Ammonium Formate-Pd/C as a New Reducing System for 1,2,4-Oxadiazoles. Synthesis of Guanidine Derivatives and Reductive Rearrangement to Quinazolin-4-Ones with Potential Anti-Diabetic Activity

1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4CO2H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2′-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics.

A Recommendation for a Pre-Standardized Marine Microalgal Dry Weight Determination Protocol for Laboratory Scale Culture Using Ammonium Formate as a Washing Agent

Microalgal biomass is one of the crucial criteria in microalgal studies. Many reported methods, even the well-established protocol on microalgal dry weight (DW) determination, vary greatly, and reliable comparative assessment amongst published results could be problematic. This study aimed to determine the best condition of critical parameters in marine microalgal DW determination for laboratory-scale culture using four different marine microalgal species. These parameters included the washing process, grades of glass microfiber filter (GMF), GMF pretreatment conditions, washing agent (ammonium formate) concentrations, culture: washing agent ratios (v:v) and washing cycles. GMF grade GF/A with precombustion at 450 °C provided the most satisfactory DW and the highest ash-free dry weight (AFDW)/DW ratio. Furthermore, 0.05 M ammonium formate with 1:2 culture: washing agent ratio and a minimum of two washing cycles appeared to be the best settings of microalgal DW determination. The present treatment increased the AFDW/DW ratio of the four respective microalgae by a minimum of 19%. The findings of this study could serve as a pivotal reference in developing a standardized protocol of marine microalgal DW determination to obtain veracious and reliable marine microalgal DW.

Hydrogenated Palm Fatty Acid Distillate as Raw Materials for Magnesium Stearate Alternatives

Palm fatty acid distillate (PFAD) was used as raw material to produce solid lubricant, or anti-adherent, for confectionery or pharmaceutical products. To improve the degree of saturation, the PFAD was hydrogenated by using two methods: gaseous hydrogenation (GH) and catalytic transfer hydrogenation (CTH) using ammonium formate to produce hydrogenated PFAD (HPFAD). The HPFAD was saponified with MgO to produce magnesium salts of hydrogenated PFAD (Mg-HPFAD). The objective of this research was to investigate the effect of hydrogen concentration and reaction temperature on the iodine value of HPFAD and to investigate the characteristics of paracetamol tablets when using Mg-HPFAD as lubricant compared to commercial Mg-stearate. The HPFAD produced by CTH had a lower iodine value than the HPFAD produced by GH. The lowest iodine value was obtained after CTH using 3.6 M ammonium formate at 90°C. Paracetamol tablets with Mg-PFAD or Mg-HPFAD lubricant showed higher dissolution of active compounds with similar friability, frictiability, and hardness compared to paracetamol tablets with Mg-stearate.

Quantitation of Apremilast in Beagle Dogs Plasma by UPLC-MS-MS and Its Application to Pharmacokinetic Studies

A sensitive and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of apremilast in beagle dog plasma has been developed and successfully validated in the current study. Clopidogrel was employed as an internal standard (IS), and liquid-liquid extraction by tert-butylmethyl ether was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH Shield RP18 column (50 mm × 2.1 mm, 1.7 μm) with 5 mM ammonium formate water and 5 mM ammonium formate methanol as the mobile phase with gradient elution. Calibration plots were linear in the range of 2–3000 ng/mL for apremilast in beagle dog plasma. Mean recoveries of apremilast in beagle dogs plasma ranged from 87.4% to 97.4%. The intrarun and interrun precision was less than 6% and 9%, respectively, with the accuracy between 92.4% and 101.1%. The method has also been successfully applied in the pharmacokinetics study of apremilast. The mean t1/2Z was 5.41 h for 30 mg·day−1 for beagle dogs after oral administration. The AUC0-t increased linearly from 3.51 to 1802.13 μ g L − 1 ∗ h after administration of single doses.

PDA-CAD method for the determination of magnesium, pyridoxine and thiamine in a dietary supplement supported by analytical quality by design methodology

In this research, Analytical Quality by Design (AQbD) methodology was used to develop the HILIC-PDA-CAD method for the determination of magnesium, pyridoxine and thiamine content in a dietary supplement. Experiments were conducted on the Dionex Ulitimate 3000 HPLC system with PDA and CAD detectors. Separations were performed on the ZIC-HILIC PEEK column (100 × 4.6 mm, 5 mm) with a mixture of acetonitrile, acetone and ammonium acetate/ammonium formate aqueous solution (48:12:40, v/v/v) as the mobile phase. The detection was performed at 220 nm. The optimal settings of CAD were defined with the one-factor-at-a-time approach: evaporation temperature 50°C, filter constant 10 s, pressure gas 60 psi. The influence of qualitative (salt type) and quantitative factors (pH and salt concentration) on the magnesium retention factor, k Mg and the selectivity factor between pyridoxine and chloride anion, a B6/Cl-, was tested using the I-optimal design. The design space was defined by Monte Carlo simulations and model coefficients' errors were propagated with the aim of identifying the conditions that meet the following criteria: k Mg <4 and a B6/Cl->3.5, with the probability p=95%. From the derived 2D-Design Space graph, 95 mM of ammonium formate pH 4.4 was selected as the optimal composition of the aqueous phase. The method was validated and its reliability in routine application was confirmed.

Leaching Process of Weathered Crust Elution-Deposited Rare Earth Ore With Formate Salts

To strengthen the rare earth leaching process and weaken the hydration of clay minerals for preventing landslides, it is of great importance to adopt a green and sustainable leaching agent in the industry. In this work, the leaching process of weathered crust elution-deposited rare earth ores with formate salts (ammonium formate, potassium formate, and sodium formate) was investigated. The effects of formate salts on the linear swelling ratio and zeta potential of the clay minerals were studied. The experimental results showed that ammonium formate could effectively recover the rare earth elements from weathered crust elution-deposited rare earth as well as inhibit the leaching of impurity aluminum. At room temperature, when the ammonium formate concentration was 1% wt, the leaching efficiencies of rare earth and aluminum were 87 and 37%, respectively. Compared with traditional inorganic ammonium salts, the inhibition effect of impurity aluminum was obvious. In addition, the results of the linear swelling ratio in the clay minerals showed that the inhibit ability of formate salts on the hydration of clay minerals enhanced with the increase of the formate concentration, and the order of the inhabitation on the clay minerals followed: 1% ammonium formate &gt; 1.5% potassium formate &gt; 2.5% sodium formate &gt; distilled water. Based on the double layer theory, ammonium formate and potassium formate could effectively compress clay mineral particles to avoid water intake, which could increase the interaction between clay mineral particles and greatly reduce the electronegative property of the clay minerals, so as to effectively reduce the surface hydration of clay minerals to decrease the swelling of rare earth ore. The results of this experiment have important and practical significance in guiding the prevention of landslides, promoting the in-situ leaching technology, and effectively protecting the ecological environment in mining areas.

Pd/C Catalyzed Decarboxylation-Transfer Hydrogenation of Quinoline Carboxylic Acids

Abstract:: Pd/C catalyzed decarboxylation-transfer hydrogenation of quinoline carboxylic acids and transfer hydrogenation of quinolines had been developed for the synthesis of 1,2,3,4-tetrahydroquinolines. These two processes were implemented smoothly using Pd/C (0.9 mol%) as catalyst with ammonium formate as hydrogen source in ethanol at 80 oC. The reaction system also can be applied to transfer hydrogenation of benzo[h]quinoline and 2,9-dimethyl-1,10-phenanthroline with good to excellent yields. And the gram scale and recycling of catalyst had been tested with good results. Furtherly, the mechanism of Pd/C catalyzed reduction of quinoline carboxylic acids and quinolines had been proposed.