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.
Asymmetric Transfer Hydrogenation of (Hetero)arylketones with Tethered Rh(III)-N-(p-Tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine Complexes: Scope and Limitations
Zheng, Long-Sheng,Llopis, Quentin,Echeverria, Pierre-Georges,Férard, Charlène,Guillamot, Gérard,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie
, p. 5607 - 5615 (2017/06/07)
A series of new tethered Rh(III)/Cp? complexes containing the N-(p-tolylsulfonyl)-1,2-diphenylethylene-1,2-diamine ligand have been prepared, characterized, and evaluated in the asymmetric transfer hydrogenation (ATH) of a wide range of (hetero)aryl ketones. The reaction was performed under mild conditions with the formic acid/triethylamine (5:2) system as the hydrogen source and provided enantiomerically enriched alcohols with good yields and high to excellent enantioselectivities. Although the nature of the substituents on the phenyl tethering ring did not alter the stereochemical outcome of the reaction, complexes bearing electron-donating groups exhibited a higher catalytic activity than those having electron-withdrawing groups. A scale-up of the ATH of 4-chromanone to the gram scale quantitatively delivered the reduced product with excellent enantioselectivity, demonstrating the potential usefulness of these new complexes.
1-acenaphthenol synthesis and enantiomer separation method
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Paragraph 0014, (2017/08/27)
The invention discloses a 1-acenaphthenol synthesis and enantiomer separation method. The method particularly comprises the following steps that 1-acenaphthenone serves as a raw material, catalytic reduction hydrogenation can be conducted through a catalyst to obtain racemic 1-acenaphthenol, the racemic 1-acenaphthenol is subjected to dynamic kinetic splitting and then separated to obtain an R-1-acenaphthenol acyl compound and S-1-acenaphthenol, the 1-acenaphthenol is subjected to dynamic kinetic splitting, only an R-1-acenaphthenol acyl compound is obtained, the R-1-acenaphthenol acyl compound obtained through kinetic splitting or dynamic kinetic splitting is hydrolyzed, and then R-1-acenaphthenol can be obtained. The method has the advantages of being easy to implement, high in product yield, good in optical purity and the like, and great guidance and application value is achieved in 1-acenaphthenol synthesis and splitting research.
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.
A green route to enantioenriched (S)-arylalkyl carbinols by deracemization via combined lipase alkaline-hydrolysis/Mitsunobu esterification
Houiene, Zahia,Merabet-Khelassi, Mounia,Bouzemi, Nassima,Riant, Olivier,Aribi-Zouioueche, Louisa
, p. 290 - 296 (2013/04/23)
Herein we report results of the chemoenzymatic deracemization of a range of secondary benzylic acetates 1a-9a via a sequence of hydrolysis with CAL-B lipase in non-conventional media, combined with esterification of the recovered alcohol according to the Mitsunobu protocol following an enzymatic kinetic resolution (KR). The KR of racemic acetates 1a-9a via an enzymatic hydrolysis, with CAL-B lipase and Na2CO3, in non-aqueous media was optimized and gave high selectivities (E ? 200) at good conversions (C >49%) for all of the substrates studied. This method competes well with the traditional one performed in a phosphate buffer solution. The deracemization using Mitsunobu inversion gave the (S)-acetates in moderate to excellent enantiomeric excess 75% ee 99%, in acceptable isolated yields 70% yield 89%, and with some variations according to the acetate structure.
Green methodology for enzymatic hydrolysis of acetates in non-aqueous media via carbonate salts
Merabet-Khelassi, Mounia,Houiene, Zahia,Aribi-Zouioueche, Louisa,Riant, Olivier
experimental part, p. 828 - 833 (2012/09/25)
Herein we report a new approach to enantiomerically enriched acetates using a lipase-catalyzed hydrolysis in non-aqueous media by alkaline carbonate salts. The use of sodium carbonate in the enzymatic hydrolysis with Candida antarctica lipase B (CAL-B) of racemic acetates shows a large enhancement of the reactivity and selectivity of this lipase. The role of the carbonate salts, the amount and the nature of the alkaline earth metal on the efficiency of this new pathway are investigated. The enzymatic kinetic resolution of acetates 1a-9a, by enzymatic-carbonate hydrolysis under mild conditions is described. In all cases, the resulting alcohols and remaining acetates were obtained in high ee values (up to >99%) while the selectivities reached E >500.
Enantioselective hydrosilylation of aromatic alkenes catalyzed by chiral bis(oxazolinyl)phenyl-rhodium acetate complexes
Naito, Tatsuo,Yoneda, Takuma,Ito, Jun-Ichi,Nishiyama, Hisao
, p. 2957 - 2960 (2013/02/22)
Highly efficient and enantioselective hydrosilylation of aromatic alkenes catalyzed by the chiral rhodium acetate complexes with the bis(oxazolinyl)phenyl ligands has been reported that afforded chiral silane derivatives with up to 99% ee. Georg Thieme Ve
Solution-phase synthesis and evaluation of tetraproline chiral stationary phases
Dai, Zhi,Ye, Guozhong,Pittman Jr., Charles U.,Li, Tingyu
experimental part, p. 329 - 338 (2012/05/20)
A protocol was developed for the solution-phase synthesis of multigram amounts of two 9-fluorenylmethoxycarbonyl (Fmoc)-protected tetraproline peptides. These tetraproline peptides were then attached to amino derivatized silica gel. The replacement of the Fmoc group with the trimethylacetyl group lead to two tetraproline chiral stationary phases (CSPs). A comparison of the chromatographic behavior of these two solution-phase-synthesized tetraproline CSPs with that prepared by stepwise solid-phase synthesis revealed that all three had similar chromatographic performance for resolving 53 model analytes. This suggests that the solution-phase synthesis of oligoprolines, which allows for the specific benefits of good batch reproducibility, selector homogeneity, and possibly low cost, is a feasible alternative to the solid-phase synthesis of oligoproline CSPs. Copyright
Silylation-based kinetic resolution of monofunctional secondary alcohols
Sheppard, Cody I.,Taylor, Jessica L.,Wiskur, Sheryl L.
supporting information; experimental part, p. 3794 - 3797 (2011/10/02)
The nucleophilic small molecule catalyst (-)-tetramisole was found to catalyze the kinetic resolution of monofunctional secondary alcohols via enantioselective silylation. Optimization of this new methodology allows for selectivity factors up to 25 utilizing commercially available reagents and mild reaction conditions.
