Combining a flow reactor with spray dryer to allow the preparation of food-grade quality sodium 2-polyhydroxyalkyl-1,3-thiazolidine-4-carboxylates with a low environmental impact

Abstract

The 1,3-thiazolidine-4-carboxylic acid (TCA) and 2-substituted 1,3-thiazolidine-4-carboxylic acids (2S-TCAs) are used as additive prodrugs of cysteine and glutathione in agronomy and in the food and pharmaceutical industries. Using a flow system coupled to a spray dryer, here we prepared the sodium salts of these compounds in powder form. The reaction was carried out using equimolar ratios of l-cysteine, aldehyde, and sodium hydroxide in water as solvent. Formaldehyde, three aldohexoses (d-glucose, d-galactose, d-mannose), three aldopentoses (d-xylose, d-ribose, d-arabinose), and mixtures of these compounds were used as the starting aldehydes. We optimized the pH, reaction temperature, and pump flow rate in order to reach conversions ranging from 55 to 100%. The parameters for spray drying were optimized to reach yields over 79%. Finally, the physical properties of the powders and the stability of these salts in water were measured and compared with those of the corresponding acids. The salts were found to be more stable than acids (13.6 to 17.7% vs. 59.8 to 92.1% to hydrolysis, respectively) after 30 days. As the reactants, the solvent, water, and the base used can be food-grade, the final product would meet the requirements for food-grade quality.