Background: Organotin(IV) derivatives have appeared recently as potential biologically active metallopharmaceuticals exhibiting a variety of therapeutic activities. Hence, it is important to study the synthesis of new organotin compounds with low toxicity that may be of pharmacological interest.Objectives: This study focuses on the synthesis of new bis-stannylated derivatives withC2symmetry that could be tested as antifungal agents against two clinical important fungal species,Cryptococcus neoformansandCandida albicans.Methods: The radical addition of triorganotin hydrides (R₃SnH) and diorganotin chlorohydrides (R₂ClSnH) to bis-α,β-unsaturated diesters derived from (S)-BINOL led to the corresponding new bis-stannylated derivatives withC2symmetry. Nine pure organotin compounds were synthesized with defined stereochemistry. Four of them were enantiomerically pure and four were diastereoisomeric mixtures.Results: All new organotin compounds were fully characterized, those with phenyl ligands bonded to tin were the most active compounds against both the strains (Cryptococcus neoformansandCandida albicans), with activity parameters of IC₅₀close to those of the reference drug (amphotericin B).Conclusion: Nine pure organotin compounds with C2 symmetry were synthesized with defined stereochemistry and their antifungal properties were tested against two clinical important fungi with IC values close to those of the reference drug. The structure-containing preferably two or three phenyl groups joined to the tin atom were highly active against both the strains compared with those possessing tri-n-butyl groups.

We present here a new proposal for the “one pot” generation of new 4-thiazolidinones (9a–e) through a multicomponent reaction under microwave irradiation conditions, using aromatic and heteroaromatic amines (8a–e), absolute ethanol as a “green” solvent and modifying the aldehyde group in the glycosidic residue, synthesized from D-mannitol. The study is focused in the variation of the irradiation times and the concentration of thioglycolic acid in order to study the possibility of controlling the structure and/or stereochemistry of the products formed in the reaction. Thiazolidinones 9a–d were obtained with a 69–82% The generation of the corresponding reaction products were monitored by TLC and CG-MS, taking reaction aliquots. The conditions reaction proved to be chemoselective depending on the excess of acid and irradiation times.

In previous studies of our research group, we have selectively generated a pool of new 4-thiazolidinones by three-component reaction, solvent-free and microwave-assisted, between an aldehyde derived from a carbohydrate, a heteroaromatic amine and thioglycolic acid.[i] More recently, we have studied the effect of the addition of a boron organocatalyst on the selective synthesis of a novel under the same reaction conditions.[ii] With the aim of exploring the best reaction conditions for the diastereoselective synthesis of the 1,4-thiazepan-3-ones and 4-thiazolidinones , we have studied not only the effect on solvent variation but also the aggregation of AlCl₃ or different zeolites as Lewis acid catalysts (mordenita, zeolite 13x and ZSM-5). The generation of the corresponding intermediates and reaction products were monitored by CG-MS, taking reaction aliquots every five minutes of reaction. The characterization of the intermediates and corresponding reaction products were performed by NMR spectroscopy. [i] Ocampo, R. A.; Quiroga, A. A.; Koll, L. C; Fascio, M.; D´accorso, N. B. Síntesis y caracterización de 4-tiazolidinonas unidas a heterociclos nitrogenados y sustituidas por un carbohidrato adecuadamente funcionalizado. XX Simposio Nacional de Química Orgánica. Argentina. Buenos Aires. 2015. [ii] Ocampo, R. A.; Quiroga, A. A.; D´accorso, N. B. Estudio de la síntesis estereo y diasteroselectiva de una nueva 1,4-tiazepan-3-ona sustituida por un hidrato de carbono utilizando irradiacion de microondas. XX Simposio Nacional de Química Orgánica. Argentina. Buenos Aires. 2017.

Organotin compounds have shown a wide spectrum of biological effects and have been extensively studied as fungicides, bactericides, acaricides and wood preservative. A large number of papers have reported the use of organotin compounds as bacterial growth inhibitors. The biocide activity of tribenzyl- and dibenzyltin compounds has been informed, but the effect that the methoxyl group in the aromatic ring could have on the activity of the compounds has not been reported in previous literature. For that reason, we performed an in vitro qualitative assay, and evaluated the activity of benzyltri-n-butyltin (I) and 3,5-dimethoxybenzyltri-n-butyltin (II) against the growth of two bacterial strains: Staphylococcus aureus (Gram-positive) and Escherichia Coli (Gram-negative), using agar well diffusion method. In all cases Merck Art 5273 broth was employed. THF was used both as the solvent of choice for the organometallic compound (since the organotin compounds are not water soluble) and as a negative control. Different concentrations I and II were prepared and the activity was determined by measuring the diameter of the inhibition zone (in cm). The results proved not only that the Gram-positive strain is more susceptible to the inhibition growth effect of the organotin compounds evaluated, but also that 3,5-dimethoxybenzyltri-n-butyltin has higher antibacterial activity. According to this preliminary results we conclude that the presence of the methoxyl group in the aromatic ring would enhance the antibacterial activity of the organotin compound tested here.

Single-enantiomer drug candidates are important to many pharmaceutical companies, and therefore, new methods for the preparation of enantiopure compounds are critical for the development of next-generation pharmaceutical products. The use of microwave (MW) irradiation in organic synthesis has become a popular technique to develop and optimize the libraries of compounds synthesis in short reaction time compare to those obtained with the classical thermal methods in pharmaceutical and academic production. Numerous studies in the past ten years, demonstrated that microwave enhanced chemical reactions and that they are faster than conventional heating methods. In previuos studies, we reported the stereoselective radical addition of organotin hydrides to unsaturated TADDOL diesters. These reactions occurred with intramolecular cyclization under inert atmosphere, radical initiator, toluene and 75°C with high yields and stereoselectivity depending on the reactivity and steric bulk of the organotin hydride employed. Here, we decided to study a new method for the synthesis of these macrocycles through the radical addition of different triorganotin hydrides, R₃SnH (R= Me, n-Bu, Ph; Neophyl), to the same insaturated TADDOL diesters, in THF as solvent and under MW conditions. We compared these results with the previous reported method. Under MW conditions, reactions were completed in very short reaction time and neither the products of double hydrostannation nor the products of cyclopolymerization were obtained in both cases. Furthermore, we evaluated the stereoselectivity by ¹¹⁹Sn-NMR spectroscopic analysis in both methods.

Epoxidation reaction has been the subject of numerous investigations and a number of useful methodologies have been studied. The electrophilic reagents used in this epoxidation, react preferentially with electron-rich olefins. For this reason, electron-deficient olefins such us α,β-unsaturated esters react very slowly with low yields. Our group has previously reported the synthesis of enantiomerically pure α-β unsaturated diesters of TADDOL and BINOL. Optically active epoxides are highly versatile intermediates that can be converted into a wide variety of enantiomerically enriched molecules. Because of this, we decided to study the stereoselective di-epoxidation of diacrylate derivatives with C₂-symmetry. First, we studied simple substrates with the intention to extend the results to more complex molecules. Thus, several epoxidation methods were tested on α-β-unsaturated esters with the aim to improve the previously reported data. Among all the experimental conditions tested, mCPBA reagent was the best, giving the glycidic esters derivatives with very good yields and short reaction time compared with reported methods. Due to the fact that the reaction conditions were unsuccessful with the C₂-diacrylate systems, we decided to study the reactivity of these substrates applying DFT calculations. The reactivity of mCPBA, in olefins epoxidation reactions, can be rationalized by frontier orbital interactions. For this reason, we evaluated the coefficients and shape of HOMO OMs of a series of simple esters and TADDOL and BINOL derivatives. We achieved interesting results concerning the reactivity of these compounds.