Microwave assisted three component reaction conditions to obtain new thiazolidinones with different heterocyclic skeletons

LORENZO, F. J.; OCAMPO R. A.; MANDOLESI S. D.

Conferencia; 23rd International Electronic Conference on Synthetic Organic Chemistry; 2019

Since the last decades, carbohydrates are no longer considered as simple supporting structures to become important compounds in specific biological activities as well as the advantages of their presence in larger macromolecular structures (low toxicity, low environmental impact, immunogenicity, high functionality and asymmetric sites). Therefore, a new discipline named glycobiology have been developed that is responsible for the study of the biological processes in which carbohydrates are involved [1]. On the other side, heterocyclic compounds containing nitrogen and sulphur like tiazepines and 4-thiazolidinones play an important role in synthetic organic and bioorganic chemistry because of their versatility in the preparation of targets moleculeswith potential biological interest. Tiazepine moiety exhibits important pharmacological properties as antiarrhythmic, antispasmodic, analgesic, anticancer, anti-inflammatory, antidepressive, antidiabetic and antioxidant [2]. Regarding 4-thiazolidinones, many pharmaceutical analogs have the N-C-S bond system in their basic structures and because of this, they are very interesting for studying the hypnotic [3], anticancer [4], antioxidant [5], anti-inflammatory [6], and anti-HIV effects, among others [7].Taking into account that multicomponent reactions (MCRs) is an important synthetic tool [8], we believe that, indeed, the synthesis of new heterocyclic derivatives structurally modified by the presence of a carbohydrate fragment is a wonderful strategy to improve the solubility of the drug and / or decrease its toxicity and immunogenicity starting from a renewable resource of high functionality [9]. Given these facts and based on the versatile bioactivities of the above mentioned structures, we believe that the integration of heteroaromatic amines with carbohydrate scaffold Proceedings 2019 2 of 8 segment through multicomponent reactions free from solvent and microwave assisted, might result a very good way to obtain excellent new drug candidates with unknown or enhanced bioactivities.We have previously study the optimal microwave conditions for the synthetic strategy for the preparation of 4-thiazolidinones (5) starting from 2,3:4,5-di-O-isopropylidene-D-arabino-hexos-2-ulo-2,6-pyranose (1b), mercaptoacetic acid (2) and different aromatic and heteroaromatic amines (3), under 300W and 120°C without solvent (Figure 1) [10]. Depending on the substrate structure, twodifferent type of products could be possible: benzothiazepines (4) and 4-Thiazolidinones (5). Under these reaction conditions, only two diastereoisomers corresponding to 1,3-thiazolidin-4-ones in excellent yields (82 ? 97%) were obtained. Diastereomeric relation in each case was determined by 1H-NMR and GC-MS spectra. Recrystallization from absolute ethanol allowed us to purify one of the diastereoisomer and the characterization of the product was performed by 1H-, 13C, DEPT- HSQCNOESY.2D y 1D selective NOESY - RMN