121961-98-6Relevant articles and documents
Silylative Kinetic Resolution of Racemic 1-Indanol Derivatives Catalyzed by Chiral Guanidine
Yoshimatsu, Shuhei,Yamada, Akira,Nakata, Kenya
, p. 452 - 458 (2018/02/19)
Efficient kinetic resolution of racemic 1-indanol derivatives was achieved using triphenylchlorosilane by asymmetric silylation in the presence of chiral guanidine catalysts. The chiral guanidine catalyst (R,R)-N-(1-(β-naphthyl)ethyl)benzoguanidine was found to be highly efficient as only 0.5 mol % catalyst loading was sufficient to catalyze the reaction of various substrates with appropriate conversion and high s-values (up to 89). This catalyst system was successfully applied to the gram-scale silylative kinetic resolution of racemic 1-indanol with high selectivity.
The Oxidation of Hydrophobic Aromatic Substrates by Using a Variant of the P450 Monooxygenase CYP101B1
Sarkar, Md. Raihan,Lee, Joel H. Z.,Bell, Stephen G.
, p. 2119 - 2128 (2017/10/12)
The cytochrome P450 monooxygenase CYP101B1, from a Novosphingobium bacterium is able to bind and oxidise aromatic substrates but at a lower activity and efficiency than norisoprenoids and monoterpenoid esters. Histidine 85 of CYP101B1 aligns with tyrosine 96 of CYP101A1, which, in the latter enzyme forms the only hydrophilic interaction with its substrate, camphor. The histidine residue of CYP101B1 was mutated to phenylalanine with the aim of improving the activity of the enzyme for hydrophobic substrates. The H85F mutant lowered the binding affinity and activity of the enzyme for β-ionone and altered the oxidation selectivity. This variant also showed enhanced affinity and activity towards alkylbenzenes, styrenes and methylnaphthalenes. For example the rate of product formation for acenaphthene oxidation was improved sixfold to 245 nmol per nmol CYP per min. Certain disubstituted naphthalenes and substrates, such as phenylcyclohexane and biphenyls, were oxidised with lower activity by the H85F variant. Variants at H85 (A and G) designed to introduce additional space into the active site so as to accommodate these larger substrates did not improve the oxidation activity. As the H85F mutant of CYP101B1 improved the oxidation of hydrophobic substrates, this residue is likely to be in the substrate binding pocket or the access channel of the enzyme. The side chain of the histidine might interact with the carbonyl groups of the favoured norisoprenoid substrates of CYP101B1.
Conventional chiralpak ID vs. capillary chiralpak ID-3 amylose tris-(3-chlorophenylcarbamate)-based chiral stationary phase columns for the enantioselective HPLC separation of pharmaceutical racemates
Ahmed, Marwa,Gwairgi, Marina,Ghanem, Ashraf
, p. 677 - 682 (2015/03/31)
A comparative enantioselective analysis using immobilized amylose tris-(3-chlorophenylcarbamate) as chiral stationary phase in conventional high-performance liquid chromatography (HPLC) with Chiralpak ID (4.6mm ID×250mm, 5μm silica gel) and micro-HPLC with Chiralpak ID-3 (0.30mm ID×150mm, 3μm silica gel) was conducted. Pharmaceutical racemates of 12 pharmacological classes, namely, α- and β-blockers, anti-inflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs were screened under normal phase conditions. The effect of an organic modifier on the analyte retentions and enantiomer recognition was investigated. Baseline separation was achieved for 1-acenaphthenol, carprofen, celiprolol, cizolirtine carbinol, miconazole, tebuconazole, 4-hydroxy-3-methoxymandelic acid, 1-indanol, 1-(2-chlorophenyl)ethanol, 1-phenyl-2-propanol, flavanone, 6-hydroxyflavanone, 4-bromogluthethimide, and pentobarbital on the 4.6mm ID packed with a 5μm silica column using conventional HPLC. Nonetheless, baseline separation was achieved for aminoglutethimide, naftopidil, and thalidomide on the 0.3mm ID packed with a 3μm silica capillary column. Chirality 26:677-682, 2014.
