title: Delocalization of charge and electron density in the humulyl cation—implications for terpene biosynthesis.
abstract: The stabilizing features of a macrocyclic sesquiterpene-derived cation were explored using quantum mechanical calculations. The monocyclic humulyl cation, the product of 11,1-cyclization of farnesyl diphosphate, is the product of the first committed step in the enzymatic synthesis of a range of structurally diverse sesquiterpenes, including humulene (monocyclic); caryophyllene (bicyclic); and protoilludene, pentalenene, and isocomene (tricyclic). These natural products are formed via carbocation cascades that are directed in part by the conformation of the humulyl cation. Understanding the mechanistic details of product formation requires an understanding of the conformational preferences of this fundamental intermediate. Replacing the carbocation with borane (preserving π-accepting capabilities), ammonium (preserving positive charge), and methylene (preserving neither π-accepting capabilities nor charge) provides a systematic method to distinguish electrostatic and orbital effects on structure and internal stabilization. Several modes of internal stabilization—hyperconjugation, transannular π(alkene)···C(+) and transannular C-H···C(+) interactions—were uncovered, confirming and extending previous studies on this and similar systems.
authors.affiliation: ‡Department of Chemistry and Biochemistry, Albright College, 13th and Bern Streets, Reading, Pennsylvania 19604, United States.
authors.forename: Trevor A
authors.initials: TA
authors.lastname: Hamlin
authors.affiliation: ‡Department of Chemistry and Biochemistry, Albright College, 13th and Bern Streets, Reading, Pennsylvania 19604, United States.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hamann
authors.affiliation: §Department of Chemistry, University of California-Davis, 1 Shields Avenue, Davis, California 95616, United States.
authors.forename: Dean J
authors.initials: DJ
authors.lastname: Tantillo
mesh_terms: D002412:Cations / Q000737:chemistry*; D003500:Cyclization; D004583:Electrons; D006860:Hydrogen Bonding; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008968:Molecular Conformation; D000081222:Monocyclic Sesquiterpenes; D000081223:Polycyclic Sesquiterpenes; D011106:Polyisoprenyl Phosphates / Q000737:chemistry*; D011789:Quantum Theory; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D002412:Cations; D047028:Macrocyclic Compounds; D000081222:Monocyclic Sesquiterpenes; D000081223:Polycyclic Sesquiterpenes; D011106:Polyisoprenyl Phosphates; D012717:Sesquiterpenes; C042686:humulene; C004808:farnesyl pyrophosphate; C024714:caryophyllene