433-97-6Relevant articles and documents
Substrate docking algorithms and prediction of the substrate specificity of cytochrome P450(cam) and its L244A mutant
De Voss, James J.,Sibbesen, Ole,Zhang, Zhoupeng,Ortiz De Montellano, Paul R.
, p. 5489 - 5498 (1997)
The substrate specificity of cytochrome P450, defined as the ability of a compound to promote NAD(P)H and O2 utilization in the production of either organic or reduced oxygen metabolites, is largely determined by steric and hydrophobic interactions. P450 specificity may therefore be determined by the 'fit' of a compound within the active site. A receptor-constrained three- dimensional screening program (DOCK) has been used to select 11 compounds predicted to fit within the P450(cam) active site and 5 compounds predicted to fit within the L244A P450(cam) but not wild-type active site. The 16 compounds were evaluated as P450(cam) substrates by measuring (a) binding to the enzyme, (b) stimulation of NADH and O2 consumption, (c) enhancement of H2O2 production, and (d) formation of organic metabolites. Seven of the compounds predicted to fit in the active site, and none of the compounds predicted not to fit, were found to be substrates. Compounds predicted to fit very tightly within the active site were poor or non-substrates. The L244A P450(cam) mutant was constructed, expressed, purified, and shown to readily oxidize some of the larger compounds incorrectly predicted to be substrates for the wild-type enzyme. The 5 ligands selected to fit the L244A but not wild-type sites were not detectable substrates, presumably because they fit too tightly into the active site. Retroactive adjustments of the docking program based on an analysis of the docking parameters, particularly variation of the minimum distance allowed between ligand and protein atoms, allow correct predictions for the activity of 15 of the 16 compounds with wild-type P450(cam). The DOCK predictions for the L244A mutant were also improved by changing the minimum contact distances to disfavor the larger compounds. The results indicate that ligands that fill the active site are marginal or non-substrates. A degree of freedom of motion is required for substrate positioning and catalytic function. If parameters are chosen to allow for this requirement, P450(cam) substrate predictions based on ligand docking in the active site can be reasonably accurate.
Aerobic oxidation of aldehydes to carboxylic acids catalyzed by recyclable ag/c3 n4 catalyst
Wu, Chaolong,Yao, Xiaoquan,Yu, Min,Zhou, Li,Zhu, Li
, p. 167 - 175 (2021/03/19)
The oxidation of aldehydes is an efficient methodology for the synthesis of carboxylic acids. Herein we hope to report a simple, efficient and recyclable protocol for aerobic oxidation of aldehydes to carboxylic acid by using C3N4 supported silver nanoparticles (Ag/C3N4) as a catalyst in aqueous solution under mild conditions. Under standard conditions, the corresponding carboxylic acids can be obtained in good to excellent yields. In addition, Ag/C3N4 is convenient for recovery and could be reused three times with satisfactory yields.
Continuous Platform to Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor
Tsukanov, Sergey V.,Johnson, Martin D.,May, Scott A.,Kolis, Stanley P.,Yates, Matthew H.,Johnston, Jeffrey N.
, p. 971 - 977 (2018/08/28)
The synthetic utility of the aza-Henry reaction can be diminished on scale by potential hazards associated with the use of peracid to prepare nitroalkane substrates and the nitroalkanes themselves. In response, a continuous and scalable chemistry platform to prepare aliphatic nitroalkanes on-demand using the oxidation of oximes with peracetic acid and direct reaction of the nitroalkane intermediate in an aza-Henry reaction is reported. A uniquely designed pipes-in-series plug-flow tube reactor addresses a range of process challenges, including stability and safe handling of peroxides and nitroalkanes. The subsequent continuous extraction generates a solution of purified nitroalkane, which can be directly used in the following enantioselective aza-Henry chemistry to furnish valuable chiral diamine precursors with high selectivity, thus completely avoiding isolation of the potentially unsafe low-molecular-weight nitroalkane intermediate. A continuous campaign (16 h) established that these conditions were effective in processing 100 g of the oxime and furnishing 1.4 L of nitroalkane solution.
Copper-Promoted Conversion of Aromatic Amines into Trifluoromethylated Arenes: One-Pot Sandmeyer Trifluoromethylation
Hong, Jianquan,Wang, Guifu,Huo, Lianguang,Zheng, Changge
supporting information, p. 1761 - 1767 (2017/09/06)
A simple copper-promoted one-pot Sandmeyer trifluoromethylation of aromatic amines with Langlois’ reagent has been demonstrated. The reaction is performed in mild reaction conditions under an air atmosphere with good substrate scope and functional group compatibility. It provides an alternative and straightforward synthetic approach to access a variety of trifluoromethylated arenes.