87860-35-3Relevant academic research and scientific papers
PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION
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Page/Page column 163, (2020/01/11)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
Design and Synthesis of N-Aryl Phenoxyethoxy Pyridinones as Highly Selective and CNS Penetrant mGlu3 NAMs
Engers, Julie L.,Bollinger, Katrina A.,Weiner, Rebecca L.,Rodriguez, Alice L.,Long, Madeline F.,Breiner, Megan M.,Chang, Sichen,Bollinger, Sean R.,Bubser, Michael,Jones, Carrie K.,Morrison, Ryan D.,Bridges, Thomas M.,Blobaum, Anna L.,Niswender, Colleen M.,Conn, P. Jeffrey,Emmitte, Kyle A.,Lindsley, Craig W.
, p. 925 - 930 (2017/09/23)
Herein, we detail the optimization of the mGlu3 NAM, VU0650786, via a reductionist approach to afford a novel, simplified mGlu3 NAM scaffold that engenders potent and selective mGlu3 inhibition (mGlu3 IC50
Highly Enantioselective Hydrogenation of Amides via Dynamic Kinetic Resolution Under Low Pressure and Room Temperature
Rasu, Loorthuraja,John, Jeremy M.,Stephenson, Elanna,Endean, Riley,Kalapugama, Suneth,Clément, Roxanne,Bergens, Steven H.
supporting information, p. 3065 - 3071 (2017/03/11)
High-throughput screening and lab-scale optimization were combined to develop the catalytic system trans-RuCl2((S,S)-skewphos)((R,R)-dpen), 2-PrONa, and 2-PrOH. This system hydrogenates functionalized α-phenoxy and related amides at room temperature under 4 atm H2 pressure to give chiral alcohols with up to 99% yield and in greater than 99% enantiomeric excess via dynamic kinetic resolution.
A new mechanism of enantioselectivity toward chiral primary alcohol by lipase from Pseudomonas cepacia
Meng, Xiao,Guo, Li,Xu, Gang,Wu, Jian-Ping,Yang, Li-Rong
, p. 109 - 115 (2014/12/11)
The stereo-recognition of chiral primary alcohols by lipase from Pseudomonas cepacia was found to deviate from earlier observations. Enantioselectivity toward 14 pairs of chiral primary alcohol esters by this lipase was dependent on the existence of an Onon-α(oxygen at non-α-position of the acyloxy group) in the alcohol moiety, and decreased as the size of the acyl moiety increased. Chemical modification on the lipase and molecular dynamics simulations indicated that Tyr29located within the catalytic cavity forms a hydrogen bond with the Onon-αof the preferred enantiomer of the primary alcohol ester. However, a larger acyl moiety suffered stronger hindrance from the catalytic cavity wall of the lipase, pushing the Onon-αaway from Tyr29, and thus weakening the stereo-recognition.
CATALYSTS AND PROCESSES FOR THE HYDROGENATION OF AMIDES
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Paragraph 0274; 0275; 0276; 0277; 0278; 0279, (2014/06/24)
There is provided a process for the reduction of one or more amide moieties in a compound comprising contacting the compound with hydrogen gas and a transition metal catalyst in the presence or absence of a base under conditions for the reduction an amide bond. The presently described processes can be performed at low catalyst loading using relatively mild temperature and pressures, and optionally, in the presence or absence of a base or high catalyst loadings using low temperatures and pressures and high loadings of base to effect dynamic kinetic resolution of achiral amides.
Homobenzotetramisole-catalyzed kinetic resolution of α-Aryl-, α-Aryloxy-, and α-Arylthioalkanoic acids
Yang, Xing,Birman, Vladimir B.
supporting information; experimental part, p. 2301 - 2304 (2010/01/19)
Effective kinetic resolutions of α-aryl-, αaryloxy-, and α-arylthioalkanoic acids have been achieved via in situ generation of their symmetrical anhydrides and enantioselective alcoholysis in the presence of homobenzotetramisole (HBTM) 3.
Enantioselective synthesis of chiral β-aryloxy alcohols by asymmetric hydrogenation of a-aryloxy aldehydes via dynamic kinetic resolution
Zhou, Zhang-Tao,Xie, Jian-Hua,Zhou, Qi-Lin
supporting information; experimental part, p. 363 - 366 (2009/11/30)
A catalytic enantioselective hydrogenation of racemic α-aryloxy aldehydes via dynamic kinetic resolution has been developed by using (diamine)(spirodiphosphine)ruthenium(II) chloride [RuCl 2(SDPs)(diamine)] catalysts. Employing this new reactio
Highly enantioselective kinetic resolution of primary alcohols of the type Ph-X-CH(CH3)-CH2OH by Pseudomonas cepacia lipase: Effect of acyl chain length and solvent
Mezzetti, Alessandra,Keith, Curtis,Kazlauskas, Romas J.
, p. 3917 - 3924 (2007/10/03)
Although lipase from Pseudomonas cepacia (PCL) shows high enantioselectivity towards many secondary alcohols, it usually exhibits only low to moderate enantioselectivity towards primary alcohols. To increase this enantioselectivity, we optimised the reaction conditions for the PCL-catalysed hydrolysis of esters of three chiral primary alcohols: 2-methyl-3-phenyl-1- propanol 1, 2-phenoxy-1-propanol 2 and solketal 3. The enantioselectivity towards 1-acetate increased from E=16 to 38 upon changing the solvent from ethyl ether/phosphate buffer to 30% n-propanol in phosphate buffer and increased again to E ≥190 upon changing the substrate from 1-acetate to 1-heptanoate. The same changes increased the enantioselectivity towards alcohol 2 from E=17 to 70, but did not significantly increase the enantioselectivity towards alcohol 3. The best solvent was similar to the solvent used to crystallise the open form of PCL and likely stabilises the open form of PCL. This stabilisation may increase the enantioselectivity by removing kinetic contributions from a non-enantioselective lid-opening step. We determined the kinetic contribution of the lid-opening step by measuring the interfacial activation of PCL. The activation energy for the PCL-catalysed hydrolysis of ethyl acetate was at least 2.6 kcal/mol lower in the presence of a water-organic solvent interface.
Resolution of 2-aryloxy-1-propanols via lipase-catalyzed enantioselective acylation in organic media
Miyazawa, Toshifumi,Yukawa, Tomoyuki,Koshiba, Takashi,Sakamoto, Hiroko,Ueji, Shinichi,Yanagihara, Ryoji,Yamada, Takashi
, p. 1595 - 1602 (2007/10/03)
2-Aryloxy-1-propanols, primary alcohols with an oxygen atom at the stereocenter, were resolved with good to high enantioselectivity by acylation with vinyl butanoate mediated by Pseudomonas sp. lipase in di-iso-propyl ether. Potential factors affecting the enantioselectivity of the enzymatic acylation were examined: solvents, acyl donors and temperature. Using this enantioselective acylation procedure, enantiomerically pure (R)-2-(4-chlorophenoxy)-1-propanol was prepared on a gram scale.
Molecular basis for enantioselectivity of lipase from Pseudomonas cepacia toward primary alcohols. Modeling, kinetics, and chemical modification of Tyr29 to increase or decrease enantioselectivity
Tuomi, W. Victor,Kazlauskas, Romas J.
, p. 2638 - 2647 (2007/10/03)
Lipase from Pseudomonas cepacia (PCL) shows good enantioselectivity toward primary alcohols. An empirical rule can predict which enantiomer of a primary alcohol reacts faster, but there is no reliable strategy to increase the enantioselectivity. We used a combination of molecular modeling of lipase-transition state analogue complexes and kinetic measurements to identify the molecular basis of the enantioselectivity toward two primary alcohols: 2-methyl-3-phenyl-1-propanol, 1, and 2-phenoxy-1-propanol, 2. In hydrolysis of the acetate esters, PCL favors the (S)-enantiomer of both substrates (E = 16 and 17, respectively), but, due to changes in priorities of the substituents, the (S)-enantiomers of 1 and 2 have opposite shapes. Computer modeling of transition state analogues bound to PCL show that primary alcohols bind to PCL differently than secondary alcohols. Modeling and kinetics suggest that the enantioselectivity of PCL toward 1 comes from the binding of the methyl group at the stereocenter within a hydrophobic pocket for the fast-reacting enantiomer, but not for the slow-reacting enantiomer. On the other hand, the enantioselectivity toward 2 comes from an extra hydrogen bond between the phenoxy oxygen of the substrate to the phenolic OH of Tyr29. This hydrogen bond may slow release of the (R)-alcohol and thus account for the reversal of enantioselectvity. To decrease the enantioselectivity of PCL toward 2-acetate by a factor of 2 to E = 8, we eliminated the hydrogen bond by acetylation of the tyrosyl residues with N- acetylimidazole. To increase the enantioselectivity of PCL toward 2-acetate by a factor of 2 to E = 36, we increased the strength of the hydrogen bond by nitration of the tyrosyl residues with tetranitromethane. This is one of the first examples of a rationally designed modification of a lipase to increase enantioselectivity.
