Synthesis of new enantiopure dimethyl-substituted pyridino-18-crown-6 ethers containing a hydroxymethyl, a formyl, or a carboxyl group at position 4 of the pyridine ring for enantiomeric recognition studies

Kupai, József; Huszthy, Péter; Katz, Marianna; Tóth, Tünde

doi:10.3998/ark.5550190.0013.513

Cited by 4 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We obtained the desired PRDs in two to five steps (Scheme ). We performed a Fenton’s oxidation-type reaction (I, Scheme ) by treating the commercially available dimethyl 2,6-pyridinedicarboxylate ( 1 ) with H 2 O 2 in a solution of Fe(ClO 4 ) 2 in methanol and water in the presence of HClO 4 to introduce the hydroxymethyl group in position 4 of the pyridine core . Hence, we protected the hydroxy group of the intermediate 2 as a tetrahydropyranyl (THP) ether to perform the subsequent transesterification and amidation reactions.…”

Section: Resultsmentioning

confidence: 99%

Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists

et al. 2023

View full text Add to dashboard Cite

Protein kinase C (PKC) modulators hold therapeutic potential for various diseases, including cancer, heart failure, and Alzheimer’s disease. Targeting the C1 domain of PKC represents a promising strategy; the available protein structures warrant the design of PKC-targeted ligands via a structure-based approach. However, the PKC C1 domain penetrates the lipid membrane during binding, complicating the design of drug candidates. The standard docking–scoring approach for PKC lacks information regarding the dynamics and the membrane environment. Molecular dynamics (MD) simulations with PKC, ligands, and membranes have been used to address these shortcomings. Previously, we observed that less computationally intensive simulations of just ligand–membrane interactions may help elucidate C1 domain-binding prospects. Here, we present the design, synthesis, and biological evaluation of new pyridine-based PKC agonists implementing an enhanced workflow with ligand–membrane MD simulations. This workflow holds promise to expand the approach in drug design for ligands targeted to weakly membrane-associated proteins.

show abstract

Section: Resultsmentioning

confidence: 99%

Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Large-scale, multiwell interwell tracing also necessitates the deployment of multiple chemically distinct tracer entities, particularly so in the case of simultaneous tracer injection. Previous experiments − have shown that chemical modification of a ligand such as DPA may be achieved via functionalization at the pyridyl 4-position to generate various derivatives, the exact nature of which are application-dependent. For our purposes, we propose that simultaneous full-field deployment of chemical water (nonpartitioning) tracers may be realized in modular synthetic sequences that enable access to higher-order molecular constructs based on a parent tracer compound through chemical conjugation of differing molecular fragments.…”

Section: Introductionmentioning

confidence: 99%

Zwitterionic Dipicolinic Acid-Based Tracers for Reservoir Surveillance Application

Shi

Thomas

et al. 2021

Ind. Eng. Chem. Res.

View full text Add to dashboard Cite

Chemical tracing within oil reservoirs enables the determination of fluid allocation and interwell flow characteristics for improving injection fluid sweep efficiency and reservoir management, and thus novel instrument-readable, independently distinguishable tracers with ultralow sensitivity and detectability are highly desired. We present a series of dipicolinic acid (DPA)-based molecules as a new class of water tracers for reservoir surveillance applications, demonstrating the design and synthesis of three novel DPA-based molecules confirmed and characterized via NMR and mass spectroscopy. Further installation of zwitterionic functional groups onto the structure of these DPA-based tracer candidates leads to marked reductions in their dynamic rock retention, as demonstrated via core flooding experiments. From an optical detection standpoint, all synthesized DPA derivatives exhibit strong chelation with rare earth ions such as terbium (Tb 3+ ) and emit long-lived fluorescence characteristic of lanthanide chelates, making them detectable using time-resolved fluorescence spectroscopy down to the parts-per-trillion (ppt) level. The time-resolution component is critical for their application as water tracers in reservoir fluids, enabling bypassing of background fluorescence from crude oil and other interferents present in brine. Results show that the stepwise derivatization of native DPA and its analogues generates a suite of molecular structures that can be effectively separated and identified using high-performance liquid chromatography (HPLC). Studies on long-term thermal stability at 100 °C and orthogonal detection by optical and chromatographic methods have demonstrated that the newly developed DPA-based ligands described herein have great potential to serve as highly traceable interwell oilfield tracers.

show abstract

“…The macrocyclization reaction was carried out with pyridino-2,6-dicarbonyl dichlorides (14)(15)(16) [prepared in situ from the corresponding dicarboxylic acids (17 23,24 , 18 25,26 and 19 [25][26][27][28] )] and chiral diamines [(S,S)-9, (S,S)-10] and resulted in new amide type pyridino-crown ethers [(S,S)-1-(S,S)-6, see Scheme 2]. These reactions used the high dilution technique.…”

Section: Scheme 1 Preparation Of New Methyl-[(ss)-9] and Isobutyl-smentioning

confidence: 99%

Synthesis and determination of pKa values of new enantiopure pyridino- and piperidino-18-crown-6 ethers

Kupai

Kisszékelyi

Rojik

et al. 2016

Arkivoc

Self Cite

View full text Add to dashboard Cite

This paper reports the preparation of eight new enantiopure amide type crown ethers and their optically active precursors. Chiral diamines were transformed to amide type pyridino-crown ethers reacting them with pyridine dicarbonyl dichlorides by high dilution technique. Two of the new pyridino-crown ethers were reduced to their piperidino analogues. A preliminary study for the potential application of nanofiltration in the purification and recovery of crown ethers is presented. According to the pK a measurements these eight new macrocycles are potential organocatalysts (for instance in Michael addition reactions) thanks to their acidic and basic moieties and chiral skeletons, respectively.

show abstract

Synthesis of new enantiopure dimethyl-substituted pyridino-18-crown-6 ethers containing a hydroxymethyl, a formyl, or a carboxyl group at position 4 of the pyridine ring for enantiomeric recognition studies

Cited by 4 publications

References 27 publications

Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists

Expanding the Paradigm of Structure-Based Drug Design: Molecular Dynamics Simulations Support the Development of New Pyridine-Based Protein Kinase C-Targeted Agonists

Zwitterionic Dipicolinic Acid-Based Tracers for Reservoir Surveillance Application

Synthesis and determination of pKa values of new enantiopure pyridino- and piperidino-18-crown-6 ethers

Contact Info

Product

Resources

About