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Molecules (Basel, Switzerland) Apr 2019In this paper, the microwave (MW)-assisted catalyst-free and mostly solvent-free Kabachnik-Fields reaction of amino alcohols, paraformaldehyde, and various >P(O)H...
In this paper, the microwave (MW)-assisted catalyst-free and mostly solvent-free Kabachnik-Fields reaction of amino alcohols, paraformaldehyde, and various >P(O)H reagents (dialkyl phosphites, ethyl phenyl--phosphinate, and secondary phosphine oxides) is reported. The synthesis of -2-hydroxyethyl-α-aminophosphonate derivatives was optimized in respect of the temperature, the reaction time, and the molar ratio of the starting materials. A few by-products were also identified. ,-Bis(phosphinoylmethyl)amines containing a hydroxyethyl group were also prepared by the double Kabachnik-Fields reaction of ethanolamine with an excess of paraformaldehyde and secondary phosphine oxides. The crystal structure of a 2-hydroxyethyl-α-aminophosphine oxide and a bis(phosphinoylmethyl)ethanolamine was studied by X-ray analysis.
Topics: Amines; Amino Alcohols; Microwaves; X-Ray Diffraction
PubMed: 31027303
DOI: 10.3390/molecules24081640 -
Enzyme and Microbial Technology Dec 2015Chiral amino alcohols are structural motifs present in sphingolipids, antibiotics, and antiviral glycosidase inhibitors. Their chemical synthesis presents several...
Chiral amino alcohols are structural motifs present in sphingolipids, antibiotics, and antiviral glycosidase inhibitors. Their chemical synthesis presents several challenges in establishing at least two chiral centres. Here a de novo metabolic pathway using a transketolase enzyme coupled with a transaminase enzyme has been assembled. To synthesise this motif one of the strategies to obtain high conversions from the transaminase/transketolase cascade is the use of hydroxypyruvate (HPA) as a two-carbon donor for the transketolase reaction; although commercially available it is relatively expensive limiting application of the pathway on an industrial scale. Alternately, HPA can be synthesised but this introduces a further synthetic step. In this study two different biocatalytic strategies were developed for the synthesis of (2S,3R)-2-amino-1,3,4-butanetriol (ABT) without adding HPA into the reaction. Firstly, a sequential cascade of three enzymatic steps (two transaminases and one transketolase) for the synthesis of ABT from serine, pyruvate and glycolaldehyde as substrates. Secondly, a two-step recycling cascade where serine is used as donor to aminate erythrulose (catalysed by a transketolase) for the simultaneous synthesis of ABT and HPA. In order to test the novel pathways, three new transaminases are described, two ω-transaminases able to accept a broad range of amine acceptors with serine as amine donor; and an α-transaminase, which showed high affinity towards serine (KM: 18mM) using pyruvate as amine acceptor. After implementation of the above enzymes in the biocatalytic pathways proposed in this paper, the two-step recycling pathway was found to be the most promising for its integration with E. coli metabolism. It was more efficient (10-fold higher conversion), more sustainable and cost-effective (use of low cost natural substrates and only two enzymes), and the reaction could be performed in a one-pot system.
Topics: Amino Alcohols; Bacterial Proteins; Biocatalysis; Bioengineering; Biosynthetic Pathways; Kinetics; Pyruvates; Recombinant Proteins; Stereoisomerism; Transaminases; Transketolase
PubMed: 26453469
DOI: 10.1016/j.enzmictec.2015.07.003 -
International Journal For Parasitology.... Aug 2017Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic...
Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical and subtropical countries. Since current chemotherapeutic options are limited and defective, there is an urgent need to develop novel antiplasmodials and antischistosomals. Hemozoin is a disposal product formed from the hemoglobin digestion by some blood-feeding parasites. Hemozoin formation is an essential process for the parasites to detoxify free heme, which is a reliable therapeutic target for identifying novel antiparasitic agents. A series of novel carbazole aminoalcohols were designed and synthesized as potential antiplasmodial and antischistosomal agents, and several compounds showed potent in vitro activities against Plasmodium falciparum 3D7 and Dd2 strains and adult and juvenile Schistosoma japonicum. Investigations on the dual antiparasitic mechanisms showed the correlation between inhibitory activity of β-hematin formation and antiparasitic activity. Inhibiting hemozoin formation was identified as one of the mechanisms of action of carbazole aminoalcohols. Compound 7 displayed potent antiplasmodial (Pf3D7 IC = 0.248 μM, PfDd2 IC = 0.091 μM) and antischistosomal activities (100% mortality of adult and juvenile schistosomes at 5 and 10 μg/mL, respectively) and exhibited low cytotoxicity (CC = 7.931 μM), which could be considered as a promising lead for further investigation. Stoichiometry determination and molecular docking studies were also performed to explain the mode of action of compound 7.
Topics: Amino Alcohols; Animals; Antiparasitic Agents; Carbazoles; Cell Survival; Hemeproteins; Inhibitory Concentration 50; Plasmodium falciparum; Schistosoma japonicum; Survival Analysis
PubMed: 28395189
DOI: 10.1016/j.ijpddr.2017.03.007 -
International Journal of Molecular... May 2024The chiral H-BINOL derivatives R- and R- were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the...
The chiral H-BINOL derivatives R- and R- were efficiently synthesized via a Suzuki coupling reaction, and they can be used as novel dialdehyde fluorescent probes for the enantioselective recognition of R/S-2-amino-1-phenylethanol. In addition, R- is much more effective than R-. Scanning electron microscope images and X-ray analyses show that R- can form supramolecular vesicles through the self-assembly effect of the π-π force and strong hydrogen bonding. As determined via analysis, the fluorescence of the probe was significantly enhanced by mixing a small amount of S-2-amino-1-phenylethanol into R-, with a redshift of 38 nm, whereas no significant fluorescence response was observed in R-2-amino-1-phenylethanol. The enantioselective identification of S-2-amino-1-phenylethanol by the probe R- was further investigated through nuclear magnetic titration and fluorescence kinetic experiments and DFT calculations. The results showed that this mechanism was not only a simple reactive probe but also realized object recognition through an ICT mechanism. As the intramolecular hydrogen bond activated the carbonyl group on the probe R-, the carbonyl carbon atom became positively charged. As a strong nucleophile, the amino group of S-2-amino-1-phenylethanol first transferred the amino electrons to a carbonyl carbocation, resulting in a significantly enhanced fluorescence of the probe R- and a 38 nm redshift. Similarly, S-2-amino-1-phenylethanol alone caused severe damage to the self-assembled vesicle structure of the probe molecule itself due to its spatial structure, which made R- highly enantioselective towards it.
Topics: Stereoisomerism; Amino Alcohols; Hydrogen Bonding; Fluorescent Dyes; Kinetics; Molecular Structure; Models, Molecular; Naphthols
PubMed: 38891794
DOI: 10.3390/ijms25115606 -
Journal of the American Chemical Society Aug 2023Previously, nonenzymatic primer extension reaction of l-threoninol nucleic acid (L-TNA) was achieved in the presence of -cyanoimidazole (CNIm) and Mn; however, the...
Previously, nonenzymatic primer extension reaction of l-threoninol nucleic acid (L-TNA) was achieved in the presence of -cyanoimidazole (CNIm) and Mn; however, the reaction conditions were not optimized and a mechanistic insight was not sufficient. Herein, we report investigation of the kinetics and reaction mechanism of the chemical ligation of L-TNA to L-TNA and of DNA to DNA. We found that Cd, Ni, and Co accelerated ligation of both L-TNA and DNA and that the rate-determining step was activation of the phosphate group. The activation was enhanced by duplex formation between a phosphorylated L-TNA fragment and template, resulting in unexpectedly more effective L-TNA ligation than DNA ligation. Under optimized conditions, an 8-mer L-TNA primer could be elongated by ligation to L-TNA trimers to produce a 29-mer full-length oligomer with 60% yield within 2 h at 4 °C. This highly effective chemical ligation system will allow construction of artificial genomes, robust DNA nanostructures, and xeno nucleic acids for use in selection methods. Our findings also shed light on the possible pre-RNA world.
Topics: Nucleic Acids; DNA; Amino Alcohols; RNA; Nucleic Acid Conformation
PubMed: 37466125
DOI: 10.1021/jacs.3c04979 -
Applied Microbiology Jul 1973Zygosaccharomyces priorianus converted L-tryptophan to tryptophol and to small quantities of indole-3-acetic acid. Neither tryptophol nor indole-3-acetic acid was...
Zygosaccharomyces priorianus converted L-tryptophan to tryptophol and to small quantities of indole-3-acetic acid. Neither tryptophol nor indole-3-acetic acid was metabolized when added separately to growing cultures. The possible intermediacy of indole-3-pyruvic acid, indole-3-acetaldehyde, and tryptamine in the degradation of L-tryptophan was tested by feeding these compounds to Z. priorianus and Saccharomyces cerevisiae. Indole-3-pyruvic acid and indole-3-acetaldehyde were converted to tryptophol and indole-3-acetic acid, with the latter accumulating only in small amounts. Tryptamine was converted to its N-acetyl derivative by these organisms. A qualitative study was made on the metabolism of L-phenylalanine, L-tyrosine, and L-5-hydroxytryptophan by these organisms. Like L-tryptophan, these amino acids were metabolized to their respective alcohol and acid derivatives. Of a large number of organisms tested, the yeasts possessed the highest capacity for degrading L-tryptophan to tryptophol.
Topics: 5-Hydroxytryptophan; Acetaldehyde; Amino Alcohols; Chromatography, Thin Layer; Fermentation; Fluorometry; Indoleacetic Acids; Indoles; Magnetic Resonance Spectroscopy; Phenylalanine; Pyruvates; Saccharomyces; Saccharomyces cerevisiae; Spectrophotometry, Infrared; Stereoisomerism; Tryptamines; Tryptophan; Tyrosine
PubMed: 4580197
DOI: 10.1128/am.26.1.98-105.1973 -
The Journal of Biological Chemistry Aug 1953
Topics: Amino Alcohols; Choline; Glycerophosphates; Hydrolysis; Phosphatidylethanolamines
PubMed: 13084653
DOI: No ID Found -
The Journal of Biological Chemistry Jan 1960
Topics: Amino Alcohols; Lipid Metabolism; Psychosine; Transferases
PubMed: 13810623
DOI: No ID Found -
Angewandte Chemie (International Ed. in... Jun 2022Oligonucleotides are increasingly being used as a programmable connection material to assemble molecules and proteins in well-defined structures. For the application of...
Oligonucleotides are increasingly being used as a programmable connection material to assemble molecules and proteins in well-defined structures. For the application of such assemblies for in vivo diagnostics or therapeutics it is crucial that the oligonucleotides form highly stable, non-toxic, and non-immunogenic structures. Only few oligonucleotide derivatives fulfil all of these requirements. Here we report on the application of acyclic l-threoninol nucleic acid (aTNA) to form a four-way junction (4WJ) that is highly stable and enables facile assembly of components for in vivo treatment and imaging. The aTNA 4WJ is serum-stable, shows no non-targeted uptake or cytotoxicity, and invokes no innate immune response. As a proof of concept, we modify the 4WJ with a cancer-targeting and a serum half-life extension moiety and show the effect of these functionalized 4WJs in vitro and in vivo, respectively.
Topics: Amino Alcohols; Butylene Glycols; Nucleic Acid Conformation; Nucleic Acids; Oligonucleotides; RNA
PubMed: 35352451
DOI: 10.1002/anie.202115275 -
Nature Chemistry Aug 2020Asymmetric, radical C-H functionalizations are rare but powerful tools for solving modern synthetic challenges. Specifically, the enantio- and regioselective C-H...
Asymmetric, radical C-H functionalizations are rare but powerful tools for solving modern synthetic challenges. Specifically, the enantio- and regioselective C-H amination of alcohols to access medicinally valuable chiral β-amino alcohols remains elusive. To solve this challenge, a radical relay chaperone strategy was designed, wherein an alcohol was transiently converted to an imidate radical that underwent intramolecular H-atom transfer (HAT). This regioselective HAT was also rendered enantioselective by harnessing energy transfer catalysis to mediate selective radical generation and interception by a chiral copper catalyst. The successful development of this multi-catalytic, asymmetric, radical C-H amination enabled broad access to chiral β-amino alcohols from a variety of alcohols containing alkyl, allyl, benzyl and propargyl C-H bonds. Mechanistic experiments revealed that triplet energy sensitization of a Cu-bound radical precursor facilitates catalyst-mediated HAT stereoselectivity, enabling the synthesis of several important classes of chiral β-amines by enantioselective, radical C-H amination.
Topics: Amination; Amino Alcohols; Carbon; Catalysis; Copper; Hydrogen; Stereoisomerism
PubMed: 32572164
DOI: 10.1038/s41557-020-0482-8