The rabbit liver microsomal biotransformation of 1,1-dialkylethylenes: enantioface selection of epoxidation and enantioselectivity of epoxide hydrolysis.
The rabbit liver microsomal biotransformation of alpha-methylstyrene (1a), 2-methyl-1-hexene (1b), 2,4,4-trimethyl-1-pentene (1c), and 1,3,3-trimethyl-1-butene (1d) has been investigated with the aim at establishing the enantioface selection of the cytochrome P-450-promoted epoxidation of the double bond and the enantioselectivity of microsomal epoxide hydrolase(mEH)-catalyzed hydrolysis of the resulting epoxides. GLC on a Chiraldex G-TA (ASTEC) column was used to determine the enantiomeric composition of the products. The epoxides 2 first produced in incubations carried out in the presence of an NADPH regenerating system were not detected, being rapidly hydrolyzed by mEH to diols 3. The enantiomeric composition of the latter showed that no enantioface selection occurred in the epoxidation of 1c and 1d, and a very low (8%) ee of the (R)-epoxide was formed from 1b. Incubation of racemic epoxides 2b-d with the microsomal fraction showed that the mEH-catalyzed hydrolysis of 2c and 2d was practically nonenantioselective, while that of 2b exhibited a selectivity E = 4.9 favoring the hydrolysis of the (S)-enantiomer. A comparison of these results with those previously obtained for linear and branched chain alkyl monosubstituted oxiranes shows that the introduction of the second alkyl substituent suppresses the selectivity of the mEH reaction of the latter and reverses that of the former substrates.
Department of Bioorganic Chemistry, University of Pisa, Italy.
G
G
Bellucci
C
C
Chiappe
A
A
Cordoni
F
F
Marioni
D000475:Alkenes / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D004852:Epoxy Compounds / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D011817:Rabbits; D013237:Stereoisomerism; D013379:Substrate Specificity
D000475:Alkenes; D004852:Epoxy Compounds; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases