Cytochrome P‐450‐catalyzed asymmetric epoxidation of simple prochiral and chiral aliphatic alkenes: species dependence and effect of enzyme induction on enantioselective oxirane formation

Abstract

The enantioselectivity of the in vitro conversion of simple prochiral and chiral aliphatic alkenes into oxiranes by liver microsomes of untreated or induced (phenobarbital) rats, of untreated or induced (phenobarbital, benzo[a] pyrene) mice, and of humans was determined by complexation gas chromatography. The enantiomeric excess (ee) of the epoxides extends from 0 (trimethyloxirane) to 50% (ethyloxirane). The configuration (R or S) of the enantiomers formed in excess is consistent for homologous oxiranes but is species dependent and in some cases influenced by enzyme induction. Enantioselectivity differences of aliphatic alkene epoxidation by human liver microsomes of four individuals are negligible.

Contributions to the theory and practice of the chromatographic separation of enantiomers

“…These advances were considered as predecessors of the well-known titanium/tartrate system (Katsuki -Sharpless epoxidation) 26 and the manganese(II) -salen system (Jacobsen kinetic resolution). 27 The versatile analytical tool of enantioselective complexation GC also permitted the investigation of the Cytochrome P450-mediated epoxidation of simple prochiral olefins (propene, 1-butene, trans-2-butene) 28 and the kinetic resolution of the oxiranes (methyloxirane, ethyloxirane, trans-2,3-dimethyloxirane) formed by epoxide-hydrolase and glutathion-S-transferase. 28 For the xenobiotic substrate cis-2-ethyl-3-methyloxirane, a totally regio-and enantioselective kinetic resolution to threo-(2R,3R)-2,3-pentanediol with microsomal epoxidehydrolase was found.…”

“…27 The versatile analytical tool of enantioselective complexation GC also permitted the investigation of the Cytochrome P450-mediated epoxidation of simple prochiral olefins (propene, 1-butene, trans-2-butene) 28 and the kinetic resolution of the oxiranes (methyloxirane, ethyloxirane, trans-2,3-dimethyloxirane) formed by epoxide-hydrolase and glutathion-S-transferase. 28 For the xenobiotic substrate cis-2-ethyl-3-methyloxirane, a totally regio-and enantioselective kinetic resolution to threo-(2R,3R)-2,3-pentanediol with microsomal epoxidehydrolase was found. 29 Before the advent of modified cyclodextrins, enantioselective complexation GC also represented a very useful tool for chiral analysis of volatile flavors, fragrances, and insect pheromones.…”

Separation of Enantiomers by Gas Chromatography on Chiral Stationary Phases

“…The possibility of determining the enantiomeric ratio of small chiral aliphatic oxiranes permitted study of the asymmetric epoxidation of simple unfunctionalized olefins and the kinetic resolution of racemic oxiranes by metal catalysts [116] and by microsomal enzymes [127,128]. Gas chromatographic capillary columns coated with modified CDs were used in enzyme and catalyst screening [129][130][131] and for the enantiomeric analysis of different classes of chiral compounds, such as essential oils, flavors and fragrances [86,87,[132][133][134], lactones [135], branched fatty acid esters [136,137], organochlorines [101,138], pollutants [139,140], silicon compounds [141], alkyl nitrates as atmospheric constitutents [110], inhalational anesthetics [142,143], compounds of clinical interest [144,145], α-amino acids for space exploration [146,147], as well as unfunctionalized 1,2-dialkylcyclohexanes [148] and aliphatic hydrocarbons [149][150][151] (see also references 97-105 in [10] and 270 references on pages 222-231 in the book of Schreier et al [16]).…”

Enantio‐ and regioselectivity in the epoxide‐hydrolase‐catalyzed ring opening of aliphatic oxiranes: Part II: Dialkyl‐ and trialkylsubstituted oxiranes

“…The percentages of unchanged oxirane enantiomers were determined by complexation gas chromatography by the head-space technique. 2,4932 Control experiments ensured that the enantiomeric composition in the gas phase corresponded to that in solution. When the substrates were diastereomers, control experiments were performed to determine the correction factor of the diastereomeric ratio in the gas and liquid phases.…”