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Volumn 128, Issue 18, 2006, Pages 6172-6179

Theoretical studies on farnesyl cation cyclization: Pathways to pentalenene

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME KINETICS; ENZYMES; NUMERICAL ANALYSIS; OLEFINS; POSITIVE IONS; PROTONS;

EID: 33646525410     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja058031n     Document Type: Article
Times cited : (118)

References (101)
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    • (b) Note that covalently bound enzyme-substrate complexes are generally not invoked as intermediates in terpenoid synthase catalyzed reactions, and the putative carbocation rearrangements involved are generally formulated as involving noncovalent enzyme-substrate interactions (steric and/or electrostatic).
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    • (c) With zero-point energies included, the transition structure preceding 8 is actually 0.07 kcal/mol lower in energy than 8 with B3LYP/6-31+G(d,p) and 0.81 kcal/mol higher than 8 with mPW1PW91/ 6-31+G(d,p)//B3LYP/6-31+G(d,p), and the transition structure following 8 is 0.98 kcal/mol higher in energy than 8 with B3LYP/6-31+G(d,p) and 2.00 kcal/mol higher than 8 with mPW1PW91/6-31+G(d,p) //B3LYP/ 6-31+G(d,p).
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    • (c) IRC plots are available in the Supporting Information.
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    • 2+; see, for example, ref 6. Kinetic studies on related sesquiterpene synthases have suggested that this ionization may be the slow chemical step in such reactions; see: Cane, D. E.; Chiu, H.-T.; Liang, P.-H.; Anderson, K. S. Biochemistry 1997, 56, 8332-8339
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    • in press
    • (b) Based on recent experimental (isotope effect) studies, it has been suggested that a discrete farnesyl cation may be avoided in a related cyclization reaction of farnesyl diphosphate: the enzyme catalyzed formation of premnaspirodiene via the germacradienyl cation. See: Schenk, D. J.; Starks, C. M.; Rising Manna, K.; Chappell, J.; Noel, J. P.; Coates, R. M. Arch. Biochem. Biophys., in press.
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    • note
    • A competing [1,2] methyl shift leading to other products is also possible. This reaction and others that may follow it will be described in detail in a separate account.
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    • (a) Cationic [1,2] hydrogen or alkyl shifts generally have very low activation barriers, and in some cases, bridged hypercoordinate structures are actually minima rather than transition structures (so-called nonclassical ions). For leading references, see ref 17.
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    • (b) A small amount of ring strain in the 1-to-2 transition structure likely contributes to the barrier of 6 kcal/mol that we observe in this case.
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    • This reaction can be viewed as an orbital symmetry forbidden all-suprafacial 4-electron (2+2+1) pericyclic reaction (if we think of the reactant as a simple secondary cation we have two C=C π-bonds and an empty p-orbital interacting, but if we think of the reactant as a cyclopropylcarbinyl cation we have a C-C σ-bond, an empty p-orbital, and a C=C π-bond interacting). However, the asynchronicity of bond formation (formation of the five-membered ring leads formation of the four-membered ring) and the relatively long partial C-C bonds in the transition structure suggest that this reaction may actually belong to the class of "apparent violations" of the orbital symmetry rules for which significantly strong overlap of all of the cyclically disposed orbital fragments does not occur at any point along the reaction coordinate. For a related example in a neutral system, see: Kless, A.; Nendel, M.; Wilsey, S.; Houk, K. N. J. Am. Chem. Soc. 1999, 121, 4524-4525
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    • 12 flattens out in the vicinity of structures resembling 3 and 4, but optimization of the final point on the IRC in each direction leads to 7 and 5, respectively. Thus it seems clear that if any minima that flank the transition structure do exist, the barriers for their conversion to 7 and 5 are very small, at least in the absence of an enzyme active site.
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    • 2) on a bicyclic diene precursor of cation 4 (and therefore, we think, of 7) has also been reported to produce pentalenene (in 38% yield); see: Pattenden. G.; Teague, S. J. Tetrahedron 1987, 43, 5637-5652.
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    • note
    • Two other conformers of 1, differing in the spatial disposition of their isoprene units, are also possible. However, these two conformers (below) are actually enantiomers of 1 and 1′. Although these conformers could, in principle, lead to pentalenene with the absolute stereochemistry shown in Scheme 1, such pathways would not be very direct and are not considered further herein. (Diagram presented)
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