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Molecules (Basel, Switzerland) Oct 2022For the first time, monoterpene trifluoromethylated β-hydroxy-benzyl--oximes were synthesized in 81-95% yields by nucleophilic addition of the Ruppert-Prakash reagent...
For the first time, monoterpene trifluoromethylated β-hydroxy-benzyl--oximes were synthesized in 81-95% yields by nucleophilic addition of the Ruppert-Prakash reagent (TMSCF) to the corresponding β-keto-benzyl--oximes based on (+)-nopinone, (-)-verbanone and (+)-camphoroquinone. Trifluoromethylation has been determined to entirely proceed chemo- and stereoselective at the C=O rather than C=N bond. Trifluoromethylated benzyl--oximes were reduced to the corresponding α-trifluoromethyl-β-amino alcohols in 82-88% yields. The structure and configuration of the compounds obtained have been established.
Topics: Amino Alcohols; Molecular Structure; Monoterpenes; Indicators and Reagents; Oximes
PubMed: 36296661
DOI: 10.3390/molecules27207068 -
International Journal of Molecular... Mar 2022Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to...
Eugenol, 4-allyl-2-methoxyphenol, is the main constituent of clove essential oil and has demonstrated relevant biological activity, namely anticancer activity. Aiming to increase this activity, we synthesized a series of eugenol β-amino alcohol and β-alkoxy alcohol derivatives, which were then tested against two human cancer cell lines, namely gastric adenocarcinoma cells (AGS) and lung adenocarcinoma cells (A549). An initial screening was performed to identify the most cytotoxic compounds. The results demonstrated that three β-amino alcohol derivatives had anticancer activity that justified subsequent studies, having been shown to trigger apoptosis. Importantly, the most potent molecules displayed no appreciable toxicity towards human noncancer cells. Structure-activity relationships show that changes in eugenol structure led to enhanced cytotoxic activity and can contribute to the future design of more potent and selective drugs.
Topics: Alcohols; Amino Alcohols; Antineoplastic Agents; Apoptosis; Clove Oil; Eugenol; Humans
PubMed: 35409123
DOI: 10.3390/ijms23073759 -
Progress in Lipid Research Jul 2019Sphingoid bases encompass a group of long chain amino alcohols which form the essential structure of sphingolipids. Over the last years, these amphiphilic molecules were... (Review)
Review
Sphingoid bases encompass a group of long chain amino alcohols which form the essential structure of sphingolipids. Over the last years, these amphiphilic molecules were moving more and more into the focus of biomedical research due to their role as bioactive molecules. In fact, free sphingoid bases interact with specific receptors and target molecules, and have been associated with numerous biological and physiological processes. In addition, they can modulate the biophysical properties of biological membranes. Several human diseases are related to pathological changes in the structure and metabolism of sphingoid bases. Yet, the mechanisms underlying their biological and pathophysiological actions remain elusive. Within this review, we aimed to summarize the current knowledge on the biochemical and biophysical properties of the most common sphingoid bases and to discuss their importance in health and disease.
Topics: Animals; Cell Membrane; Humans; Molecular Structure; Sphingolipids; Sphingosine
PubMed: 31132366
DOI: 10.1016/j.plipres.2019.100988 -
Molecules (Basel, Switzerland) Oct 2021A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully...
A series of β-amino alcohols were prepared by the reaction of eugenol epoxide with aliphatic and aromatic amine nucleophiles. The synthesized compounds were fully characterized and evaluated as potential insecticides through the assessment of their biological activity against insect cells, compared with a commercial synthetic pesticide (chlorpyrifos, CHPY). Three derivatives bearing a terminal benzene ring, either substituted or unsubstituted, were identified as the most potent molecules, two of them displaying higher toxicity to insect cells than CHPY. In addition, the most promising molecules were able to increase the activity of serine proteases (caspases) pivotal to apoptosis and were more toxic to insect cells than human cells. Structure-based inverted virtual screening and molecular dynamics simulations demonstrate that these molecules likely target acetylcholinesterase and/or the insect odorant-binding proteins and are able to form stable complexes with these proteins. Encapsulation assays in liposomes of DMPG and DPPC/DMPG (1:1) were performed for the most active compound, and high encapsulation efficiencies were obtained. A thermosensitive formulation was achieved with the compound release being more efficient at higher temperatures.
Topics: Amino Alcohols; Animals; Apoptosis; Cell Survival; Cells, Cultured; Eugenol; Humans; Insecticides; Models, Molecular; Molecular Structure; Spodoptera
PubMed: 34771025
DOI: 10.3390/molecules26216616 -
Chemical & Pharmaceutical Bulletin 2021Catalytic chemoselective reactions of innately less reactive functionalities over more reactive functionalities are described. A cooperative catalyst comprising a soft... (Review)
Review
Catalytic chemoselective reactions of innately less reactive functionalities over more reactive functionalities are described. A cooperative catalyst comprising a soft Lewis acid/hard Brønsted base enabled chemoselective activation of a hydroxyl group over an amino group, allowing for nucleophilic addition to electron-deficient olefins. The reaction could be applicable for a variety of amino alcohols, including pharmaceuticals, without requiring a tedious protection-deprotection process. Chemoselective enolization and subsequent α-functionalization of carboxylic acid derivatives were also achieved by a redox active catalyst through the radical process, providing unnatural α-amino/hydroxy acid derivatives bearing a complex carbon framework and a diverse set of functionalities. The present chemoselective catalysis described herein offers new opportunities to expand the chemical space for innovative drug discovery research.
Topics: Alkenes; Amino Alcohols; Carboxylic Acids; Catalysis; Drug Development; Lewis Acids; Molecular Structure
PubMed: 34078797
DOI: 10.1248/cpb.c21-00092 -
Chemical Communications (Cambridge,... Feb 2022Herein, a new strategy for the direct synthesis of functionalized pyrroles from β-amino alcohols and ynones ruthenium-catalyzed acceptorless dehydrogenative coupling...
Herein, a new strategy for the direct synthesis of functionalized pyrroles from β-amino alcohols and ynones ruthenium-catalyzed acceptorless dehydrogenative coupling has been demonstrated. This developed methodology proceeds in an atom- and step-economic fashion together with the merits of broad substrate scope, operational simplicity, and water and hydrogen gas as the sole by-products, which provides an alternative and sustainable way to access functionalized pyrroles. Further, this method was applied to the rapid synthesis of the COX-1/COX-2 inhibitor and boron dipyrromethene derivative successfully.
Topics: Amino Alcohols; Catalysis; Hydrogenation; Ketones; Molecular Structure; Pyrroles; Ruthenium
PubMed: 35080540
DOI: 10.1039/d1cc07018e -
Angewandte Chemie (International Ed. in... Sep 2022Axially chiral biaryl diols have achieved great success in asymmetric catalysis. By contrast, axially chiral biaryl amino alcohols are far less developed. Herein, we...
Axially chiral biaryl diols have achieved great success in asymmetric catalysis. By contrast, axially chiral biaryl amino alcohols are far less developed. Herein, we have rationally designed a versatile C -symmetric biaryl amino alcohol scaffold 1-(1-amino-pyrrol-2-yl)naphthalen-2-ol (NPNOL) on the basis of axially chiral C2-arylpyrrole framework. For its enantioselective synthesis, the chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and azoalkenes had been established. By using this practical method, a wide range of NPNOLs were readily prepared in high yields and excellent atroposelectivities (38 examples, up to 89 % yield and 99 % ee). DFT calculations were performed to reveal the reaction mechanism and the origins of the enantioselectivity. The easy transformations of NPNOL-derived products into organocatalysts/ligands and their preliminary applications in asymmetric catalytic reactions demonstrated the promising utility of NPNOL.
Topics: Amino Alcohols; Catalysis; Ligands; Stereoisomerism
PubMed: 35727301
DOI: 10.1002/anie.202207517 -
The Journal of Organic Chemistry Jul 2021A base-free and acceptorless Ru-catalyzed dehydrogenative approach has been developed for the synthesis of -heterocycles by using 1,3-dicarbonyls and amino alcohols...
A base-free and acceptorless Ru-catalyzed dehydrogenative approach has been developed for the synthesis of -heterocycles by using 1,3-dicarbonyls and amino alcohols through a domino sequential enamine formation and intramolecular oxidative cyclization strategy. This unified approach is also applicable for the synthesis of O-heterocycles involving 2-hydroxybenzyl alcohol as a coupling reactant via consecutive C-alkylation and intramolecular cyclization steps. The present protocol is general for the synthesis of varieties of biologically important scaffolds, such as tetrahydro-4-indol-4-one, 3,4-dihydroacridin-1(2)-one, and tetrahydro-1-xanthen-1-ones derivatives using a single catalytic system, viz. RuHCO(PPh). Environmentally benign HO and H are the only byproducts in this domino process. Moreover, RuHCO(PPh)-catalyzed C3-alkylation of tetrahydro-4-indol-4-one using alcohol as a alkylating partner is also described in this report. For the first time, a solvent-free gram-scale reaction for the acceptorless dehydrogenative annulation has been demonstrated. A plausible mechanism for the Ru-catalyzed base-free and acceptorless dehydrogenative annulation of amino alcohols or 2-hydroxybenzyl alcohols has been provided with several experimental investigations and spectroscopic evidence.
Topics: Alkylation; Amino Alcohols; Catalysis; Cyclization
PubMed: 34151556
DOI: 10.1021/acs.joc.1c00714 -
Chemistry (Weinheim An Der Bergstrasse,... May 2022The intramolecular hydrogen bond (intra-HB) is one of the best-known examples of non-covalent interactions in molecules. Among the different types of intramolecular...
The intramolecular hydrogen bond (intra-HB) is one of the best-known examples of non-covalent interactions in molecules. Among the different types of intramolecular hydrogen bonding, the NH⋅⋅⋅O hydrogen bond in amino-alcohols and amino-ethers is one of the weakest. In contrast to the strong OH⋅⋅⋅N intramolecular hydrogen bond, the strength of the NH⋅⋅⋅O bond can hardly be measured with conventional spectroscopic methods, even for simple amino-alcohols, since the band belonging to the NH⋅⋅⋅O conformer merges with the free OH band. In this work, we developed a combination of G4 calculations, and a method based on experimental vaporization enthalpies to determine the NH⋅⋅⋅O hydrogen bonding strength. The archetypal compounds for this study are 2-amino-1-ethanol and 3-amino-1-propanol as well as their respective methoxy analogs. Based on these molecules, different series were studied to investigate various factors influencing NH⋅⋅⋅O intra-HB strength. In the first series, the influence of alkylation near the hydroxy or methoxy group and the amino group in sterically hindered aminoalcohols was examined. In the second series, the influence of alkylation of the amino-group was investigated. In the third series, the effect of extending the alkyl chain between functional groups was studied.
Topics: Amino Alcohols; Ethers; Hydrogen; Hydrogen Bonding; Thermodynamics
PubMed: 35293642
DOI: 10.1002/chem.202200080 -
Chemical Communications (Cambridge,... Nov 2022Chiral β-heteroaryl amino alcohols are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds...
Chiral β-heteroaryl amino alcohols are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective hydrogenation of α--heteroaryl ketones was realized with a ruthenium-diphosphine-diamine catalyst, providing the corresponding chiral β-heteroaryl amino alcohols with up to 99% yield and up to >99% ee. The synthetic utilities of the current reaction were demonstrated by gram-scale synthesis of key intermediates of Sertaconazole and Cenobamate.
Topics: Hydrogenation; Amino Alcohols; Stereoisomerism; Ruthenium; Catalysis
PubMed: 36305213
DOI: 10.1039/d2cc03701g