1044833-25-1Relevant articles and documents
Preparation of enantiomerically enriched aromatic β-hydroxynitriles and halohydrins by ketone reduction with recombinant ketoreductase KRED1-Pglu
Contente, Martina L.,Serra, Immacolata,Molinari, Francesco,Gandolfi, Raffaella,Pinto, Andrea,Romano, Diego
, p. 3974 - 3979 (2016)
A NADPH-dependent benzil reductase (KRED1-Pglu) was used as recombinant enzyme for catalysing the reduction of different functionalised ketones. The reactions were carried out in the presence of a catalytic amount of NADP+and an enzyme-coupled transformation (oxidation of glucose catalysed by glucose dehydrogenase), for regenerating the cofactor and thus driving the reaction to completion. KRED1-Pglu showed remarkable versatility, being able to reduce different β-ketonitriles and α-haloketones at different pHs; notably, depending on the nature of the substrate, KRED1-Pglu can be used for efficient and clean enzymatic reduction, avoiding side-reactions due to the pH of the medium. The reduction generally occurred with high enantioselectivity, allowing the preparation of enantiomerically enriched β-hydroxynitriles and halohydrins in high yields; the stereochemical outcome of the reduction followed in all the cases the so-called Prelog's rule.
Efficient methodology to produce a duloxetine precursor using whole cells of Rhodotorula rubra
Rimoldi, Isabella,Facchetti, Giorgio,Nava, Donatella,Contente, Martina Letizia,Gandolfi, Raffella
, p. 389 - 396 (2016)
Different types of yeasts were employed as biocatalysts in the reduction of β-ketonitriles. The red microorganism, Rhodotorula rubra, was selected as the best performing catalyst in the reduction of different substituted ketonitriles giving total stereoselectivity in most cases (90-99% ee). In particular, its use as fresh and lyophilised cells was expanded to a semi-preparative scale for the production of the duloxetine precursor 1a. R. rubra was screened in the reduction of alkylation products in comparison with Pichia henricii for assignment of configuration of products 2a and 11a after derivatisation with S-MPA.
Novel Thienopyrimidones
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Paragraph 0117-0121; 0122, (2021/04/17)
This invention relates to thienopyrimidinones and their use as inhibitors of TRPA1 activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of fibrotic diseases, inflammatory and auto-immune diseases and CNS-related diseases.
Halohydrin dehalogenase-catalysed synthesis of fluorinated aromatic chiral building blocks
Dokli, Irena,Mil?i?, Nevena,Marin, Petra,Mikleni?, Marina Svetec,Sudar, Martina,Tang, Lixia,Bla?evi?, Zvjezdana Findrik,Elenkov, Maja Majeri?
, (2021/02/02)
Kinetic resolution of a series of fluorinated styrene oxide derivatives was studied using halohydrin dehalogenase. A mutant HheC-W249P catalysed nucleophilic ring-opening with azide and cyanide ions with excellent enantioselectivity (E-values up to >200), which gives access to various enantiopure β-substituted alcohols and epoxides. It was found that the enzyme tolerates substrates in concentrations over 50 mM. However, different side reactions were observed at elevated concentrations and with prolonged reaction time. The biocatalytic azidolysis and cyanolysis of racemic 4-trifluoromethylstyrene oxide were performed on preparative scale, affording (R)-2-azido-1-(4-trifluoromethyl-phenyl)-ethanol in 38% yield and 97% ee, and (S)-3-hydroxy-3-(4-trifluoromethyl-phenyl)-propionitrile in 30% yield and 98% ee.
