19068-48-5Relevant articles and documents
Biocatalytic Asymmetric Hydroxylation of Hydrocarbons with the Topsoil-Microorganism Bacillus megaterium
Adam, Waldemar,Lukacs, Zoltan,Harmsen, Dag,Saha-Moeller, Chantu R.,Schreier, Peter
, p. 878 - 882 (2000)
A Bacillus megaterium strain was isolated from topsoil by a selective screening procedure with allylbenzene as a xenobiotic substrate. This strain performed the hydroxylation chemoselectively (no arene oxidation and overoxidized products) and enantioselectively (up to 99% ee) in the benzylic and nonbenzylic positions of a variety of unfunctionalized arylalkanes. Salycilate and phenobarbital, which are potent inducers of cytochrome P-450 activity, changed the regioselectivity of the microbial CH insertion, without an effect on the enantioselectivity. The biotransformation conditions were optimized in regard to product yield and enantioselectivity by variation of the oxygen-gas supply and the time of the substrate addition. The different product distributions (α- versus β-hydroxylated product) that are obtained on induction of cytochrome P-450 enzyme activity demonstrate the involvement of two or more hydroxylating enzymes with distinct regioselectivities in this biotransformation. An oxygen-rebound mechanism is assumed for the cytochrome P-450-type monooxygenase activity, in which steric interactions between the substrate and the enzyme determine the preferred face of the hydroxy-group transfer to the radical intermediate.
Dynamic Reductive Kinetic Resolution of Benzyl Ketones using Alcohol Dehydrogenases and Anion Exchange Resins
Méndez-Sánchez, Daniel,Mangas-Sánchez, Juan,Busto, Eduardo,Gotor, Vicente,Gotor-Fernández, Vicente
, p. 122 - 131 (2016/01/25)
Dynamic reductive kinetic resolutions of racemic 3-arylalkanones have been performed by the proper combination of an alcohol dehydrogenase and a basic anionic resin. The best results were found for the bioreduction with the alcohol dehydrogenase type A from Rhodococcus ruber DSM 44541 overexpressed in Escherichia coli (E. coli/ADH-A) and the commercially available evo-1.1.200, while the Amberlite IRA-440 C and the DOWEX-MWA-1 resins allowed efficient in situ racemizations. Reaction conditions were optimized in terms of enzyme source and loading, type and amount of resin, pH, temperature and reaction times, obtaining a series of (R,R)-substituted propan-2-ols with good conversions and both diastereoselectivity and stereoselectivity. As a proof of concept, the subsequent intramolecular cyclization of a selected propan-2-ol substrate afforded a valuable isochroman heterocycle without any loss of the optical purity.
Enantiopreference of Lipase from Pseudomonas cepacia toward Primary Alcohols
Weissfloch, Alexandra N. E.,Kazlauskas, Romas J.
, p. 6959 - 6969 (2007/10/03)
We propose an empirical rule that predicts which enantiomer of primary alcohol reacts faster in reactions catalyzed by lipase from Pseudomonas cepacia (PCL).This rule, based on the size of the substituents at the stereocenter, shows an 89percent reliability (correct for 54 of 61 examples).This rule is not reliable for primary alcohols that have an oxygen atom attached to the stereocenter; we excluded these alcohols from the tally above.Surprisingly, the sense of enantiopreference of PCL toward primary alcohols is opposit to its enantiopreference toward secondary alcohols.That is, the OH of secondary alcohols and the CH2OH of primary alcohols point in opposite directions.We suggest, however, that this opposite orientation does not imply a different position of the substituents in the active site of the lipase.Instead, PCL accommodates the extra CH2 in primary alcohols as a kink between the stereocenter and the oxygen which allows a similar position of the alcohols by increasing the diffrence in the size of the substituents but did not find a consistent increase in enantioselectivity.We suggest that high enantioselectivity toward primary alcohols requires not only a significant difference in the size of the substituents, but also control of the conformation along the C(1)-C(2) bond.
