The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Shaohua Huang - One of the best experts on this subject based on the ideXlab platform.
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synthesis of novel chiral imidazolium stationary phases and their enantioseparation evaluation by high performance liquid chromatography
Analytica Chimica Acta, 2016Co-Authors: Tao Wang, Haiyan Yang, Shaohua HuangAbstract:Two novel chiral stationary phases (CSPs) were prepared by bonding chiral imidazoliums on the surface of silica gel. The chiral imidazoles were derivatized from chiral amines, 1-phenylethylamine and 1-(1-naphthyl)ethylamine. The obtained CSPs were characterized by Fourier Transform Infrared (FT-IR) spectroscopy and elemental analysis (EA), demonstrating the bonding densities of CSP 1 and CSP 2 were 0.43 mmol g−1 and 0.40 mmol g−1, respectively. These two CSPs could be used to availably separate 8 pharmaceuticals, 7 mandelic acid/its derivatives, 2 1-phenylethylamine derivatives, 1 1,1′-bi-2-naphthol, and 1 camphorsulfonic acid in high-performance liquid chromatography (HPLC). It is found that CSP 1 could effectively enantioseparate most chiral analytes, especially the acidic components, while CSP 2 could enantiorecognize all chiral analytes, although a number of components did not achieve baseline separation. Additionally, the effects of mobile phase composition, mobile phase pH and salt content, chiral selector structures, and analyte structures on the enantiorecognitions of the two CSPs were investigated. It is found that high acetonitrile content in mobile phases was conducive to enantiorecognition. Mobile phase pH and salt content could alter the retention behaviors of different enantiomers of the same chiral compound, resulting in better enantioresolution. Moreover, both chiral selector structures and substituted groups of analytes played a significant role in the separation of chiral solutes.
Magnus Carlquist - One of the best experts on this subject based on the ideXlab platform.
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improvement of whole cell transamination with saccharomyces cerevisiae using metabolic engineering and cell pre adaptation
Microbial Cell Factories, 2017Co-Authors: Nora Weber, Mariefrancoise Gorwagrauslund, Magnus CarlquistAbstract:Whole-cell biocatalysis based on metabolically active baker’s yeast with engineered transamination activity can be used to generate molecules carrying a chiral amine moiety. A prerequisite is though to express efficient ω-transaminases and to reach sufficient intracellular precursor levels. Herein, the efficiency of three different ω-transaminases originating from Capsicum chinense, Chromobacterium violaceum, and Ochrobactrum anthropi was compared for whole-cell catalyzed kinetic resolution of racemic 1-phenylethylamine to (R)-1-phenylethylamine. The gene from the most promising candidate, C. violaceum ω-transaminase (CV-TA), was expressed in a strain lacking pyruvate decarboxylase activity, which thereby accumulate the co-substrate pyruvate during glucose assimilation. However, the conversion increased only slightly under the applied reaction conditions. In parallel, the effect of increasing the intracellular pyridoxal-5′-phosphate (PLP) level by omission of thiamine during cultivation was investigated. It was found that without thiamine, PLP supplementation was redundant to keep high in vivo transamination activity. Furthermore, higher reaction rates were achieved using a strain containing several copies of CV-TA gene, highlighting the necessity to also increase the intracellular transaminase level. At last, this strain was also investigated for asymmetric whole-cell bioconversion of acetophenone to (S)-1-phenylethylamine using l-alanine as amine donor. Although functionality could be demonstrated, the activity was extremely low indicating that the native co-product removal system was unable to drive the reaction towards the amine under the applied reaction conditions. Altogether, our results demonstrate that (R)-1-phenylethylamine with >99% ee can be obtained via kinetic resolution at concentrations above 25 mM racemic substrate with glucose as sole co-substrate when combining appropriate genetic and process engineering approaches. Furthermore, the engineered yeast strain with highest transaminase activity was also shown to be operational as whole-cell catalyst for the production of (S)-1-phenylethylamine via asymmetric transamination of acetophenone, albeit with very low conversion.
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Improvement of whole-cell transamination with Saccharomyces cerevisiae using metabolic engineering and cell pre-adaptation
Microbial Cell Factories, 2017Co-Authors: Nora Weber, Marie Gorwa-grauslund, Magnus CarlquistAbstract:Background Whole-cell biocatalysis based on metabolically active baker’s yeast with engineered transamination activity can be used to generate molecules carrying a chiral amine moiety. A prerequisite is though to express efficient ω -transaminases and to reach sufficient intracellular precursor levels. Results Herein, the efficiency of three different ω -transaminases originating from Capsicum chinense , Chromobacterium violaceum , and Ochrobactrum anthropi was compared for whole-cell catalyzed kinetic resolution of racemic 1-phenylethylamine to ( R )-1-phenylethylamine. The gene from the most promising candidate, C . violaceum ω -transaminase (CV-TA), was expressed in a strain lacking pyruvate decarboxylase activity, which thereby accumulate the co-substrate pyruvate during glucose assimilation. However, the conversion increased only slightly under the applied reaction conditions. In parallel, the effect of increasing the intracellular pyridoxal-5′-phosphate (PLP) level by omission of thiamine during cultivation was investigated. It was found that without thiamine, PLP supplementation was redundant to keep high in vivo transamination activity. Furthermore, higher reaction rates were achieved using a strain containing several copies of CV-TA gene, highlighting the necessity to also increase the intracellular transaminase level. At last, this strain was also investigated for asymmetric whole-cell bioconversion of acetophenone to ( S )-1-phenylethylamine using l -alanine as amine donor. Although functionality could be demonstrated, the activity was extremely low indicating that the native co-product removal system was unable to drive the reaction towards the amine under the applied reaction conditions. Conclusions Altogether, our results demonstrate that ( R )-1-phenylethylamine with >99% ee can be obtained via kinetic resolution at concentrations above 25 mM racemic substrate with glucose as sole co-substrate when combining appropriate genetic and process engineering approaches. Furthermore, the engineered yeast strain with highest transaminase activity was also shown to be operational as whole-cell catalyst for the production of ( S )-1-phenylethylamine via asymmetric transamination of acetophenone, albeit with very low conversion.
Otto Dopfer - One of the best experts on this subject based on the ideXlab platform.
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effects of aromatic fluorine substitution on protonated neurotransmitters the case of 2 phenylethylamine
Chemistry: A European Journal, 2016Co-Authors: Markus Schutz, Aude Bouchet, Barbara Chiavarino, Maria Elisa Crestoni, Simonetta Fornarini, Otto DopferAbstract:Fluorination of pharmaceutical compounds is a common tool to modulate their physiochemical properties. We determine the effects of site-specific aromatic fluorine substitution on the geometric, energetic, vibrational, and electronic properties of the protonated neurotransmitter 2-Phenylethylamine (xF-H(+) PEA, x=ortho, meta, para) by infrared multiphoton photodissociation (IRMPD) in the fingerprint range (600-1750 cm(-1) ) and quantum chemical calculations at the B3LYP-D3/aug-cc-pVTZ level. The IRMPD spectra of all ions are assigned to their folded gauche conformers stabilized by intramolecular NH(+) ⋅⋅⋅π hydrogen bonds (H-bonds) between the protonated amino group and the aromatic ring. H→F substitution reduces the symmetry and allows for additional NH(+) ⋅⋅⋅F interactions in oF-H(+) PEA, leading to three distinct gauche conformers. In comparison to oF-H(+) PEA, the fluorination effects on the energy landscape (energy ordering and isomerization barriers) in pF-H(+) PEA and mF-H(+) PEA with one and two gauche conformers are less pronounced. The strengths of the intramolecular NH(+) ⋅⋅⋅F and NH(+) ⋅⋅⋅π bonds are analyzed by the noncovalent interaction (NCI) method.
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ir spectrum of the protonated neurotransmitter 2 phenylethylamine dispersion and anharmonicity of the nh3 π interaction
Physical Chemistry Chemical Physics, 2015Co-Authors: Aude Bouchet, Markus Schutz, Barbara Chiavarino, Maria Elisa Crestoni, Simonetta Fornarini, Otto DopferAbstract:The structure and dynamics of the highly flexible side chain of (protonated) phenylethylamino neurotransmitters are essential for their function. The geometric, vibrational, and energetic properties of the protonated neutrotransmitter 2-Phenylethylamine (H+PEA) are characterized in the N–H stretch range by infrared photodissociation (IRPD) spectroscopy of cold ions using rare gas tagging (Rg = Ne and Ar) and anharmonic calculations at the B3LYP-D3/(aug-)cc-pVTZ level including dispersion corrections. A single folded gauche conformer (G) protonated at the basic amino group and stabilized by an intramolecular NH+–π interaction is observed. The dispersion-corrected density functional theory calculations reveal the important effects of dispersion on the cation–π interaction and the large vibrational anharmonicity of the NH3+ group involved in the NH+–π hydrogen bond. They allow for assigning overtone and combination bands and explain anomalous intensities observed in previous IR multiple-photon dissociation spectra. Comparison with neutral PEA reveals the large effects of protonation on the geometric and electronic structure.
Tao Wang - One of the best experts on this subject based on the ideXlab platform.
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synthesis of novel chiral imidazolium stationary phases and their enantioseparation evaluation by high performance liquid chromatography
Analytica Chimica Acta, 2016Co-Authors: Tao Wang, Haiyan Yang, Shaohua HuangAbstract:Two novel chiral stationary phases (CSPs) were prepared by bonding chiral imidazoliums on the surface of silica gel. The chiral imidazoles were derivatized from chiral amines, 1-phenylethylamine and 1-(1-naphthyl)ethylamine. The obtained CSPs were characterized by Fourier Transform Infrared (FT-IR) spectroscopy and elemental analysis (EA), demonstrating the bonding densities of CSP 1 and CSP 2 were 0.43 mmol g−1 and 0.40 mmol g−1, respectively. These two CSPs could be used to availably separate 8 pharmaceuticals, 7 mandelic acid/its derivatives, 2 1-phenylethylamine derivatives, 1 1,1′-bi-2-naphthol, and 1 camphorsulfonic acid in high-performance liquid chromatography (HPLC). It is found that CSP 1 could effectively enantioseparate most chiral analytes, especially the acidic components, while CSP 2 could enantiorecognize all chiral analytes, although a number of components did not achieve baseline separation. Additionally, the effects of mobile phase composition, mobile phase pH and salt content, chiral selector structures, and analyte structures on the enantiorecognitions of the two CSPs were investigated. It is found that high acetonitrile content in mobile phases was conducive to enantiorecognition. Mobile phase pH and salt content could alter the retention behaviors of different enantiomers of the same chiral compound, resulting in better enantioresolution. Moreover, both chiral selector structures and substituted groups of analytes played a significant role in the separation of chiral solutes.
Franz Baumberger - One of the best experts on this subject based on the ideXlab platform.
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4-aryl-substituted 2,5-dimethoxyphenethylamines: synthesis and serotonin 5-HT(2A) receptor affinities
2015Co-Authors: Daniel Trachsel, David E Nichols, Stephanie Kidd, Marcel Hadorn, Franz BaumbergerAbstract:A series of novel ligands for the serotonin 5-HT2A/C receptor subtype bearing the 2-Phenylethylamine pharmacophore was synthesized and assayed for its 5-HT2A receptor binding affinity. As the 4’-aryl-substituted 2-(2,5-dimethoxyphenyl)ethylamines were previously unknown, an initial series of twelve compounds was chosen to obtain initial insight into their structure–activity relationships. The 4’-aryl moiety was introduced in moderate-to-high yield by a Pd-catalyzed Suzuki reaction of twelve arylboronic acids with N-Boc-protected 2-(2,5-dimethoxy-4-iodophenyl)ethylamine (8). N-Boc Deprotection then afforded the novel 2-Phenylethylamines 5a–5l. Additionally, biphenyl compound 6 lacking the 5’-MeO substituent was prepared, starting from 2-methoxy-4-hydroxybenzaldehyde. Except for 5l, all of the compounds proved to be antagonists with generally low affinity at the rat 5-HT2A receptor. Substituents are generally not well tolerated on the 4’-aryl moiety, except in the 4’’-position. Indeed, the relatively high affinity of the 4’’-butyl-, 4’’-phenyl-, and 4’-naphthyl-substituted compounds 5i, 5k, and 5e, respectively (Ki32, 33, and 41nm, resp.), attests a rather remarkable tolerance for bulk in this location. Introduction. – The serotonin 5-HT2 receptor family was first identified in 1979 [1]. It is involved in regulation of the cardiovascular system and numerous central processes such as sleep, appetite, and sexual activity. A wide array of mental disorders includin
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4 aryl substituted 2 5 dimethoxyphenethylamines synthesis and serotonin 5 ht2a receptor affinities
Chemistry & Biodiversity, 2009Co-Authors: Daniel Trachsel, David E Nichols, Stephanie Kidd, Marcel Hadorn, Franz BaumbergerAbstract:A series of novel ligands for the serotonin 5-HT(2A/C) receptor subtype bearing the 2-Phenylethylamine pharmacophore was synthesized and assayed for its 5-HT(2A) receptor binding affinity. As the 4'-aryl-substituted 2-(2,5-dimethoxyphenyl)ethylamines were previously unknown, an initial series of twelve compounds was chosen to obtain initial insight into their structure-activity relationships. The 4'-aryl moiety was introduced in moderate-to-high yield by a Pd-catalyzed Suzuki reaction of twelve arylboronic acids with N-Boc-protected 2-(2,5-dimethoxy-4-iodophenyl)ethylamine (8). N-Boc Deprotection then afforded the novel 2-Phenylethylamines 5a-5l. Additionally, biphenyl compound 6 lacking the 5'-MeO substituent was prepared, starting from 2-methoxy-4-hydroxybenzaldehyde. Except for 5l, all of the compounds proved to be antagonists with generally low affinity at the rat 5-HT(2A) receptor. Substituents are generally not well tolerated on the 4'-aryl moiety, except in the 4''-position. Indeed, the relatively high affinity of the 4''-butyl-, 4''-phenyl-, and 4'-naphthyl-substituted compounds 5i, 5k, and 5e, respectively (K(i)=32, 33, and 41nM, resp.), attests a rather remarkable tolerance for bulk in this location.