A promiscuous proton in taxadiene biosynthesis?

Organic Letters

Volumn 9, Issue 6, 2007, Pages 1069-1071

  Gutta, Pradeep ^a   Tantillo, Dean J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKENE; DITERPENE; PROTON; TAXA 4(5),11(12)DIENE; TAXA-4(5),11(12)DIENE; UNCLASSIFIED DRUG;

ALGORITHM; ARTICLE; CHEMICAL STRUCTURE; METABOLISM; QUANTUM THEORY; THERMODYNAMICS;

ALGORITHMS; ALKENES; DITERPENES; MOLECULAR STRUCTURE; PROTONS; QUANTUM THEORY; THERMODYNAMICS;

EID: 33947673565     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol070007m     Document Type: Article

References (32)

1. (a) Koepp, A. E.; Hezari, M.; Zajicek, J.; Vogel, B. S.; LaFever, R. E.; Lewis, N. G.; Croteau, R. J. Biol. Chem. 1995, 270, 8686-8690.
2. (b) Hezari, M.; Lewis, N. G.; Croteau, R. Arch. Biochem. Biophys. 1995, 322, 437-444.
3. (c) Jin, Y. H.; Williams, D. C.; Croteau, R.; Coates, R. M. J. Am. Chem. Soc. 2005, 127, 7834-7842.
4. (d) Jin, Q. W.; Williams, D. C.; Hezari, M.; Croteau. R.; Coates, R. M. J. Org. Chem. 2005, 70, 4667-4675.
5. Hanson, J. R. Nat. Prod. Rep. 2006, 875-885 and references therein.
6. All calculations were performed with Gaussian03 (Frisch, M. J.; et al., Gaussian, Inc.: Pittsburgh, PA, 2003). Geometries were optimized using the B3LYP/6-31+G(d,p) method; see the Supporting Information for details, complete references, and comparisons with mPW1PW91 calculations. The range for electrostatic potential surfaces (Scheme 2) is +0.07 (red) to +0.13 au (blue); the front of each surface has been clipped to expose the interior.
7. (a) Lin, X.; Hezari, M.; Koepp, A. E.; Floss, H. G.; Croteau, R. Biochemistry 1996, 35, 2968-2977.
8. (b) Williams, C. D.; Carroll, B. J.; Jin, Q.; Rithner, C. D.; Lenger, S. R.; Floss, G. H.; Coates, R. M.; Williams, R. M.; Croteau, R. Chem. Biol. 2000, 7, 969-977.
9. (c) Chow, S. Y.; Williams, H. J.; Huang, Q.; Nanda, S.; Scott, A. I. J. Org. Chem. 2005, 70, 9997-10003.
10. (a) Similar proposals have been advanced for other terpene synthases. See, for example: Schenk, D. J.; Starks, C. M.; Rising Manna, K.; Chappell, J.; Noel, J. P.; Coates, R. M. Arch. Biochem. Biophys. 2006, 448, 31-44.
11. (b) Labeling experiments (see ref 1c) have shown that the stereochemical course of the taxadiene-forming rearrangement is indeed consistent with direct conversion of GGPP to 3 without the intermediacy of 1 or 2.
12. Similar intramolecular proton transfers have been proposed to occur in the biosynthesis of trichodiene (Hong, Y. J.; Tantillo, D. J. Org. Lett. 2006, 8, 4601-4604)
13. and abietadiene (Ravn, M. M.; Peters, R. J.; Coates, R. M.; Croteau, R. J. Am. Chem. Soc. 2002, 124, 6998-7006).
14. We have previously found minima with bridging protons in our studies on the biosynthesis of the sesquiterpene pentalenene: (a) Gutta, P.; Tantillo, D. J. J. Am. Chem. Soc. 2006, 128, 6172-6179.
15. (b) Gutta, P.; Tantillo, D. J. Angew. Chem., Int. Ed. 2005, 44, 2719-2723.
16. In ref 4b, semiempirical (AM1) calculations on 3 and 4 were described, but no computed transition structures were reported. This report did, however, suggest that direct proton transfer to form 4 was geometrically feasible.
17. HF/6-31G(d) calculations on 3, 4, and 6 (but not the transition structures between them) were described previously; their relative energies spanned a range of <4 kcal/mol. See: Tokiwano, T.; Endo, T.; Tsukagoshi, T.; Goto, H.; Fukushi, E.; Oikawa, H. Org. Biomol. Chem. 2005, 3, 2713-2722. Although the 3 to 6 rearrangement was mentioned in this paper, it was not proposed as a route to taxa-4,11-diene (i.e., that 6 could go on to 4). A similar proton transfer was also proposed as a route to a fluoroverticellitriene from 6-fluoro-GGPP; see ref 1c.
18. Tunneling may also contribute in these reactions. For related examples and leading references, see: Nagel, Z. D.; Klinman, J. P. Chem. Rev. 2006, 106, 3095-3118.
19. Similar studies have proven useful in probing mechanisms for formation of other terpenes. For a review, see: Segura, M. J. R.; Jackson, B. E.; Matsuda, S. P. T. Nat. Prod. Rep. 2003, 20, 304-317.
20. See the Supporting Information and ref 9 for structures of possible byproducts resulting from diversions from 6.
21. See, for example, the following structures in the references indicated: structure 74 in Hanson, J. R. Nat. Prod. Rep. 2002, 19, 125-132,
22. structure 97 in Hanson, J. R. Nat. Prod. Rep. 2000, 17, 165-174,
23. structure 118 in Hanson, J. R. Nat. Prod. Rep. 1996, 13, 59-71,
24. structure 166 in Hanson, J. R. Nat. Prod. Rep. 1994, 11, 265-277,
25. and structure 126 in Hanson, J. R. Nat. Prod. Rep. 1998, 15, 93-106. See also refs 1c and 9 for leading references on verticillatrienes that might also be formed from 6.
26. Note that proton transfers of the 4-to-6 variety, in which other (diastereotopic) protons are transferred, also provide mechanisms of E/Z isomerization of the C=C double bonds in 3, 5, and 6.
27. 9 although some differences in the conformational landscape for 3 are observed at the higher level of theory used herein.
28. Recent crystallographic studies of terpene synthase complexes with carbocation analogues include: (a) Vedula, L. S.; Cane, D. E.; Christianson, D. W. Biochemistry 2005, 44, 12719-12727.
29. (b) Whittington, D. A.; Wise, M. L.; Urbansky, M.; Coates, R. M.; Croteau, R. B.; Christianson, D. W. Proe Natl. Acad. Sci. U.S.A. 2002, 99, 15375-15380.
30. This is another example of a case where the "simplest" or "least-motion" mechanism is not necessarily the lowest energy pathway. For an interesting discussion of such issues, see: Hoffmann, R.; Minkin, V. I.; Carpenter, B. K. HYLE - Int. J. Phil. Chem. 1997, 3, 3-28
31. (reprinted from: Bull. Soc. Chim. Fr. 1996, 133, 117-130).
32. We are pursuing additional calculations aimed at probing specific substrate-active site and substrate-pyrophosphate interactions.