Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer.

ABSTRACT: The preparative resolution of a trifunctionalized C ₃-symmetrical chiral cyclotriveratrylene derivative was achieved via high-performance liquid chromatography (HPLC) on a chiral stationary phase. This approach is a promising alternative to the previously reported resolution through formation of diastereomeric esters because it involves fewer synthetic steps and is less prone to thermal (re)racemization. During these studies an intermediate saddle conformer could also be isolated and characterized by ¹H and ¹³C NMR spectroscopy. The HPLC separation method was further developed in order to allow investigations on the racemization behavior of the cyclotriveratrylene derivative.

SUBMITTER: Gotz S

PROVIDER: S-EPMC6604736 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer.

Götz Sven S Schneider Andreas A Lützen Arne A

Beilstein journal of organic chemistry 20190618

The preparative resolution of a trifunctionalized <i>C</i> <sub>3</sub>-symmetrical chiral cyclotriveratrylene derivative was achieved via high-performance liquid chromatography (HPLC) on a chiral stationary phase. This approach is a promising alternative to the previously reported resolution through formation of diastereomeric esters because it involves fewer synthetic steps and is less prone to thermal (re)racemization. During these studies an intermediate saddle conformer could also be isolat ...[more]

PMID: 31293683

Similar Datasets

Direct Enantiomeric Resolution of Seventeen Racemic 1,4-Dihydropyridine-Based Hexahydroquinoline Derivatives by HPLC.

Project description:1,4-Dihydropyridine (DHP) scaffold holds an outstanding position with its versatile pharmacological properties among all heterocyclic compounds. Although most of the commercially available DHPs are marketed as a racemic mixture, the chiral center at C-4 can lead to even opposite pharmacological activities between the enantiomers. In the present study, enantioseparation of seventeen DHP structural analogues, consisting of either pharmacologically active or newly synthesized derivatives, (M2-4, MD5, HM2, HM10, CE5, N11, N10, N7, M11, MC6-8, MC13, MD23, and 42IIP) by high-performance liquid chromatography was investigated using immobilized polysaccharide-based chiral stationary phase, Chiralpak IC column. Due to the solvent versatility of the covalently immobilized chiral stationary phase in enantiomer separation, multiple elution modes including standard normal phase, nonstandard mobile phase, and reversed phase were used to expand the possibility to find the optimum enantioselective conditions for the tested analytes. Under appropriate separation conditions, complete enantiomeric separation was obtained for nearly all compounds except MC6-8 and MC13 which contained two chiral centers. Additionally, the effects of the polar modifier, the additive, and column temperature on the chiral recognition were evaluated. The thermodynamic parameters calculated according to the linear van't Hoff equation indicated that the chiral separations in this study were enthalpy-driven or entropy-driven. Some parameters of method validation such as linearity, limit of quantitation, and repeatability were also measured for all studied compounds to prove the reliability of the method.

| S-EPMC6566779 | biostudies-literature

Saddle-shaped tetraphenylenes with peripheral gallic esters displaying columnar mesophases.

Project description:Tetraphenylenes 2 with eight peripheral gallic esters were prepared in two steps from octamethoxytetraphenylene 1 in 19-72% yield. Investigation of the mesomorphic properties of 2 by DSC, POM and X-ray diffraction revealed that derivatives 2a-d with short alkoxy chain lengths (C(5)-C(8)) did not show any mesomorphic properties, whereas compounds 2e-i with C(9)-C(13) chains displayed rectangular columnar mesophases and compounds 2j-l with C(14)-C(16) chains displayed hexagonal columnar mesophases. Furthermore an anomalous odd-even effect of the clearing points of compounds 2e-l versus chain length was detected.

| S-EPMC2813710 | biostudies-literature

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives.

Project description:The synthesis of batch-to-batch reproducible cyclodextrin (CD) derivatives often requires functionalization at specific positions of the CD skeleton. However, the regioselective preparation of this type of CD derivatives remains a challenge in synthetic chemistry. Thus, the present study aimed to prepare all positional regioisomers on the primary rim of homobifunctionalized diazido-α-CDs by selective substitution on the primary rim. Specifically, three positional regioisomers 6A,6B-, 6A,6C-, and 6A,6D-diazido-α-CDs were prepared via different intermediates (using sulfonylation with capping agents, bromination and tosylation). Furthermore, heterobifunctionalized 6A-azido-6X-mesitylenesulfonyl-α-CDs were also synthesized, and all regioisomers were successfully separated by HPLC. Moreover, the heterobifunctionalized α-CD regioisomers were isolated in gram-scale quantities, isomers AB and AC in the form of a pseudoenantiomeric mixture. The pseudoenantiomers AC/CA and AB/BA were resolved on an analytical scale by HPLC-MS at 10 °C. Thus, the presented synthetic and analytical methods for homo- and heterodisubstituted α-CDs are efficient and reproducible for the preparation of various pure regioisomeric CD derivatives. Accordingly, our findings indicate, (i) the versatility of selectively modified azido and mesitylene CD skeletons in preparing new types of α-CD derivatives and (ii) the potential of using resolved α-CD pseudoenantiomers in other research fields such as organocatalysis.

| S-EPMC6244315 | biostudies-literature

Membrane Permeability in a Large Macrocyclic Peptide Driven by a Saddle-Shaped Conformation.

Project description:The effort to modulate challenging protein targets has stimulated interest in ligands that are larger and more complex than typical small-molecule drugs. While combinatorial techniques such as mRNA display routinely produce high-affinity macrocyclic peptides against classically undruggable targets, poor membrane permeability has limited their use toward primarily extracellular targets. Understanding the passive membrane permeability of macrocyclic peptides would, in principle, improve our ability to design libraries whose leads can be more readily optimized against intracellular targets. Here, we investigate the permeabilities of over 200 macrocyclic 10-mers using the thioether cyclization motif commonly found in mRNA display macrocycle libraries. We identified the optimal lipophilicity range for achieving permeability in thioether-cyclized 10-mer cyclic peptide-peptoid hybrid scaffolds and showed that permeability could be maintained upon extensive permutation in the backbone. In one case, changing a single amino acid from d-Pro to d-NMe-Ala, representing the loss of a single methylene group in the side chain, resulted in a highly permeable scaffold in which the low-dielectric conformation shifted from the canonical cross-beta geometry of the parent compounds into a novel saddle-shaped fold in which all four backbone NH groups were sequestered from the solvent. This work provides an example by which pre-existing physicochemical knowledge of a scaffold can benefit the design of macrocyclic peptide mRNA display libraries, pointing toward an approach for biasing libraries toward permeability by design. Moreover, the compounds described herein are a further demonstration that geometrically diverse, highly permeable scaffolds exist well beyond conventional drug-like chemical space.

| S-EPMC10885153 | biostudies-literature

Ruthenium nanoparticles canopied by heptagon-containing saddle-shaped nanographenes as efficient aromatic hydrogenation catalysts.

Project description:The search for new ligands capable of modifying the metal nanoparticle (MNP) catalytic behavior is of increasing interest. Herein we present the first example of RuNPs stabilized with non-planar heptagon-containing saddle-shaped nanographenes (Ru@1 and Ru@2). The resemblance to graphene-supported MNPs makes these non-planar nanographene-stabilized RuNPs very attractive systems to further investigate graphene-metal interactions. A combined theoretical/experimental study allowed us to explore the coordination modes and dynamics of these nanographenes at the Ru surface. The curvature of these saddle-shaped nanographenes makes them efficient MNP stabilizers. The resulting RuNPs were found to be highly active catalysts for the hydrogenation of aromatics, including platform molecules derived from biomass (i.e. HMF) or liquid organic hydrogen carriers (i.e. N-indole). A significant ligand effect was observed since a minor modification on the hept-HBC structure (C[double bond, length as m-dash]CH2 instead of C[double bond, length as m-dash]O) was reflected in a substantial increase in the MNP activity. Finally, the stability of these canopied RuNPs was investigated by multiple addition experiments, proving to be stable catalysts for at least 96 h.

| S-EPMC9667958 | biostudies-literature

Kinetic Resolution of Racemic Mixtures via Enantioselective Photocatalysis.

Project description:Despite the increasing demand for enantiopure drugs in the pharmaceutical industry, currently available chiral separation technologies are still lagging behind, whether due to throughput or to operability considerations. This paper presents a new kinetic resolution method, based on the specific adsorption of a target enantiomer onto a molecularly imprinted surface of a photocatalyst and its subsequent degradation through a photocatalytic mechanism. The current model system is composed of an active TiO2 layer, on which the target enantiomer is adsorbed. A photocatalytic suppression layer of Al2O3 is then grown around the adsorbed target molecules by atomic layer deposition. Following the removal of the templating molecules, molecularly imprinted cavities that correspond to the adsorbed species are formed. The stereospecific nature of these pores encourages enantioselective degradation of the undesired species through its enhanced adsorption on the photocatalyst surface, while dampening nonselective photocatalytic activity around the imprinted sites. The method, demonstrated with the dipeptide leucylglycine as a model system, revealed a selectivity factor of up to 7 and an enrichment of a single enantiomer to 85% from an initially racemic mixture. The wide range of parameters that can be optimized (photocatalyst, concentration of imprinted sites, type of passivating layer, etc.) points to the great potential of this method for obtaining enantiomerically pure compounds, beginning from racemic mixtures.

| S-EPMC8397234 | biostudies-literature

Resolution of Racemic Mixtures by Phase Transition of PEGylated Resolving Agents.

Project description:A novel, efficient, and simple method for the resolution of racemic mixtures is presented in which PEGylated resolving agents are subjected to diastereomeric complex formation in alcohols. The resulting complexes then undergo temperature-assisted phase transition, affording a precipitate that is enriched in one enantiomer and separable by filtration. In an aqueous solution, phase transition can be caused by the methods used in the precipitation of poly(ethylene glycol) (e.g., addition of ammonium sulfate). A number of racemic amines have been successfully resolved using this method. The first cycle of resolution affords the amines with an optical purity of 72-85% from their corresponding racemic mixture in good yields (78-90%). An additional cycle improved the optical purity to 87-95%. The PEGylated resolving agents can be recovered and reutilized without the loss of resolution efficiency.

| S-EPMC6645586 | biostudies-literature

Single Isomer N-Heterocyclic Cyclodextrin Derivatives as Chiral Selectors in Capillary Electrophoresis.

Project description:In order to better understand the chiral recognition mechanisms of positively charged cyclodextrin (CD) derivatives, the synthesis, the pKa determination by 1H nuclear magnetic resonance (NMR)-pH titration and a comparative chiral capillary electrophoretic (CE) study were performed with two series of mono-substituted cationic single isomer CDs. The first series of selectors were mono-(6-N-pyrrolidine-6-deoxy)-β-CD (PYR-β-CD), mono-(6-N-piperidine-6-deoxy)-β-CD (PIP-β-CD), mono-(6-N-morpholine-6-deoxy)-β-CD (MO-β-CD) and mono-(6-N-piperazine-6-deoxy)-β-CD (PIPA-β-CD), carrying a pH-adjustable moiety at the narrower rim of the cavity, while the second set represented by their quaternarized, permanently cationic counterparts: mono-(6-N-(N-methyl-pyrrolidine)-6-deoxy)-β-CD (MePYR-β-CD), mono-(6-N-(N-methyl-piperidine)-6-deoxy)-β-CD (MePIP-β-CD), mono-(6-N-(N-methyl-morpholine)-6-deoxy)-β-CD (MeMO-β-CD) and mono-(6-N-(4,4-N,N-dimethyl-piperazine)-β-CD (diMePIPA-β-CD). Based on pH-dependent and selector concentration-dependent comparative studies of these single isomer N-heterocyclic CDs presented herein, it can be concluded that all CDs could successfully be applied as chiral selectors for the enantiodiscrimination of several negatively charged and zwitterionic model racemates. The substituent-dependent enantiomer migration order reversal of dansylated-valine using PIP-β-CD contrary to PYP-β-CD, MO-β-CD and PIPA-β-CD was also studied by 1H- and 2D ROESY NMR experiments.

| S-EPMC8434369 | biostudies-literature

The Dewar Isomer of 1,2-Dihydro-1,2-azaborinines: Isolation, Fragmentation, and Energy Storage.

Project description:The photochemistry of 1,2-dihydro-1,2-azaborinine derivatives was studied under matrix isolation conditions and in solution. Photoisomerization occurs exclusively to the Dewar valence isomers upon irradiation with UV light (>280 nm) with high quantum yield (46 %). Further photolysis with UV light (254 nm) results in the formation of cyclobutadiene and an iminoborane derivative. The thermal electrocyclic ring-opening reaction of the Dewar valence isomer back to the 1,2-dihydro-1-tert-butyldimethylsilyl-2-mesityl-1,2-azaborinine has an activation barrier of (27.0±1.2) kcal mol-1 . In the presence of the Wilkinson catalyst, the ring opening occurs rapidly and exothermically (ΔH=(-48±1) kcal mol-1 ) at room temperature.

| S-EPMC6214188 | biostudies-literature

Lipase Catalysed Kinetic Resolution of Racemic 1,2-Diols Containing a Chiral Quaternary Center.

Project description:Optically active 1,2-diols are valuable buildings blocks in organic synthesis. In the present paper, a set of racemic 1,2-diols with an ester functional group are prepared, starting from ?-ketoesters in a three-step procedure with moderate yields. The racemic 1,2-diols, containing a chiral quaternary center in their structure, are subjected to selective acylation in order to perform their kinetic resolution catalysed by a set of commercially available lipases. Under optimized reaction conditions, good conversions and enantioselectivities are achieved by using the lipase PSL-C from Pseudomonas cepacia in tert-butyl methyl ether. This biocatalyst could be reused up to five times without losing its properties.

| S-EPMC6100382 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data