- Ketoreductase/Transaminase, One-Pot, Multikilogram Biocatalytic Cascade Reaction
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A biocatalytic cascade to produce tert-butyl ((2R,4R)-2-methyltetrahydro-2H-pyran-4-yl)carbamate 6 has been demonstrated at the multikilogram scale. In this reaction, a racemic ketone is resolved by reducing the undesired ketone using a ketone reductase (KRED). The reduction is stereospecific for the 2-position of substrate (2S)-ketone leaving the (2R)-ketone unreacted. After the (2S)-ketone has been depleted, a transaminase is added to catalyze the enantioselective transamination of the ketone, resulting in formation of the (2R, 4R)-amine 6. The product is recovered from the aqueous reaction after Boc protection.
- Burns, Michael,Bi, Wenying,Kim, Hui,Lall, Manjinder S.,Li, Chao,O'Neill, Brian T.
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p. 941 - 946
(2021/03/01)
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- CYCLIC SUBSTITUTED IMIDAZO[4,5-C]QUINOLINE DERIVATIVES
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The present invention provides novel cyclic substituted imidazo[4,5- c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof, wherein R1, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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Page/Page column 48; 49
(2018/09/28)
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- NOVEL IMIDAZO[4,5-C]QUINOLINE DERIVATIVES AS LRRK2 INHIBITORS
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The present invention provides novel imidazo[4,5-c]quinoline derivatives of Formula (I), and the pharmaceutically acceptable salts thereof I wherein R1, R2 and R3 are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula I and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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Page/Page column 53; 54; 55
(2018/09/28)
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- Novel Imidazo[4,5-c]Quinoline And Imidazo[4,5-c][1,5]Naphthyridine Derivatives As LRRK2 Inhibitors
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The present invention provides novel imidazo[4,5-c]quinoline and imidazo[4,5-c][1,5]naphthyridine derivatives of Formula (I), and the pharmaceutically acceptable salts thereof wherein R1, R1a, R1b, R2, R4, R5, R6, X and Z are as defined in the specification. The invention is also directed to pharmaceutical compositions comprising the compounds of Formula (I) and to use of the compounds in the treatment of diseases associated with LRRK2, such as neurodegenerative diseases including Parkinson's disease or Alzheimer's disease, cancer, Crohn's disease or leprosy.
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- Utilizing on- and off-line monitoring tools to follow a kinetic resolution step during flow synthesis
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In situ reaction monitoring tools offer the ability to track the progress of a synthetic reaction in real time to facilitate reaction optimization and provide kinetic/mechanistic insight. Herein, we report the utilization of flow NMR, flow IR, and other off-line spectroscopy tools to monitor the progress of a flow chemistry reaction. The on-line and off-line tools were selected to facilitate the stereoselective kinetic resolution of a key racemic monomer, which lacked a chromophore, making conventional reaction monitoring difficult. Copyright
- Farley, Kathleen A.,Reilly, Usa,Anderson, Dennis P.,Boscoe, Brian P.,Bundesmann, Mark W.,Foley, David A.,Lall, Manjinder S.,Li, Chao,Reese, Matthew R.,Yan, Jiangli
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p. 348 - 354
(2017/03/16)
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- SYNTHESIS OF R-GLUCOSIDES, SUGAR ALCOHOLS, REDUCED SUGAR ALCOHOLS, AND FURAN DERIVATIVES OF REDUCED SUGAR ALCOHOLS
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Disclosed herein are methods for synthesizing 1,2,5,6-hexanetetrol (HTO), 1,6 hexanediol (HDO) and other reduced polyols from C5 and C6 sugar alcohols or R glycosides. The methods include contacting the sugar alcohol or R-glycoside with a copper catalyst, most desirably a Raney copper catalyst with hydrogen for a time, temperature and pressure sufficient to form reduced polyols having 2 to 3 fewer hydoxy groups than the starting material. When the starting compound is a C6 sugar alcohol such as sorbitol or R-glycoside of a C6 sugar such as methyl glucoside, the predominant product is HTO. The same catalyst can be used to further reduce the HTO to HDO.
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Paragraph 0078
(2017/05/31)
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- NOVEL COMPOUNDS
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Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.
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Page/Page column 47
(2015/12/17)
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- ANTI-HIV COMPOUNDS
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Thiazole derivatives represented by Formula (I) are disclosed, where R1, R2, R3, A, X, Y, Z, R6 and R7 are disclosed herein. These thiazole derivatives and pharmaceutical compositions comprising these derivatives are useful in the treatment of HIV mediated diseases and conditions.
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Page/Page column 62; 67
(2009/08/14)
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- The Role of the Nitrogen Atom in the Hydrogenation of Piperidinones and Methylenepiperidines
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Dimethylpiperidinones and dimethylmethylenepiperidines have been hydrogenated over several Group 8, 9 and 10 transition metal catalysts and the stereochemistry of the products compared with those of the carbocyclic analogues.The results obtained suggest that intramolecular interactions between the nitrogen lone pair and the unsaturated bond play a major role in determining the stereochemistry of hydrogenation.
- Senda, Yasuhisa,Okamura, Kazue,Kuwahara, Mayumi,Ide, Masatoshi,Itoh, Hiroki,Ishiyama, Jun-Ichi
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p. 799 - 803
(2007/10/02)
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- BORON TRIFLUORIDE PROMOTED REACTION OF DITHIO-SUBSTITUTED ALLYLIC ANIONS AND CYCLIC ETHERS
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Allylic anions generated from 2-propenyl-1,3-dithiane and 2-styryl-1,3,dithiane react exclusively at α-carbons with three- to six-membered cyclic ethers in the presence of BF3.Et2O.
- Fang, Jim-Min,Chen, Ming-Yi
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p. 5939 - 5940
(2007/10/02)
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- Enzymes in Organic Synthesis. 25. Heterocyclic Ketones as Substrates of Horse Liver Alcohol Dehydrogenase. Highly Stereoselective Reductions of 2-Substituted Tetrahydropyran-4-ones
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Horse liver alcohol dehydrogenase (HLADH) has been found to be an efficient catalyst for the reduction of O-heterocyclic ketones.Preparative-scale HLADH-catalyzed reductions of 2-substituted tetrahydropyran-4-ones are enantioselective, with reduction of e
- Haslegrave, J. Anthony,Jones, J. Bryan
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p. 4666 - 4671
(2007/10/02)
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