title: Bisabolyl-derived sesquiterpenes from tobacco 5-epi-aristolochene synthase-catalyzed cyclization of (2Z,6E)-farnesyl diphosphate.
abstract: We report the structures and stereochemistry of seven bisabolyl-derived sesquiterpenes arising from an unprecedented 1,6-cyclization (cisoid pathway) efficiently catalyzed by tobacco 5-epi-aristolochene synthase (TEAS). The use of (2Z,6E)-farnesyl diphosphate as an alternate substrate for recombinant TEAS resulted in a robust enzymatic cyclization to an array of products derived exclusively (>/=99.5%) from the cisoid pathway, whereas these same products account for ca. 2.5% of the total hydrocarbons obtained using (2E,6E)-farnesyl diphosphate. Chromatographic fractionations of extracts from preparative incubations with the 2Z,6E substrate afforded, in addition to the acyclic allylic alcohols (2Z,6E)-farnesol (6.7%) and nerolidol (3.6%), five cyclic sesquiterpene hydrocarbons and two cyclic sesquiterpene alcohols: (+)-2-epi-prezizaene (44%), (-)-alpha-cedrene (21.5%), (R)-(-)-beta-curcumene (15.5%), alpha-acoradiene (3.9%), 4-epi-alpha-acoradiene (1.3%), and equal amounts of alpha-bisabolol (1.8%) and epi-alpha-bisalolol (1.8%). The structures, stereochemistry, and enantiopurities were established by comprehensive spectroscopic analyses, optical rotations, chemical correlations with known sesquiterpenes, comparisons with literature data, and GC analyses. The major product, (+)-2-epi-prezizaene, is structurally related to the naturally occurring tricyclic alcohol, jinkohol (2-epi-prezizaan-7beta-ol). Cisoid cyclization pathways are proposed by which all five sesquiterpene hydrocarbons are derived from a common (7R)-beta-bisabolyl(+)/pyrophosphate(-) ion pair intermediate. The implications of the "cisoid" catalytic activity of TEAS are discussed.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Faraldos
authors.forename: Paul E
authors.initials: PE
authors.lastname: O'Maille
authors.forename: Nikki
authors.initials: N
authors.lastname: Dellas
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Noel
authors.forename: Robert M
authors.initials: RM
authors.lastname: Coates
mesh_terms: D002384:Catalysis; D003500:Cyclization; D015394:Molecular Structure; D000081222:Monocyclic Sesquiterpenes; D011106:Polyisoprenyl Phosphates / Q000737:chemistry*; D011994:Recombinant Proteins / Q000235:genetics; D012717:Sesquiterpenes / Q000737:chemistry* / Q000145:classification; D014026:Nicotiana / Q000201:enzymology*
chemical_list: C108196:5-epi-aristolochene; D000081222:Monocyclic Sesquiterpenes; D011106:Polyisoprenyl Phosphates; D011994:Recombinant Proteins; D012717:Sesquiterpenes; C004497:bisabolol; C004808:farnesyl pyrophosphate