Antibody catalyzed terpenoid cyclization

Journal of the American Chemical Society

Volumn 118, Issue 46, 1996, Pages 11654-11655

  Hasserodt, Jens ^a   Janda, Kim D ^a   Lerner, Richard A ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; TERPENE;

ARTICLE; CATALYSIS; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0029909229     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja954316w     Document Type: Article

References (24)

1. It should be emphasized that monoterpene biosynthesis generally follows a different cyclization mechanism than the following, generating an allylic cation from geranyl pyrophosphate (9) subsequently rearranging to the linalyl cation which adds to the second double bond in a Markovnikoff fashion (Scheme 3).
2. For an entry to monoterpene cyclases isolated from plants, see: (a) Rajaonarivony, J.; Gershenzon, J.; Croteau, R. Arch. Biochem. Biophys. 1992, 296, 49-57.
3. For a review on terpene cyclase isolation, see: (b) Croteau, R.; Cane, D. E. In Methods in Enzymology; Law, J. H., Rilling, H. C., Eds.; Academic Press: New York, 1985; pp 383-405.
4. (a) Ruzicka, L.; Eschenmoser, A.; Heusser, H. Experientia 1953, 9, 357-367.
5. (b) Stork, G.; Burgstahler, A. W. J. Am. Chem. Soc. 1955, 77, 5068-5077.
6. (c) Eschenmoser, A.; Ruzicka, L.; Jeger, O.; Arigoni, D. Helv. Chim. Acta 1955, 38, 1890-1905.
7. (a) Brown, D. J.; Evans, R. F. J. Chem. Soc. 1962, 527-533.
8. (b) Ibid. 1962, 4039-4045.
9. Julia, M.; Descoins, C.; Baillarge, M.; Jacquet, B.; Uguen, D.; Groeger, F. A. Tetrahedron 1975, 31, 1737-1744.
10. (a) Li, T.; Janda, K. D.; Ashley, J. A.; Lerner, R. A. Science 1994, 264, 1289-1293.
11. (b) Li, T.; Hilton, S.; Janda, K. D. J. Am. Chem. Soc. 1995, 117, 3308-3309.
12. (c) Johnson, W. S.; Bailey, D. M.; Owyang, R.; Bell, R. A.; Jaques, B.; Crandall, J. K. J. Am. Chem. Soc. 1964, 86, 1959-1966.
13. Köhler, G.; Milstein, C. Nature 1975, 256, 495-497.
14. Hexane/chloroform/phosphate buffer (83:2:15%), 50 mM, pH 7.1; shaken in a sealed Teflon tube for defined time units.
15. See also: Ashley, J. A.; Janda, K. D. J. Org. Chem. 1992, 57, 6691-6693.
16. Carbocycles 2 and 3 were formed with an ee of 24 and 37%, respectively. Without crystallographic data for IgG 17G8, it is difficult to speculate on the origins of this result. However, hapten 7 displays a planar geometry in the region where the stereocenter is being generated, and thus, we would not expect appreciable optical induction to be enforced in this region of the antibody's combining site.
17. It should be noted that natural terpene cyclase reactions also display multiple product formation (see: ref 2a, pp 52 and 56).
18. The complete absence of any linear product like 8, arising from simple hydrolysis of substrate 1 may be attributed to our biphasic assay conditions as well as the strength of the anchimeric effect of the double bond found in 1 (see: ref 6c).
19. M values of 0.5-3.0 μM for their respective pyrophosphate substrates (ref 2a, p 53).
20. Since a fully functional IgG molecule was used, this corresponds to a 1:1 ratio of inhibitor to binding site. The same finding was also observed with antibodies 1F8 and 12E8.
21. Williams, J. W.; Morrison, J. F. In Methods in Enzymology; Purich, D. L., Ed.; Academic Press: New York, 1979; pp 437-467.
22. A 24 h assay consisting of 16 μM IgG 17G8 and 600 μM 1 resulted in 95% solvolysis of 1. No activity loss was observed after replacing the hexane phase and recharging the system with fresh substrate.
23. Compounds 2, 3, and 6 are analogous in their double-bond regiochemistry to α-, γ- (the fragrance principle of violets), and β-irones, respectively. See: Jaenicke, L.; Marner, F.-J. Pure Appl. Chem. 1990, 62, 1365-1368 and research on biosynthesis cyclization mechanisms therein.
24. See this article and references therein: Corey, E. J.; Virgil, S. C.; Cheng, H.; Baker, C. H.; Matsuda, S. P.; Singh, V.; Sarshar, S. J. Am. Chem. Soc. 1995, 117, 11819-11820.