Conversion of a C20 2,3-oxidosqualene analog to tricyclic structures with a five-membered C-ring by lanosterol synthase. Further evidence for a C-ring expansion step in sterol biosynthesis

Tetrahedron Letters

Volumn 37, Issue 16, 1996, Pages 2709-2712

  Corey, E J ^a   Cheng, Hengmiao ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LANOSTEROL SYNTHASE; SQUALENE DERIVATIVE;

ARTICLE; BIOSYNTHESIS; CRYSTALLOGRAPHY; ENZYME ACTIVITY; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029962996     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00366-8     Document Type: Article

References (19)

1. For a recent review, see Abe, I.; Rohmer, M.; Prestwich, G. D. Chem. Rev. 1993, 93, 2189.
2. For a revision of the stereochemistry of the tetracyclization reaction, see (a) Corey, E. J.; Virgil, S. C. J. Am. Chem. Soc. 1991, 113, 4025.
3. (b) Corey, E. J.; Virgil, S. C.; Sarshar, S. J. Am. Chem. Soc. 1992, 114, 1524.
4. See (a) Kelly, R.; Miller, S. M.; Lai, M. H.; Kirsch, D. R. Gene, 1990, 87, 111 and Buntel, C. J.; Griffin, J. H. J. Am. Chem. Soc. 1992, 114, 9711 (Candida albicans).
5. See (a) Kelly, R.; Miller, S. M.; Lai, M. H.; Kirsch, D. R. Gene, 1990, 87, 111 and Buntel, C. J.; Griffin, J. H. J. Am. Chem. Soc. 1992, 114, 9711 (Candida albicans).
6. (b) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Proc. Natl. Acad. Sci. USA 1993, 90, 11628 (Arabidopsis thaliana).
7. (c) Corey, E. J.; Matsuda, S. P. T.; Bartel, B. Proc. Natl. Acad. Sci. USA 1994, 91, 2211 (Saccharomyces cerevisiae).
8. (d) Kasuno, M.; Shibuya, M.; Sankawa, U.; Ebizuka, Y. Biol. Pharm. Bull. Japan 1995, 18, 195 (Rattus norvegieus).
9. (e) Baker, C. H.; Matsuda, S. P. T.; Liu, D. R.; Corey, E. J. Biochem. Biophys. Res. Commun. 1995, 213, 154 (Homo sapiens).
10. Corey, E. J.; Virgil, S. C.; Cheng, H.; Baker, C. H.; Matsuda, S. P. T.; Singh, V.; Sarshar, S. J. Am. Chem. Soc. 1995, 117, 11819.
11. Synthesized by the reaction of Π - γ,γ-dimethylallyl barium with 2,3-oxidofarnesyl bromide; see Corey, E. J.; Noe; M. C.; Shieh, W.-C. Tetrahedron Lett. 1993, 34, 5995 and Corey, E. J.; Shieh, W.-C. Tetrahedron Lett. 1992, 33, 6435.
12. Synthesized by the reaction of Π - γ,γ-dimethylallyl barium with 2,3-oxidofarnesyl bromide; see Corey, E. J.; Noe; M. C.; Shieh, W.-C. Tetrahedron Lett. 1993, 34, 5995 and Corey, E. J.; Shieh, W.-C. Tetrahedron Lett. 1992, 33, 6435.
13. The solution also contained 20% glycerol, 0.2% triton X-100 and 3 mM dithiothreitol.
14. Substrate 6 was a weak competitive inhibitor of the cyclization of 2,3-oxidosqualene by lanosterol synthase. No time-dependent inactivation of the enzyme by 6 was observed.
15. 4).
16. The coordinates of the p-bromobenzoate of 7 can be obtained, on request, from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
17. 4); mp 146-147 °C (crystallized from EtOAc/pentane).
18. 4).
19. This work was supported by the National Institutes of Health. We are grateful to Mr. Mark C. Noe and Mr. Mihai Azimioara for the X-ray crystallographic analysis of the p-bromobenzoate of 7.