1078-21-3Relevant articles and documents
Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
, p. 390 - 398 (2021)
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
Synthesis and Biological Analysis of Anti-addiction Effect and Hepatotoxicity of Tow Baclofen Analogues Complexed with β-Cyclodextrin
Dib, Mohammed El Amine,El Ouar, Ibtissem,Keniche, Assia,Zeghina, Ibtissem
, p. 187 - 196 (2022/02/02)
Aim and Objective: The excessive consumption of alcohol and the installation of dependence is, in most cases, facilitated by favorable psychological factors that trigger and maintain the behavior of consumers. Examples more frequently encountered in individuals having difficulty with alcohol are, in particular: one or more anxiety disorders, deficits in the capacities to manage stress and anxiety. The main objective of this work was to study in vivo the anti-addiction effect and hepatotoxicity of tow baclofen analogues complexed with β-Cyclodextrin (βCD) on an alcohol-dependent rat model. Materials and Methods: The synthesis of two analogues, ABF1 and ABF2, close to baclofen was reported. The structural determination of the two compounds was confirmed by NMR and IR analysis. The complexation of analogues with β-Cyclodextrin (βCD) was performed in water at room temperature (25 °C). The interactions of ABF with β-Cyclodextrin, and the stability constant (Ka) of the inclusion complex formed between them were investigated by using UV-visible spectroscopy. The biological effects of baclofen and the two analogues on alcohol dependence were studied in wistar rats. The anti-addiction effect of the analogues was tested by measuring the alcohol intake and the variation of the animal behaviour. The toxicity of the compounds was also analysed on liver injury markers. Results: The amino-3-phenylbutanoic acid (ABF1) and 3,4,5-trihydroxy-N-(methyl-2-acetate) benzamide (ABF2) were synthesized. The complexation of both analogues of baclofen (BF) with β-cyclodextrin (βCD) (ABF-βCD) was realized and confirmed by the stability constant of the inclusion complex (Ka) and Job’s method. The evaluation of anti-addiction activity in vivo showed that ABF1-βCD inhibits the consumption of alcohol at doses equivalent to those of baclofen. Both baclofen analogues have shown an anxiolytic effect. Regarding the toxicity of the two compounds, our results showed that ABF1-βCD has less toxic effect than baclofen; it reduces the activity of ALT and AST enzymes. Histologically, ABF1-βCD has no effect on the liver structure and has a protective effect against lesions alcohol-induced liver disease. Conclusion: Therefore, it can be suggested that ABF1 analogue combined with β-Cyclodextrin can be used as a treatment for alcohol dependence. Further clinical works are needed to confirm its effectiveness.
Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
supporting information, p. 678 - 682 (2015/03/04)
While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
