelen, E. E.; Coates, R. M. Bioorg. Chem, 1982, 11, 171;
24. (b) Fish, P. V.; Johnson, W. S. J. Org. Chem. 1994, 59, 2324.
25. 12. Under the same conditions, the recombinant A. acidocaldarius SHC converted (3S)2,3-oxidosqualene to 3β-hydroxyhop-22(29)-ene and hopan-3β,22-diol (I. Abe, unpublished data).
26. 14d
27. 14. Cell-free homogenates of hopanoid-producing microorganisms initiate cyclization reactions of oxidosqualene into pentacyclic triterpenes by oxirane ring opening. See: (a) Rohmer, M.; Anding, C.; Ourisson, G. Eur. J. Biochem. 1980, 112, 541;
28. (b) Rohmer, M.; Bouvier, P.; Ourisson, G. Eur. J. Biochem. 1980, 112, 557;
29. (c) Bouvier, P.; Berger, Y.; Rohmer, M.; Ourisson, G. Eur. J. Biochem. 1980, 112, 549;
30. (d) Abe, I.; Rohmer, M. J. Chem. Soc. Perkin Trans, 1 1994, 783.
31. 15. (a) Johnson, W. S.; Chenera, B.; Tham, F. S.; Kullnig, R. K. J. Am. Chem. Soc. 1993, 115, 493;
32. (b) Johnson, W. S.; Fletcher, V. R.; Chenera, B.; Bartlett, W. R.; Tham, F. S.; Kullnig, R. K. J. Am. Chem. Soc. 1993, 115, 497;
33. (c) Johnson, W. S.; Buchanan, R. A.; Bartlett, W. R.; Tham, F. S.; Kullnig, R. K. J. Am. Chem. Soc. 1993, 115, 504;
34. (d) Johnson, W. S.; Plummer, M. S.; Reddy, S. P.; Bartlett, W. R. J. Am. Chem. Soc. 1993, 115, 515.