33758-15-5Relevant academic research and scientific papers
Identification of a Robust Carbonyl Reductase for Diastereoselectively Building syn-3,5-Dihydroxy Hexanoate: A Bulky Side Chain of Atorvastatin
Gong, Xu-Min,Zheng, Gao-Wei,Liu, You-Yan,Xu, Jian-He
supporting information, p. 1349 - 1354 (2017/09/23)
t-Butyl-6-cyano-(3R,5R)-dihydroxyhexanoate is an advanced chiral precursor for the synthesis of the side chain pharmacophore of cholesterol-lowering drug atorvastatin. Herein, a robust carbonyl reductase (LbCR) was newly identified from Lactobacillus brevis, which displays high activity and excellent diastereoselectivity toward bulky t-butyl 6-cyano-(5R)-hydroxy-3-oxo-hexanoate (7). The engineered Escherichia coli cells harboring LbCR and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of substrate 7. As a result, as much as 300 g L-1 of water-insoluble substrate was completely converted to the corresponding chiral diol with >99.5% de in a space-time yield of 351 g L-1 d-1, indicating a great potential of LbCR for practical synthesis of the very bulky and bi-chiral 3,5-dihydroxy carboxylate side chain of best-selling statin drugs.
A novel P450-based biocatalyst for the selective production of chiral 2-alkanols
Von Bühler, Clemens J.,Urlacher, Vlada B.
supporting information, p. 4089 - 4091 (2014/04/03)
A P450 monooxygenase from Nocardia farcinica (CYP154A8) catalyses the stereo- and regioselective hydroxylation of n-alkanes, still a challenging task in chemical catalysis. In a biphasic reaction system, the regioselectivity for the C2-position of C7-C9 alkanes was over 90%. The enzyme showed strict S-selectivity for all tested substrates, with enantiomeric excess (ee) of up to 91%. This journal is the Partner Organisations 2014.
Continuous biphasic enzymatic reduction of aliphatic ketones
Leuchs, Susanne,Nonnen, Thomas,Dechambre, Dominique,Na'Amnieh, Shukralla,Greiner, Lasse
, p. 52 - 59 (2013/08/24)
Biphasic reactions offer an attractive alternative for the utilisation of enzymes for conversion of hardly water soluble substrates. Especially, the alcohol dehydrogenase from Lactobacillus brevis was successfully used for the reductive synthesis of enantiopure secondary aliphatic alcohols. With the enzymatic catalyst and the cofactor effectively retained in the reactive aqueous phase, the continuous operation was demonstrated by continuous addition and withdrawal of the non-reactive phase. The four tested substrates 2-heptanone, 2-octanone, 2-nonanone, and 2-decanone showed that the space time yield and turnover numbers (TON) of the enzyme decrease as the availability of the substrate decreases with increasing partition coefficients. Nevertheless, a TONLbADH of up to 478 × 103 could be achieved. Remarkably, the cofactor utilisation turned out to be very high and a TON NADP+ of more than 20 × 103 was easily achievable for both 2-heptanone and 2-octanone by substrate coupled cofactor regeneration with excess of 2-propanol.
Catalytic enantioselective addition of alkyl grignard reagents to aliphatic aldehydes
Fernandez-Mateos, Emilio,Macia, Beatriz,Yus, Miguel
supporting information, p. 1249 - 1254 (2013/06/27)
Herein, we report an efficient catalytic system for the enantioselective addition of alkyl Grignard reagents to a broad range of aliphatic aldehydes with good yields and enantioselectivities. Remarkably, the challenging methylmagnesium bromide (MeMgBr) can also be added to a variety of aliphatic aldehydes, providing versatile chiral methyl carbinol units with unprecedented yields and enantioselectivities in a simple one-pot procedure under mild conditions. Copyright
Stereospecific inversion of secondary tosylates to yield chiral methyl-branched building blocks, applied to the asymmetric synthesis of leafminer sex pheromones
Taguri, Tomonori,Yamakawa, Rei,Fujii, Toru,Muraki, Yuta,Ando, Tetsu
experimental part, p. 852 - 858 (2012/09/22)
All four of the possible stereoisomers of 5,9-dimethylheptadecane, the major sex pheromone component secreted by female moths of the mountain-ash bentwing (Leucoptera scitella), were synthesized by the coupling of two chiral blocks with a methyl branch at the 2- or 3-position. The blocks were prepared by applying the stereospecific inversion of secondary tosylates, which were derived from (R)- and (S)-propylene oxide, and their enantiopurities were confirmed by chiral HPLC analysis.
Ionic liquid facilitates biocatalytic conversion of hardly water soluble ketones
Kohlmann, Christina,Robertz, Nora,Leuchs, Susanne,Dogan, Zuebeyde,Luetz, Stephan,Bitzer, Katrin,Na'Amnieh, Shukrallah,Greiner, Lasse
experimental part, p. 147 - 153 (2011/10/08)
Ionic liquids represent a promising alternative to conventional cosolvents as biocompatible solubilisers for biocatalysis. This was shown using water miscible ionic liquids to facilitate the stereoselective reduction of hardly water soluble, aliphatic ketones catalysed by the alcohol dehydrogenase from Lactobacillus brevis. Ten ionic liquids were screened for activity and solubility. Improved storage stabilities besides improved enzyme activities, as well as reduced substrate surplus and product inhibitions were found, while applying the most promising AMMOENG 101 in more detailed investigations. Batch reactions with cofactor regeneration via a glucose dehydrogenase showed increased reaction rates; thus underlining the positive influence of AMMOENG 101. For (R)-3-octanol, (R)-2-nonanol, (R)-2-decanol, and (R)-2-octanol space time yields between 250 and 350 mmol L-1 d -1 were achieved.
Utilising hardly-water soluble substrates as a second phase enables the straightforward synthesis of chiral alcohols
Kohlmann, Christina,Robertz, Nora,Leuchs, Susanne,Greiner, Lasse,Na'Amnieh, Shukralla
supporting information; experimental part, p. 3093 - 3095 (2011/12/05)
So far, the alcohol dehydrogenase-catalysed conversion of longer chain aliphatic substrates has been challenging due to their low solubility in aqueous solution. However, by utilising the ketone directly as a second organic phase, the straightforward synthesis of long chain aliphatic chiral alcohols is enabled. The Royal Society of Chemistry.
Asymmetric anti-Prelog reduction of ketones catalysed by Paracoccus pantotrophus and Comamonas sp. cells via hydrogen transfer
Lavandera, Ivan,Hoeller, Brigitte,Kern, Alexander,Ellmer, Ursula,Glieder, Anton,de Wildeman, Stefaan,Kroutil, Wolfgang
, p. 1954 - 1958 (2008/12/22)
A broad range of ketones including methyl-aryl-, methyl-alkyl-, cyclic and sterically hindered ketones were reduced to the corresponding anti-Prelog alcohols with moderate to excellent stereoselectivities by employing lyophilised cells of Paracoccus pantotrophus DSM 11072 and Comamonas sp. DSM 15091 via hydrogen transfer. The reduction equivalents were provided using 2-propanol as a hydride donor. For instance, acetophenone was reduced to the corresponding (R)-enantiomer with >99% ee.
One-way biohydrogen transfer for oxidation of sec-alcohols
Lavandera, Ivan,Kern, Alexander,Resch, Verena,Ferreira-Silva, Bianca,Glieder, Anton,Fabian, Walter M. F.,De Wildeman, Stefaan,Kroutil, Wolfgang
supporting information; experimental part, p. 2155 - 2158 (2009/05/27)
(Chemical Equation Presented) Quasi-irreversible oxidation of sec-alcohols was achieved via biocatalytic hydrogen transfer reactions using alcohol dehydrogenases employing selected ketones as hydrogen acceptors, which can only be reduced but not oxidized. Thus, only 1 equiv of oxidant was required instead of a large excess. For the oxidation of both isomers of methylcarbinols a single nonstereoselective short-chain dehydrogenase/reductase from Sphingobium yanoikuyae was identified and overexpressed in E. coli.
Orchestration of concurrent oxidation and reduction cycles for stereoinversion and deracemisation of sec-alcohols
Voss, Constance V.,Gruber, Christian C.,Faber, Kurt,Knaus, Tanja,Macheroux, Peter,Kroutil, Wolfgang
supporting information; experimental part, p. 13969 - 13972 (2009/02/07)
Black and white are opposites as are oxidation and reduction. Performing an oxidation, for example, of a sec-alcohol and a reduction of the corresponding ketone in the same vessel without separation of the reagents seems to be an impossible task. Here we show that oxidative cofactor recycling of NADP + and reductive regeneration of NADH can be performed simultaneously in the same compartment without significant interference. Regeneration cycles can be run in opposing directions beside each other enabling one-pot transformation of racemic alcohols to one enantiomer via concurrent enantioselective oxidation and asymmetric reduction employing defined alcohol dehydrogenases with opposite stereo- and cofactor-preference. Thus, by careful selection of appropriate enzymes, NADH recycling can be performed in the presence of NADP+ recycling to achieve overall, for example, deracemisation of sec-alcohols or stereoinversion representing a possible concept for a "green" equivalent to the chemical-intensive Mitsunobu inversion.
