- Biocatalytic access to nonracemic γ-oxo esters: Via stereoselective reduction using ene-reductases
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The asymmetric bioreduction of α,β-unsaturated γ-keto esters using ene-reductases from the Old Yellow Enzyme family proceeds with excellent stereoselectivity and high conversion levels, covering a broad range of acyclic and cyclic derivatives. Various strategies were employed to provide access to both enantiomers, which are versatile precursors of bioactive molecules. The regioselectivity of hydride addition on di-activated alkenes was elucidated by isotopic labeling experiments and showed strong preference for the keto moiety as activating/binding group as opposed to the ester. Finally, chemoenzymatic synthesis of (R)-2-(2-oxocyclohexyl)acetic acid was achieved in high ee on a preparative scale combining enzymatic reduction followed by ester hydrogenolysis.
- Turrini, Nikolaus G.,Cioc, Rǎzvan C.,Van Der Niet, Daan J. H.,Ruijter, Eelco,Orru, Romano V. A.,Hall, Mélanie,Faber, Kurt
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p. 511 - 518
(2017/08/14)
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- Biocatalytic synthesis of chiral cyclic γ-oxoesters by sequential C-H hydroxylation, alcohol oxidation and alkene reduction
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A three-step biocatalytic procedure is described for the conversion of methyl and ethyl cyclopentene- and cyclohexenecarboxylates into both the enantiomers of the corresponding chiral 3-oxoesters, which are useful building blocks for the synthesis of active pharmaceutical ingredients. The allylic hydroxylation of the starting cycloalkenecarboxylates is carried out by using R. oryzae resting cells entrapped in alginate beads, in acetate buffer solution at 25 °C. The oxidation of the intermediate allylic alcohols to unsaturated ketones, performed by the laccase/TEMPO system, and the ene-reductase mediated hydrogenation of the alkene bond were carried out in the same reaction vessel in a sequential mode at 30 °C. Being entirely biocatalytic, our multistep procedure provides considerable advantages in terms of selectivity and environmental impact over reported chemical methods.
- Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Monti, Daniela,Parmeggiani, Fabio,Pugliese, Andrea,Tentori, Francesca
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supporting information
p. 5122 - 5130
(2017/11/09)
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- Synthesis of gem-difluorocyclopentane/hexane building blocks
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An approach to the preparation of gem-difluorocyclopentane/hexane-derived carboxylic acids and amines is described. Whereas for 3,3-difluoro-substituted cycloalkanones, straightforward deoxofluorination of the corresponding ketoesters led to the target compounds, in the case of 2,2-difluoro isomers, the bypass or alternative routes were necessary.
- Melnykov, Kostiantyn P.,Nosik, Pavel S.,Kurpil, Bohdan B.,Sibgatulin, Dmitriy A.,Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Grygorenko, Oleksandr O.
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- Glutaminase inhibitors as well as compositions and applications thereof
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The invention provides a series of heterocyclic compounds expressed in a formula I. The compound comprises glutaminase inhibition activity, and can be used for treating diseases and symptoms related to dysfunction of glutaminase or raising activity of glutaminase.
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Paragraph 0409; 0411; 0465; 0466; 0467; 0468
(2018/01/09)
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- POLYFLUORINATED COMPOUNDS ACTING AS BRUTON TYROSINE KINASE INHIBITORS
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Described herein is a novel series of multi-fluoro-substituted pyrazolopyrimidine compounds or salts thereof. These compounds are Bruton's tyrosine kinase (BTK) inhibitors. These compounds may possess better BTK inhibition selectivity and pharmacokinetic properties. Disclosed herein are the synthesis methods of these compounds. Disclosed herein are novel synthesis methods of the multi-fluoro-substituted benzophenone and substituted phenoxy benzene. Also disclosed are pharmaceutical compositions comprising the BTK inhibitors described herein. The present invention also relates to pharmaceutical formulations comprising the compounds described herein as active ingredients. The present invention also includes the therapeutic methods by administering the BTK inhibitors and their formulations to treat and inhibit autoimmune disease, hypersensitivity disease, inflammatory diseases and cancer.
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Paragraph 0443; 0444
(2016/08/17)
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- Substituent effect on the photochemistry of 4,4-dialkoxylated- and 4-hydroxylated cyclohexenones
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Photochemistry of the title compounds in various solvents was studied using a broad band of light centered at 350 nm. C-4 spiroketal cyclohexenone 4 (1.0 M) afforded dimers and 12b with the predominance of the former in polar solvent and the latter in non
- Chen, Yu-Jen,Wang, Hui-Ling,Villarante, Nelson R.,Chuang, Gary Jing,Liao, Chun-Chen
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p. 9591 - 9599
(2013/10/22)
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- Substituted Amide Compounds
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Substituted amide compounds corresponding to formula I: processes for preparing them, pharmaceutical compositions containing these compounds, and the use of substituted amide derivatives for the preparation of medicaments for the treatment of pain and various other conditions.
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Page/Page column 48
(2009/01/20)
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