65058-52-8Relevant academic research and scientific papers
Method for synthesizing chiral alpha-amino alcohol compound
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Paragraph 0083-0091, (2021/07/28)
The invention discloses a method for synthesizing a chiral alpha-amino alcohol compound. The method comprises the following steps: sequentially adding an iron catalyst, a ligand, ketone, an organic solvent and silane into a reaction system at 20-30 DEG C in a nitrogen atmosphere, then stirring the obtained mixture, and carrying out column chromatography separation on the obtained product to obtain a product, namely chiral alpha-amino alcohol. According to the invention, the most high-yield iron catalyst in earth crust is used, and cheap silane (PMHS, 500 g/298 yuan) is adopted as a reducing agent, so the asymmetric reduction reaction of alpha-amino ketone can be efficiently achieved under mild conditions so as to obtain the high-yield optically-active chiral alpha-amino alcohol compound; and moreover, through the creative labor of the inventor, reaction yield can reach 99%, and meanwhile, the content of the target product in the generated reaction product is 99%.
ZnCl2-promoted asymmetric hydrogenation of β-secondary-amino ketones catalyzed by a P-chiral rh-bisphosphine complex
Hu, Qiupeng,Zhang, Zhenfeng,Liu, Yangang,Imamoto, Tsuneo,Zhang, Wanbin
supporting information, p. 2260 - 2264 (2015/02/19)
A new catalytic system has been developed for the asymmetric hydrogenation of β-secondary-amino ketones using a highly efficient P-chiral bisphosphine-rhodium complex in combination with ZnCl2 as the activator of the catalyst. The chiral γ-secondary-amino alcohols were obtained in 90-94% yields, 90-99% enantioselectivities, and with high turnover numbers (up to 2000 S/C; S/C = substrate/catalyst ratio). A mechanism for the promoting effect of ZnCl2 on the catalytic system has been proposed on the basis of NMR spectroscopy and HRMS studies. This method was successfully applied to the asymmetric syntheses of three important drugs, (S)-duloxetine, (R)-fluoxetine, and (R)-atomoxetine, in high yields and with excellent enantioselectivities.
Optimization of immobilization conditions of Mucor miehei lipase onto Florisil via polysuccinimide spacer arm using response surface methodology and application of immobilized lipase in asymmetric acylation of 2-amino-1-phenylethanols
Yildirim, Deniz,Tuekel, S. Seyhan,Alptekin, Oezlem,Alagoez, Dilek
, p. 91 - 103 (2014/01/17)
In this study, the immobilization of Mucor miehei lipase onto Florisil support via polysuccinimide spacer arm was scrutinized by using a 3-factor and 3-level Box-Behnken design. The independent parameters were immobilization pH, immobilization time and initial lipase concentration and the response was the specific activity of immobilized lipase. A quadratic equation was used to explain the relationship between the response and independent parameters. After analysis of variance test, coefficient of determination and adjusted coefficient of determination values were estimated as 0.98 and 0.94, respectively. The optimal immobilization pH, immobilization time and initial lipase concentration were determined as 6.0, 7 h and 1.1 mg mL-1, respectively, after desirability analysis. The specific activity values for three individual experiments were observed as 25.88 ± 0.73, 26.06 ± 0.47 and 25.96 ± 0.52 U mg protein-1 under the optimized conditions. The hydrolytic activities of free and immobilized lipase preparations were characterized using p-nitrophenyl palmitate as substrate. The esterification activity of immobilized lipase preparation was evaluated by asymmetric acylation of 2-(methylamino)-1-phenylethanol, 2-(ethylamino)-1- phenylethanol, 2-(butylamino)-1-phenylethanol, and 2-(hexylamino)-1- phenylethanol with vinyl acetate. The acylation protocol was optimized in terms of the effects of initial water amount, reaction temperature, molar ratio of amino alcohol to vinyl acetate, biocatalyst loading, organic medium and kind of lipases used. The developed protocol provided a facile methodology for the preparation of enantiopure 2-amino-1-phenylethanols which may be used as potential new β-adrenergic receptor antagonists.
Immobilized Pseudomonas sp. lipase: A powerful biocatalyst for asymmetric acylation of (±)-2-amino-1-phenylethanols with vinyl acetate
Yildirim, Deniz,Tükel, S. Seyhan
, p. 819 - 830 (2013/07/27)
Pseudomonas sp. lipase was immobilized onto glutaraldehyde-activated Florisil support via Schiff base formation and stabilized by reducing Schiff base with sodium cyanoborohydride. The immobilization performance was evaluated in terms of bound
Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors
Langford, H. Marie,Williams, Peter D.,Homnick, Carl F.,Vacca, Joseph P.,Felock, Peter J.,Stillmock, Kara A.,Witmer, Marc V.,Hazuda, Daria J.,Gabryelski, Lori J.,Schleif, William A.
, p. 721 - 725 (2008/12/23)
A series of 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides was synthesized and tested for their inhibition of HIV-1 integrase catalytic activity and HIV-1 replication in cells. Structure-activity studies around lead compound 5 indicated that a coplanar relationship of metal-binding heteroatoms provides optimal binding to the integrase active site. Identification of potency-enhancing substituents and adjustments in lipophilicity provided 17b which inhibits integrase-catalyzed strand transfer with an IC50 value of 74 nM and inhibits HIV-1 replication in cell culture in the presence of 50% normal human serum with an IC95 value of 63 nM.
2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases
Schnute, Mark E.,Anderson, David J.,Brideau, Roger J.,Ciske, Fred L.,Collier, Sarah A.,Cudahy, Michele M.,Eggen, MariJean,Genin, Michael J.,Hopkins, Todd A.,Judge, Thomas M.,Kim, Euibong J.,Knechtel, Mary L.,Nair, Sajiv K.,Nieman, James A.,Oien, Nancee L.,Scott, Allen,Tanis, Steven P.,Vaillancourt, Valerie A.,Wathen, Michael W.,Wieber, Janet L.
, p. 3349 - 3353 (2008/02/07)
A novel series of 2-aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potent antivirals against human herpesviruses. These compounds demonstrate broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with high specificity compared to human DNA polymerases.
Asymmetric hydrogenation of α-primary and secondary amino ketones: Efficient asymmetric syntheses of (-)-arbutamine and (-)-denopamine
Shang, Gao,Liu, Duan,Allen, Scott E.,Yang, Qin,Zhang, Xumu
, p. 7780 - 7784 (2008/04/03)
Two ss-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities by asymmetric hydrogenation of unprotected amino ketones for the first time by using Rh catalysts bearing electron-donating phosphine ligands. A series of α-primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and with good enantioselectivies. This Rh electron-donating phosphine-catalyzed asymmetric hyderogenation repI resents one of the most promising and convenient approaches towards the asymmetric synthesis of chiral amino alcohols.
Solvent and in situ catalyst preparation impacts upon Noyori reductions of aryl-chloromethyl ketones: application to syntheses of chiral 2-amino-1-aryl-ethanols
Tanis, Steven P.,Evans, Bruce R.,Nieman, James A.,Parker, Timothy T.,Taylor, Wendy D.,Heasley, Steven E.,Herrinton, Paul M.,Perrault, William R.,Hohler, Richard A.,Dolak, Lester A.,Hester, Matthew R.,Seest, Eric P.
, p. 2154 - 2182 (2007/10/03)
As part of medicinal chemistry efforts we found it necessary to develop general syntheses of highly enantiomerically enriched 1-aryl-2-chloroethanols and 1-aryl-2-methylaminoethanols. A survey of literature methods suggested that a truly general approach had not yet been reported, encouraging us to undertake the development of such a methodology. This study describes the design, development, and reduction to practice of a general synthesis of chiral 1-aryl-2-chloroethanols and the transformation of these entities to highly enantiomerically enriched 1-aryl-2-methylaminoethanols. Of particular importance were observations of the impact of solvent and the method of catalyst preparation on the yield and enantiomerical excess of chlorohydrins prepared via Noyori transfer hydrogenations of aryl-chloromethyl ketones.
Stereoselective synthesis of (1R)- and (1R,2S)-1-aryl-2-alkylamino alcohols from (R)-cyanohydrins
Effenberger, Franz,Gutterer, Beate,Jaeger, Juergen
, p. 459 - 467 (2007/10/03)
Hydrogenation of (R)-cyanohydrins (R)-1 with LiAlH4 occurs without racemization to give the (R)-2-amino alcohols (R)-3. (1R,2S)-2-Amino alcohols (1R,2S)-4 are obtained with high diastereoselectivity by addition of methyl Grignard to O-silyl protected cyanohydrins (R)-2 and subsequent hydrogenation with NaBH4. The N-alkylated 2-amino alcohols (R)-8 and (1R,2S)-9 can be prepared either by reductive alkylation of the corresponding 2-amino alcohols (R)-3 and (1R,2S)-4, respectively, or by a transimination reaction of the Grignard addition products with primary amines and subsequent hydrogenation with NaBH4. The lower diastereoselectivity of hydrogenation in case of the N-alkylmino compounds in comparison to the N-unsubstituted imines is explained by a weaker chelating effect.
ENANTIOSPECIFIC SYNTHESIS OF (+)-(R)-1-PHENYL-3-METHYL-1,2,4,5-TETRAHYDROBENZAZEPINE FROM (+)-(S)-N-METHYL-1-PHENYL ETHANOLAMINE (HALOSTACHINE) via ARENE CHROMIUM TRICARBONYL METHODOLOGY
Coote, Steven J.,Davies, Stephen G.,Middlemiss, David,Naylor, Alan
, p. 3581 - 3584 (2007/10/02)
Acid promoted cyclisation of homochiral (R)-N-(3,4-dimethoxyphenethyl) halostachine chromium tricarbonyl is stereospecific, proceeding with retention of configuration, to afford, after decomplexation, homochiral (+)-(R)-1-phenyl-3-methyl-1,2,4,5-tatrahydr
