New Strategy for the Synthesis of Some Valuable Chiral 1,3-Diols with High Enantiomeric Purity: New Organocatalyst, Asymmetric Aldol Reaction, and Reduction.

Chiral 1,3-diols are highly valuable molecules used in industries such as pharmaceuticals, cosmetics, and agriculture. Therefore, in this study, a new strategy was developed to synthesize enantiomerically pure (>99% ee) 1,3-diols. New chiral 1,3-diols (5a-5q) with high enantiomeric purity were synthesized from aldol products chiral 1,3-keto alcohols (4a-4q), which are aldol products with different structures. Chiral 1,3-keto alcohols (4a-4q) were synthesized by a new asymmetric aldol method in the first step. This method was developed using a new proline-derived organocatalyst (3g) and Cu(OTf)2 as an additive in DMSO-H2O for the first time. Almost >99% ee was obtained using our developed aldol procedure. In the second step, original chiral diols (5a-5q) of high enantiomeric purity were obtained by asymmetric reduction of chiral keto alcohols with chiral oxazaborolidine reagents. In this way, a two-step asymmetric reaction was developed for chiral 1,3-diol enantiomers with high enantiomeric purity. The structures of all the original chiral compounds obtained were elucidated by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis methods. Their enantiomeric excesses were determined by the chiral high-performance liquid chromatography method. Both keto alcohols and their corresponding chiral diols synthesized can be used as chiral starting materials and chiral source materials or intermediates in the synthesis of many biologically active molecules, or they can be used as chiral ligands in asymmetric synthesis, serving as organocatalysts.

Investigating the Role of Citric Acid as a Natural Acid on the Crystallization of Amoxicillin Trihydrate.

This study investigates the use of environmentally friendly citric acid as the main player in the process, rather than as an additive, to remove impurities from amoxicillin trihydrate (AMCT) crystals, aiming to optimize their purity and yield. By manipulating the concentration of citric acid, mixing speed, crystallization time, and pH, the researchers conducted experiments using a full factorial design. The dissolution stage was analyzed in both batch and continuous crystallization processes, emphasizing the significance of citric acid in enhancing crystallization. HPLC analyses were performed on the resulting crystals, and the data were analyzed using the Multi-Vari Chart program. The findings demonstrated that higher citric acid concentrations positively affected the yield, while factors such as crystallization time, mixing speed, and pH also contributed to the increased yield. The crystals obtained exhibited desirable dimensions sought after in the pharmaceutical industry, eliminating the need for additional purification steps. This study showcased the potential of citric acid in AMCT crystallization, offering advantages in product design, purification, and synthesis. The optimized conditions included a citric acid concentration of 2.0 M, mixing speed of 1000 rpm, crystallization time of 120 min, and pH of 5.5. Notably, the developed process proved to be environmentally friendly by avoiding the use of harmful chemicals, serving as a green alternative for crystallization processes, and producing purer AMCT products. Overall, this research contributes to the existing literature by highlighting the efficacy of citric acid in impurity removal and the optimization of AMCT crystal purity and yield.

Determination of amoxicillin trihydrate impurities 4-hydroxyphenylglycine (4-HPG) and 6-Aminopenicylanic acid (6-APA) by means of ultraviolet spectroscopy.

Amoxicillin is one of the broad-spectrumß-lactam antibiotics widely used in the treatment of many diseases. It is inevitable that 4-hydroxyphenylglycine (4-HPG) and 6-Aminopenicylanic acid (6-APA), which are used during the production of this antibiotic, are incorporated into the molecular lattice of the product as impurities. Today, many expensive methods and chemical devices are used for the purification of Amoxicillin by determining 6-APA and 4-HPG, which are defined as impurities. In this study, it was aimed to develop a fast, simple, and specific UV-spectrophotometric method for the determination of 4-HPG and 6-APA. Another aim of this article is to cause as little harm as possible to the environment and human health by using as few chemicals as possible throughout the study. In this study, all attempts to determine 6-APA and 4-HPG, which are impurities in the production of amoxicillin, were carried out with the help of a UV/VIS spectrophotometer. Also, Four different concentrations of NaOH were used as a solvent for each impurity. UV spectra of 4-HPG and 6-APA concentrations between 210 and 400 nm were measured. In the literature, the UV spectrum of 4-HPG has been revealed for the first time in this study and examined in detail. The UV spectrum of 4-HPG was characterized in 3 regions. Again, the response of 6-APA to different NaOH concentrations was demonstrated for the first time in this study. It was determined that the peaks of 6-APA dissolved in NaOH shifted from 222 nm to 227 nm depending on the concentration amount. In addition, it is an ideal green procedure that makes a difference in the literature, as the study is carried out for the control and determination of impurities without the use of any organic solvents or chemicals harmful to the environment.

Synthesis and elastase inhibition activities of novel aryl, substituted aryl, and heteroaryl oxime ester derivatives.

Fifteen novel aryl, substituted aryl and heteroaryl γ-hydroxy- (2a-e), γ-methoxyimino- (3a-e), and γ-benzyloxyimino- (4a-e) butyric acid methyl esters were investigated for their enzyme inhibition, and the synthesis of 10 compounds (3a-e, 4a-e) is given in this study. The other five compounds (2a-e) were synthesized before in another study. Compounds 3a-e and 4a-e were synthesized in this work as original compounds and characterized by 1 H and 13 C NMR, IR, mass, and elemental analyses. Their (E/Z)-isomerisation ratios were analyzed by 1 H and 13 C NMR. All of them are of pure (E)-configuration. Due to the literature survey, the elastase inhibition activity was not studied for these compounds. Elastase inhibition ability was investigated in this work for five γ-hydroxy- (2a-e), five γ-methoxy- (3a-e), and five γ-benzyloxyimino- (4a-e) butyric acid methyl esters. All these 15 compounds showed elastase inhibition activity. Compound 2b was the best one and exhibited a better activity than the standard ursolic acid whereas compound 2a worked like the standard. All these compounds can be novel elastase inhibitor agents in the pharmaceutical and cosmetic industries.