Process Development and Scale-Up of a Novel Atypical DAT Inhibitor (S)-CE-123.

Large-scale syntheses of small molecules and kilo laboratories are crucial steps in drug development, especially in advanced stages. (S)-5-((Benzhydrylsulfinyl)methyl)thiazole, (S)-CE-123, a potent, selective, and novel atypical DAT inhibitor, has undergone iterative testing as part of the preclinical evaluation step. This required the process transfer, scale-up, and synthesis of a 1 kg preclinical batch. The Kagan protocol for asymmetric sulfide to sulfoxide oxidation was successfully applied within a four-step synthetic process for the successful upscaling of (S)-CE-123. During the scale-up of the last step, several changes were made to the original synthetic procedure, as with every increase in batch size, new problems had to be overcome. These include, among others, the workup optimization of the last step, the simplification of chromatographic purification, elution modification to improve the purity of the product and saving of workup time. Two washing steps were added to the original procedure to enhance both the yield and the enantiomeric excess value of the final product. The modifications introduced allowed access to a 1 kg (S)-CE-123 batch with a purity >99% and an enantiomeric excess value of 95%.

Geothermal food dehydrator system, operation and sensory analysis, and dehydrated pineapple quality.

Food dehydration is a preservation technique that guarantees its supply. Food like vegetables and fruits are traditionally dehydrated with natural gas or solar energy, however, this work demonstrates the feasibility of doing it with energy from a geothermal power plant in Nayarit, Mexico. Different species of pineapple (Miel, Cayenne, and Esmeralda) were dehydrated at different temperatures from 64 to 80°C and the safety of the product was subsequently verified, for these aerobic mesophiles (<230 ufc/g), total coliforms (<0.3 s.m.), molds and yeasts (<120 v.e.), and salmonella spp (Absent in 25 g), and results were obtained within the proposed specifications, which were generated taking as reference the national and international guidance standards. A sensory evaluation, a modified Flash Profile (mFP), was carried out with a group of judges trained in descriptive methodology, since a better consensus of responses was obtained, thus demonstrating the usability of mFP for food dehydration. The studies of pineapple allowed the evaluation of production with the DGA 200 technology, and the microbiological standards, as well as sensory and physicochemical parameters, were considering just to verify that product is suitable for human consumption. The technology is a system that takes advantage of the heat of the earth, with which it is possible to work 7 days a week or the entire pineapple season. Physicochemical changes caused by its dehydration with respect to the content of vitamin C, carbohydrates, and dietary fiber in the three species of dehydrated pineapple were measured. In the fresh samples, an average concentration of vitamin C 9 mg/100 g, carbohydrates 11.6 g sugar/100 g, and dietary fiber 0.96% were measured. The dehydrated samples presented an average value of vitamin C of 95 mg/100 g, carbohydrates 72.6 g sugar/100 g, and dietary fiber 8.6%, these results were similar to Mühlbauer and Müller, 2020, Drying atlas, drying kinetics and quality of agricultural products, Elsevier.

Synthesis of potentially bioactive PABA-related N-(aminoalkyl)lactamic amino acids and esters via selective S(N)Ar reactions.

Potentially bioactive N-(aminoalkyl)lactamic amino acids and esters were synthesized in satisfactory to good yields by S(N)Ar reactions of aromatic acids with N-(3-aminopropyl)lactams followed by esterification with tertiary amino alcohols. The addition-elimination S(N)Ar mechanism was confirmed by NMR and MS measurements.