61912-03-6Relevant articles and documents
CO2-Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**
Juhl, Martin,Petersen, Allan R.,Lee, Ji-Woong
supporting information, p. 228 - 232 (2020/11/30)
Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2-mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani–Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO2.
Highly chemoselective and efficient Strecker reaction of aldehydes with TMSCN catalyzed by MgI2 etherate under solvent-free conditions
He, Kailun,Liu, Huijun,Zhang, Xingxian,Zhou, Jing
supporting information, p. 933 - 936 (2019/03/08)
Strecker reaction of various substituted aromatic aldehydes, heteroaromatic aldehydes, aliphatic aldehydes and α,β-unsaturated aldehydes with trimethylsilyl cyanide (TMSCN) was realized in the presence of 5 mol % of MgI2 etherate in a mild, efficient and highly chemoselective manner under solvent-free conditions.
Immobilized Baliospermum montanum hydroxynitrile lyase catalyzed synthesis of chiral cyanohydrins
Jangir, Nisha,Padhi, Santosh Kumar
, p. 32 - 40 (2018/11/27)
Hydroxynitrile lyase (HNL) catalyzed enantioselective C–C bond formation is an efficient approach to synthesize chiral cyanohydrins which are important building blocks in the synthesis of a number of fine chemicals, agrochemicals and pharmaceuticals. Immobilization of HNL is known to provide robustness, reusability and in some cases also enhances activity and selectivity. We optimized the preparation of immobilization of Baliospermium montanum HNL (BmHNL) by cross linking enzyme aggregate (CLEA) method and characterized it by SEM. Optimization of biocatalytic parameters was performed to obtain highest % conversion and ee of (S)-mandelonitrile from benzaldehyde using CLEA-BmHNL. The optimized reaction parameters were: 20 min of reaction time, 7 U of CLEA-BmHNL, 1.2 mM substrate, and 300 mM citrate buffer pH 4.2, that synthesized (S)-mandelonitrile in ～99% ee and ～60% conversion. Addition of organic solvent in CLEA-BmHNL biocatalysis did not improve in % ee or conversion of product unlike other CLEA-HNLs. CLEA-BmHNL could be successfully reused for eight consecutive cycles without loss of conversion or product formation and five cycles with a little loss in enantioselectivity. Eleven different chiral cyanohydrins were synthesized under optimal biocatalytic conditions in up to 99% ee and 59% conversion, however the % conversion and ee varied for different products. CLEA-BmHNL has improved the enantioselectivity of (S)-mandelonitrile synthesis compared to the use of purified BmHNL. Nine aldehydes not tested earlier with BmHNL were converted into their corresponding (S)-cyanohydrins for the first time using CLEA-BmHNL. Among the eleven (S)-cyanohydrins syntheses reported here, eight of them have not been synthesized by any CLEA-HNL. Overall, this study showed preparation, characterization of a stable, robust and recyclable biocatalyst i.e. CLEA-BmHNL and its biocatalytic application in the synthesis of different (S)-aromatic cyanohydrins.
Design, synthesis, and in vitro evaluation of epigoitrin derivatives as neuraminidase inhibitors
Meng, Fanli,Yin, Yan,Lu, Cheng,Duan, Yongbin,Zhu, Yaohua,Huang, Chen,Zhou, Yiming,Xu, Xu,Wu, Fanhong
, p. 2037 - 2046 (2018/09/06)
Abstract: Influenza is an infectious disease which results in numerous epidemics every year. At present, neuraminidase is regarded, as the key therapeutic target against influenza and several well-known neuraminidase inhibitors are widely used as anti-influenza drugs. Combined computational methods including 3D-QSAR and molecular docking were applied to explore the structural–activity relationship with Xu’s compounds as the data set. Ten epigoitrin derivatives were then designed based on the computational results and they displayed 11.1–85.5?μM inhibitory potencies against neuraminidase in the in vitro biological evaluation. The combined computational studies did not only present the structural–activity relationship of Xu’s inhibitors, but also guide the designation of epigoitrin derivatives as novel neuraminidase inhibitors. Graphical abstract: [Figure not available: see fulltext.].
Aminoalcohol neuraminidase inhibitors, and preparation method thereof
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Paragraph 0031; 0035, (2017/09/01)
The invention discloses aminoalcohol neuraminidase inhibitors, and a preparation method thereof. The method concretely comprises the following steps: 1, reacting cinnamaldehyde, lithium perchlorate LiClO4.3H2O and trimethylsilyl cyanide (TMSCN) to obtain cyan analog; 2, reducing the cyan analog under the action of a reducing agent and an additive in order to obtain hydroxyl-substituted amino compounds; 3, reacting the hydroxyl-substituted amino compounds with acyl chloride under an alkaline condition to obtain one neuraminidase inhibitor; and 4, reacting the hydroxyl-substituted amino compounds with substituted benzyl bromide under an alkaline condition to obtain another one neuraminidase inhibitor with another structure. The compounds synthesized in the invention have novel structures, and have good neuraminidase activity.
Acceptorless and Base-free Dehydrogenation of Cyanohydrin with (η6-Arene)halide(Bidentate Phosphine)ruthenium(II) Complex
Kim, Kicheol,Moeljadi, Adhitya Mangala Putra,Hirao, Hajime,Hong, Soon Hyeok
supporting information, p. 3292 - 3298 (2017/09/06)
Ruthenium-catalyzed dehydrogenation of cyanohydrins under acceptorless and base-free conditions was demonstrated for the first time in the synthesis of acyl cyanide. As opposed to the thermodynamically preferred elimination of hydrogen cyanide, the dehydrogenation of cyanohydrins could be kinetically controlled with ruthenium (II) bidentate phosphine complexes. The effects of the arene, phosphine ligands and counter anions were investigated in regard to catalytic activity and selectivity. Selective dehydrogenation can occur via β-hydride elimination with the experimentally observed [(alkoxide)Ru] complex. (Figure presented.).
Fast microwave-assisted resolution of (±)-cyanohydrins promoted by lipase from Candida antarctica
Ribeiro, Sandra S.,Ferreira, Irlon M.,Lima, Jo?o P. F.,De Sousa, Bruno A.,Carmona, Rafaela C.,Santos, Alcindo A. Dos,Porto, André L. M.
, p. 1344 - 1350 (2015/07/15)
Enzymatic kinetic resolution (EKR) of (±)-cyanohydrins was performed by using immobilized lipase from Candida antarctica (CALB) under conventional ordinary conditions (orbital shaking) and under microwave radiation (MW). The use of microwave radiation contributed very expressively on the reduction of the reaction time from 24 to 2 h. Most importantly, high selectivity (up to 92percent eep) as well as conversion was achieved under MW radiation (50-56percent).
A magnetic nanoparticle catalyzed eco-friendly synthesis of cyanohydrins in a deep eutectic solvent
Azizi, Najmedin,Rahimi, Zahra,Alipour, Masoumeh
, p. 61191 - 61198 (2015/07/28)
Magnetic Fe3O4 nanoparticles in deep eutectic solvents (DESs) have been regard as excellent catalysts for highly efficient cyanosilylation of various aldehydes and epoxides using trimethylsilyl cyanide TMSCN in high yields with excellent selectivity. Fe3O4 nanoparticles were synthesized and applied as a catalyst for the preparation of a wide variety of cyanohydrins (α-hydroxy nitriles and β-hydroxy nitriles) in readily available urea-choline chloride deep eutectic solvent DES as the most promising environmentally benign and cost-effective green solvent. Magnetic DES operates at very mild reaction conditions and can be easily recycled without significant loss of its catalytic activity.
Mechanism-Based inactivation of human cytochrome p450 3A4 by two piperazine-Containing compounds
Bolles, Amanda K.,Fujiwara, Rina,Briggs, Erran D.,Nomeir, Amin A.,Furge, Laura Lowe
, p. 1471 - 1475 (2014/12/11)
Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of more than half of pharmaceutic drugs, and inactivation of CYP3A4 can lead to adverse drug-drug interactions. The substituted imidazole compounds 5-fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl) methyl]-1-piperazinyl]pyrimidine (SCH 66712) and 1-[(2-ethyl-4-methyl-1H-imidazol-5-yl)methyl]-4-[4-(trifluoromethyl)-2-pyridinyl]piperazine (EMTPP) have been previously identified as mechanism-based inactivators (MBI) of CYP2D6. The present study shows that both SCH 66712 and EMTPP are also MBIs of CYP3A4. Inhibition of CYP3A4 by SCH 66712 and EMTPP was determined to be con-centration, time, and NADPH dependent. In addition, inactivation of CYP3A4 by SCH 66712 was shown to be unaffected by the presence of electrophile scavengers. SCH 66712 displays type I binding to CYP3A4 with a spectral binding constant (Ks) of 42.9 ± 2.9 μM. The partition ratios for SCH 66712 and EMTPP were 11 and 94, respectively. Whole protein mass spectrum analysis revealed 1:1 binding stoichiometry of SCH 66712 and EMTPP to CYP3A4 and a mass increase consistent with adduction by the inactivators without addition of oxygen. Heme adduction was not apparent. Multiple monooxygenation products with each inactivator were observed; no other products were apparent. These are the first MBIs to be shown to be potent inactivators of both CYP2D6 and CYP3A4.
The combi-CLEA approach: Enzymatic cascade synthesis of enantiomerically pure (S)-mandelic acid
Chmura, Andrzej,Rustler, Sven,Paravidino, Monica,Van Rantwijk, Fred,Stolz, Andreas,Sheldon, Roger A.
, p. 1225 - 1232 (2013/10/22)
Enantiomerically pure (S)-mandelic acid was synthesised from benzaldehyde by sequential hydrocyanation and hydrolysis in a bienzymatic cascade at starting concentrations up to 0.25 M. A cross-linked enzyme aggregate (CLEA) composed of the (S)-selective oxynitrilase from Manihot esculenta and the non-selective nitrilase from Pseudomonas fluorescens EBC 191 was employed as the biocatalyst. The nitrilase produces approx. equal amounts of (S)-mandelic acid and (S)-mandelic amide from (S)-mandelonitrile under standard conditions, but we surprisingly found that high (up to 0.5 M) concentrations of HCN induced a marked drift towards amide production. By including the amidase from Rhodococcus erythopolis in the CLEA we obtained (S)-mandelic acid as the sole product in 90% yield and >99% enantiomeric purity.
