59-47-2Relevant academic research and scientific papers
Ligand-Free Copper-Catalyzed Ullmann-Type C?O Bond Formation in Non-Innocent Deep Eutectic Solvents under Aerobic Conditions
Capriati, Vito,García-álvarez, Joaquín,Marinò, Manuela,Perna, Filippo M.,Quivelli, Andrea Francesca,Vitale, Paola
, (2021/12/09)
An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeded under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [CuI or CuII species] loading up to 5 mol% and K2CO3 as the base, providing the desired aryloxy derivatives in up to 98 % yield. The potential application of the methodology was demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e. g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin, and Chlorphenesin) on a 2 g scale in 70–96 % yield. Catalyst, base, and deep eutectic solvent could easily and successfully be recycled up to seven times with an E-factor as low as 5.76.
Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max
Zhang, Chen,Li, Chuang,Zhu, Xiu-xiu,Liu, You-yi,Zhao, Jun,Wu, Min-chen
, p. 2795 - 2803 (2020/09/01)
A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, αS = 93.7% and βR = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (kcatS/KmS = 2.50 mM?1 s?1) of purified GmEH3 for (S)-5a was slightly higher than that (kcatR/KmR = 1.52 mM?1 s?1) for (R)-5a, whereas the kcat/Km (5.16 mM?1 s?1) for (S)-7a was much higher than that (0.09 mM?1 s?1) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 °C for 1.5 h afforded (R)-5b with 90.2% eep and 95.4% yieldp, while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ees and 43.2% yields. Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.
MnIII Porphyrins: Catalytic Coupling of Epoxides with CO2 under Mild Conditions and Mechanistic Considerations
Milani, Jorge L. S.,Meireles, Alexandre M.,Bezerra, Werberson A.,Martins, Dayse. C. S.,Cangussu, Danielle,das Chagas, Rafael P.
, p. 4393 - 4402 (2019/08/01)
A series of 5,10,15,20-tetrakis(2,3-dichlorophenyl)porphyrinate complexes of manganese(III) [MnIII(T2,3DCPP)X] with six different axial ligands (X=NO3 ?, AcO?, IO3 ?, Br?, Cl?, HO?) were investigated as catalysts in the cycloaddition reactions of CO2 and styrene oxide (SO), under mild conditions, i. e., atmospheric pressure and 60 °C. [MnIIIT(2,3DCPP)IO3] showed the best catalytic performance, selectively producing the respective cyclic carbonate from diverse epoxides using tetrabutylammonium bromide as a nucleophile source. Mechanistic considerations were inferred from electronic spectra and spectrophotometric titrations, showing that there are a series of equilibriums involved in the formation of the catalytic active species. Stability constants for the proposed equilibrium models were determined using SQUAD software. A catalytic cycle has been proposed based on those observations.
Stereoselective Hydrolysis of Epoxides by reVrEH3, a Novel Vigna radiata Epoxide Hydrolase with High Enantioselectivity or High and Complementary Regioselectivity
Hu, Die,Tang, Cunduo,Li, Chuang,Kan, Tingting,Shi, Xiaoling,Feng, Lei,Wu, Minchen
, p. 9861 - 9870 (2017/11/22)
To provide more options for the stereoselective hydrolysis of epoxides, an epoxide hydrolase (VrEH3) gene from Vigna radiata was cloned and expressed in Escherichia coli. Recombinant VrEH3 displayed the maximum activity at pH 7.0 and 45 °C and high stability at pH 4.5-7.5 and 55 °C. Notably, reVrEH3 exhibited high and complementary regioselectivity toward styrene oxides 1a-3a and high enantioselectivity (E = 48.7) toward o-cresyl glycidyl ether 9a. To elucidate these interesting phenomena, the interactions of the three-dimensional structure between VrEH3 and enantiomers of 1a and 9a were analyzed by molecular docking simulation. Using E. coli/vreh3 whole cells, gram-scale preparations of (R)-1b and (R)-9a were performed by enantioconvergent hydrolysis of 100 mM rac-1a and kinetic resolution of 200 mM rac-9a in the buffer-free water system at 25 °C. These afforded (R)-1b with >99% eep and 78.7% overall yield after recrystallization and (R)-9a with >99% ees, 38.7% overall yield, and 12.7 g/L/h space-time yield.
Asymmetric hydrolysis of styrene oxide by PvEH2, a novel Phaseolus vulgaris epoxide hydrolase with extremely high enantioselectivity and regioselectivity
Li, Chuang,Hu, Die,Zong, Xun-Cheng,Deng, Chao,Feng, Lei,Wu, Min-Chen,Li, Jian-Fang
, p. 57 - 61 (2017/09/08)
A novel EH from Phaseolus vulgaris, PvEH2, was discovered based on the computer-aided analysis, and its encoding gene was cloned and expressed in E. coli Rossetta (DE3). The substrate spectrum of recombinant (re) PvEH2 was assayed, among which the enantiomeric ratio of rePvEH2 towards racemic styrene oxide (rac-1a) was > 200, while its regioselectivity coefficients, αS and βR, towards (S)- and (R)-1a were 99.1 and 69.8%, respectively. The asymmetric hydrolysis of 20 mM rac-1a by rePvEH2-expressing whole cells was performed at 25 °C, retaining (R)-1a with > 99.5% ees and 49.4% yield and producing (R)-phenyl-1,2-ethanediol (1b) with 96.2% eep and 49.7% yield in 40 min.
Asymmetric Hydrolytic and Aminolytic Kinetic Resolution of Racemic Epoxides using Recyclable Macrocyclic Chiral Cobalt(III) Salen Complexes
Tak, Rajkumar,Kumar, Manish,Menapara, Tusharkumar,Gupta, Naveen,Kureshy, Rukhsana I.,Khan, Noor-ul H.,Suresh
supporting information, p. 3990 - 4001 (2017/11/22)
New chiral macrocyclic cobalt(III) salen complexes were synthesized and used as catalyst for the asymmetric kinetic resolution (AKR) of terminal epoxides and glycidyl ethers with aromatic/aliphatic amines and water as nucleophiles. This is the first occasion where a Co(III) salen complex demonstrated its ability to catalyze AKR as well as hydrolytic kinetic resolution (HKR) reactions. Excellent enantiomeric excesses of the epoxides, the corresponding amino alcohols and diols (upto 99%) with quantitative yields were achieved by using the chiral Co(III) salen complexes in dichloromethane at room temperature. This protocol was further extended for the synthesis of two important drug molecules, i.e., (S)-propranolol and (R)-naftopidil. The catalytic system was also explored for the synthesis of chirally pure diols and chiral cyclic carbonates using carbon dioxide as a greener renewable C1 source. The catalyst was recycled for upto 5 catalytic cycles with retention of enantioselectivity. (Figure presented.).
A PROPYL-PHENYL-ETHER DERIVATIVE, AND MELANOGENESIS INHIBITOR, SKIN-LIGHTENING AGENT, ANTIMICROBIAL AGENT AND COSMETIC CONTAINING SAID PROPYL-PHENYL-ETHER DERIVATIVE
-
Paragraph 0158-0160, (2016/12/12)
Provided is a compound that exhibits an excellent melanogenesis-inhibiting effect (skin-lightening effect), exhibits an excellent antimicrobial effect, excels in terms of temporal stability and the like, and is suitable for use as an ingredient of a cosmetic. Said compound is a propyl-phenyl-ether derivative compound comprising a propyl group that has a substituent such as a hydroxyl group and is bound to the hydroxyl group of a phenol group that has a substituent such as a tert-butyl group. A melanogenesis inhibitor, skin-lightening agent, and antimicrobial agent containing the aforementioned compound as an active ingredient are also provided, as is a cosmetic characterized by containing said compound.
Three different types of chirality-driven crystallization within the series of uniformly substituted phenyl glycerol ethers
Bredikhin, Alexander A.,Bredikhina, Zemfira A.,Novikova, Victorina G.,Pashagin, Alexander V.,Zakharychev, Dmitry V.,Gubaidullin, Aidar T.
, p. 1092 - 1103 (2015/02/05)
Seven chiral arylglycerol ethers 2-R-C6H4-O-CH2CH(OH)CH2OH (R 5 H, Me, Et, Allyl, n-Pr, i-Pr, tert-Bu) were synthesized in racemic and scalemic form. The IR spectra, melting points, and enthalpies of fusion for racemic and scalemic samples of every species were measured, the entropies of enantiomers mixing in the liquid state and Gibbs free energies of a racemic compound formation were derived and binary phase diagrams were reconstructed for the whole family. Solid racemic compounds stabilities were ranked for the four substances. Spontaneous resolution was established for the registered chiral drug mephenesin and its ethyl analogue. Metastable anomalous conglomerate, forming crystals having three independent R and one independent S molecules in the unit cell, is formed during solution crystallization of tert-butyl derivative; metastable phase transforms slowly into traditional racemic conglomerate. Chirality 20:1092-1103, 2008.
Asymmetric hydrolytic kinetic resolution with recyclable polymeric Co(iii)-salen complexes: A practical strategy in the preparation of (S)-metoprolol, (S)-toliprolol and (S)-alprenolol: Computational rationale for enantioselectivity
Roy, Tamal,Barik, Sunirmal,Kumar, Manish,Kureshy, Rukhsana I.,Ganguly, Bishwajit,Khan, Noor-Ul H.,Abdi, Sayed H. R.,Bajaj, Hari C.
, p. 3899 - 3908 (2015/02/19)
A series of chiral polymeric Co(iii)-salen complexes based on a number of achiral and chiral linkers were synthesized and their catalytic performances were assessed in the asymmetric hydrolytic kinetic resolution of terminal epoxides. The effects of the linker were judiciously studied and it was found that in the case of the chiral BINOL-based polymeric salen complex 1, there was an enrichment in catalyst reactivity and enantioselectivity of the unreacted epoxide, particularly in the case of short as well as long chain aliphatic epoxides. Good isolated yields of the unreacted epoxide (up to 46% compared to 50% theoretical yield) along with high enantioselectivity (up to 99%) were obtained in most cases using catalyst 1. Further studies showed that catalyst 1 could retain its catalytic activity for six cycles under the present reaction conditions without any significant loss in activity or enantioselectivity. To show the practical applicability of the above synthesized catalyst we have synthesised some potent chiral β-blockers in moderate yield and high enantioselectivity using complex 1. The DFT (M06-L/6-31+G??//ONIOM(B3LYP/6-31G?:STO-3G)) calculations revealed that the chiral BINOL linker influences the enantioselectivity achieved with Co(iii)-salen complexes. Further, the transition state calculations show that the R-BINOL linker with the (S,S)-Co(iii)-salen complex is energetically preferred over the corresponding S-BINOL linker with the (S,S)-Co(iii)-salen complex for the HKR of 1,2-epoxyhexane. The role of non-covalent C-H?π interactions and steric effects has been discussed to control the HKR reaction of 1,2-epoxyhexane.
Guaifenesin derivatives promote neurite outgrowth and protect diabetic mice from neuropathy
Hadimani, Mallinath B.,Purohit, Meena K.,Vanampally, Chandrashaker,Van Der Ploeg, Randy,Arballo, Victor,Morrow, Dwane,Frizzi, Katie E.,Calcutt, Nigel A.,Fernyhough, Paul,Kotra, Lakshmi P.
, p. 5071 - 5078 (2013/07/26)
In diabetic patients, an early index of peripheral neuropathy is the slowing of conduction velocity in large myelinated neurons and a lack of understanding of the basic pathogenic mechanisms hindered therapeutics development. Racemic (R/S)-guaifenesin (1) was identified as a potent enhancer of neurite outgrowth using an in vitro screen. Its R-enantiomer (R)-1 carried the most biological activity, whereas the S-enantiomer (S)-1 was inactive. Focused structural variations to (R/S)-1 was conducted to identify potentially essential groups for the neurite outgrowth activity. In vivo therapeutic studies indicated that both (R/S)-1 and (R)-1 partially prevented motor nerve conduction velocity slowing in a mouse model of type 1 diabetes. In vitro microsomal assays suggested that compounds (R)-1 and (S)-1 are not metabolized rapidly, and PAMPA assay indicated moderate permeability through the membrane. Findings revealed here could lead to the development of novel drugs for diabetic neuropathy.
