- Biocatalytic Characterization of Human FMO5: Unearthing Baeyer-Villiger Reactions in Humans
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Flavin-containing mono-oxygenases are known as potent drug-metabolizing enzymes, providing complementary functions to the well-investigated cytochrome P450 mono-oxygenases. While human FMO isoforms are typically involved in the oxidation of soft nucleophiles, the biocatalytic activity of human FMO5 (along its physiological role) has long remained unexplored. In this study, we demonstrate the atypical in vitro activity of human FMO5 as a Baeyer-Villiger mono-oxygenase on a broad range of substrates, revealing the first example to date of a human protein catalyzing such reactions. The isolated and purified protein was active on diverse carbonyl compounds, whereas soft nucleophiles were mostly non- or poorly reactive. The absence of the typical characteristic sequence motifs sets human FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism.
- Fiorentini, Filippo,Geier, Martina,Binda, Claudia,Winkler, Margit,Faber, Kurt,Hall, Mélanie,Mattevi, Andrea
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p. 1039 - 1048
(2016/05/19)
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- Stereocontrolled total synthesis of (-)-englerin A
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The total synthesis of (-)-englerin A, a potent and selective inhibitor of renal cancer cell lines, is described. The key feature includes the stereocontrolled construction of the cyclopentane structure by taking advantage of a base-promoted epoxynitrile cyclization.
- Takahashi, Keisuke,Komine, Keita,Yokoi, Yuichi,Ishihara, Jun,Hatakeyama, Susumi
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p. 7364 - 7370
(2012/10/29)
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- Production process for 16-dehydropregnenoneol and its analogs
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The present invention relates to a clean process for the degradation of steroidal sapogenin to produce 16-dehydropregnenolone and its analogs. The pure or the crude pseudo steroidal sapogenin, derived from steroidal sapogenin, dissolved in organic solvent, reacts with hydrogen peroxide with or without metal compound and acid as catalyst, and the crude products directly go through elimination and hydrolization in the presence of base to give 16-Dehydropregnenolone or its analog, accompanied with the other product 4R(or S)-methyl-5-hydroxy-pentate, which is converted to 4R(or S)-methyl-δ-pentyl lactone after acidification and extraction from the water layer. This technology improved the utilizing degree of steroidal sapogenin, improved the yield, and cleared up the chromium pollution in the former technique. In a word, the method disclosed in this invention is more suitable for manufacture.
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Page/Page column 5
(2008/06/13)
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- Novel synthesis of (4R)-4-methylpentanolide from (L)-(-)-menthol
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A novel synthesis of the promising optically pure chiral (4R)-4-methylpentanolide that is based on several regiospecific oxidative transformations of (4R)-2,4-dimethyl-1-(1-methylethyl)-1-cyclohexene, the product of addition of (-)-menthone and methylmagn
- Ishmuratov,Yakovleva,Zaripova,Botsman,Muslukhov,Tolstikov
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p. 548 - 551
(2007/10/03)
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- Access to optically pure 4- and 5-substituted lactones: A case of chemical-biocatalytical cooperation
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Optically pure or highly enantiomerically enriched 4- and 5-substituted lactones are rather difficult to obtain. Chemical or enzymatic syntheses alone are not particularly successful. A combination of chemical catalysis and biocatalysis, however, provides a convenient route to a variety of these useful chiral compounds. In this paper we describe the synthesis of several optically pure 4- and 5-substituted lactones obtained via whole cell-catalyzed Baeyer-Villiger oxidations of highly enantiomerically enriched 3-alkyl cyclic ketones. Such chiral ketones are readily accessed by recently developed copper-catalyzed asymmetric conjugate reductions of the corresponding enones. A very high proximal regioselectivity and complete chirality transfer was obtained by employing biological Baeyer-Villiger oxidations, using recombinant E. coli strains that overexpress cyclopentanone monooxygenase (CPMO). A comparative study showed that CPMO gives superior results to those obtained with cyclohexanone monooxygenase (CHMO) catalyzed oxidations.
- Wang, Shaozhao,Kayser, Margaret M.,Jurkauskas, Valdas
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p. 6222 - 6228
(2007/10/03)
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- Enzymes in Organic Synthesis, 21. Lipase-Catalyzed Conversion of (+/-)-2-Methylglutaric Anhydride into (S)-2-Methyl- and (R)-4-Methyl-δ-valerolactone via a Regio- and Enantioselective Sequential Esterification
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The enzyme-catalyzed sequential esterification of (+/-)-2-methylpentanedioic anhydride (rac-1) with 2-methylpropanol in diethyl ether afforded a 1:1 mixture of 1-(2-methylpropyl) 5-hydrogen (S)-4-methylpentanedioate (ent-2) with an enantiomeric excess of 88percent and 1-(2-methylpropyl) 5-hydrogen (R)-2-methylpentanedioate (3) with an e.e. of 99percent besides a considerable amount of the diester ent-4.Exploiting the ability of the enzymes Novozym and SP 382 to differentiate between the two enantiomers and to catalyze the alcoholysis of both enantiomers with opposite regioselectivity, we reduced the resolution of rac-1 to a simple chromatographic separation of enantiomerically enriched regioisomeric monoesters.The high optical purity of monoester 3 could be achieved due to the fast conversion of its enantiomer into the diester ent-4.Via reduction with lithium borohydride the monoesters ent-2 and 3 were converted into the corresponding δ-valerolactones ent-5 and 6. - Key Words: Enzymes / Pentanedioic anhydride, 2-methyl / Alcoholysis, enantio- and regioselective / Esterification sequential
- Ozegowski, Ruediger,Kunath, Annamarie,Schick, Hans
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p. 1019 - 1024
(2007/10/02)
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