Nelson Luís Campos Domingues

The synthesis of sulfur-linked glycosides, such as S-glycosides or S-glycoconjugates, has been extensively explored due to their roles as valuable tools in various biological studies. These compounds can act as glycosidase inhibitors, antibacterial agents, antitumor agents, and more. 1-Thioglycosides are characterized by a sulfur atom bonded to the anomeric position and are rare in nature. Besides their biological and pharmaceutical significance, thioglycosides serve as key substrates for the synthesis of other glycosides (O-, N-, and C-glycosides), glycoconjugates, glycoproteins, and polysaccharides. The growing interest in biologically active S-glycosides stems from their enhanced stability compared to O-glycosides, making them less prone to enzymatic hydrolysis and chemical degradation. This stability underpins their use as enzyme inhibitors and their presence in various drugs and bioactive natural products. Consequently, the development of efficient synthetic methodologies for functionalized 1-thioglycosides remains a critical focus in medicinal and organic chemistry research. This review focuses on recent advances in the synthetic methodologies for functionalized 1-thioglycosides, highlighting key strategies and their potential applications in medicinal chemistry.

Pd ⁰ is well known for catalyzing cross‐coupling reactions, but how this Pd ⁰ specie is obtained in the reaction medium remains unclear. Concepts such as “releasing the ligand from the catalyst” do not completely describe the full redox process, but they are generally accepted as an explanation for Pd ⁰ formation. Herein, we studied the transformation of Pd(Pro) ₂ , a Pd(II) precatalyst, into Pd ⁰ using experimental methods and theoretical calculations via the C–S cross‐coupling reaction involving 5‐chlorobenzofurazan with various thiols. We found that the thiol hydrogen transfer (THT) process is responsible for the formation of Pd ⁰ from Pd(Pro) ₂ . We also observed that the THT process was influenced by the p K _a of the thiol group and enhanced by the addition of a base to the reaction system. Therefore, the base choice also plays a crucial role in Pd ⁰ formation. Furthermore, a wide variety of sulfured compounds derived from 5‐chlorobenzofurazan was obtained in moderate to high yields using a low catalytic loading of Pd(Pro) ₂ with K ₂ CO ₃ over a short reaction time.

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage) and 100 mg/kg of CPA in a single dose (via intraperitoneal) on the 15th day. After the experimental period, blood and organ samples were collected for histopathological and biochemical analyses, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), ascorbic acid (ASA), carbonyl protein, cytokine measurement, and micronucleus testing. The results showed that liposomes containing P. heptaphyllum extract have an antimutagenic effect against damage induced to DNA by CPA, and that they also protect against oxidative stress, as verified by the increase in the antioxidant enzymes SOD and GPx. The improvement in alkaline phosphatase and creatinine markers suggests a beneficial effect on the liver and kidneys, respectively. However, the depletion of GSH in the liver and brain suggests the use of antioxidants for the metabolism of molecules generated in these tissues. In general, these data show good prospects for the use of P. heptaphyllum liposomes as a cancer chemoprotective agent, as well as possible antioxidant action, conceivably attributed to the flavonoids present in the plant extract.

The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca²⁺−ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mice without affecting locomotion or exploration. MTDZ also modulated multiple pathways, including glutamatergic, NO/L−arginine/cGMP, serotonergic (5−HT_1A/1B), opioid, and TRPV1 pathways. Additionally, MTDZ reduced NOx levels and modulated Ca²⁺−ATPase activity. In conclusion, MTDZ effectively alleviated PTX−induced peripheral neuropathy and demonstrated multi-targeted modulation of pain-related pathways. Its ability to modulate multiple pathways, reduce NOx levels, and modulate Ca²⁺−ATPase activity makes it a potential pharmacological candidate for peripheral neuropathy, acute nociceptive, and inflammatory conditions. Further research is needed to explore its therapeutic potential in these areas.

The C–S cross‐coupling reaction is a very efficient and powerful tool for constructing C–S bonds. Despite the well‐reported C–S cross‐coupling protocols using aryl halides, this reaction using sp2‐hybridized nonaromatic halides is still challenging. Herein, we report light‐assisted C–S cross‐coupling between thiols and 5‐chlorobenzofurazan under blue LED irradiation. We used a new nickel catalyst to synthesize 11 unpublished compounds. Furthermore, we assessed the mechanism and the influence of light irradiation on this reaction and proposed a plausible mechanism that is mediated by the excited state of the nickel catalyst promoted by irradiation with blue light and the C–S coupling product formed. Notably, C–S cross‐coupling under light irradiation was performed for the first time using a nickel catalyst in the absence of an external photocatalyst. We demonstrated that because nickel has a low energy barrier for oxidative addition, this protocol proceeded efficiently using chlorine as a leaving group, and the excited state of the nickel catalyst promoted reductive elimination with a lower energy barrier. It is important to mention that the procedure was tolerated by many functional groups within the thiol, affording a greater than 99% yield after reacting for 6 h.

Buchwald precatalyst (XantPhos Pd-G3) was employed for the first time in a C–S cross-coupling reaction involving 2-(4-bromophenyl)benzothiazole or 5-bromo-2,1,3-benzothiadiazole with various benzenethiols in DMF, K2CO3 as a base, under microwave irradiation at 80 °C, 200 W. Good to excellent yields of the desired products were obtained under microwave conditions. Other significant benefits of this synthetic approach are low catalyst loading, short reaction times, and eco-friendly conditions. Additionally, 29 compounds were successfully synthesized, some of which are new in this protocol.

An efficient and unprecedented S-glycosylation reaction of benzo-2,1,3-thiadiazole at the C-5-position using a Pd-G₃ Xantphos palladacycle precatalyst has been described. This methodology showed a high functional group tolerance to the electrophilic partner and can be successfully applied to a variety of β-mono- and di-thiosugar derivatives. A series of thioglycoside derivatives from benzo-2,1,3-thiadiazole were prepared in good to excellent yields under mild and operationally simple reaction conditions.

Microwave irradiated C–S cross-coupling reaction to synthesize 5-aryllthiobenzo-2,1,3-thiadiazole derivatives from a variety of benzene thiols with 5-bromo-2,1,3-benzothiadiazole, catalyzed by Cu(I) iodide and potassium carbonate as a cost-effective base in DMF, was conducted, affording excellent yields of the desired products. Microwave conditions assisted in the development of C–S cross-coupling reaction with higher yields.

The synthesis of biologically active 2‐substituted benzimidazoles and benzothiazoles was developed using Zn(L‐Pro) ₂ as catalyst in ethanol at room temperature in an aerobic oxidative cyclization reaction involving o‐phenylenediamine and 2‐aminothiophenol with various substituted aldehydes. This process offers a quick and eco‐friendly way to synthesize a variety of pharmacologically important benzothiazoles and benzimidazoles.

The high consumption rate of vegetables stimulates the cultivation and increases the demand regarding the adequacy of the production processes. The attack of the pest Plutella xylostella causes high losses by reducing product quality, typifying a phytosanitary problem. This study aimed to verify the bioactivity of aqueous extracts of leaves of Jacaranda decurrens and Jacaranda mimosifolia at concentrations of 5, 10, and 15% on the insect. The choice test was carried out at the laboratory to determine the food effect of plant extracts and evaluate changes in the life cycle of insects exposed to active compounds through the analysis of biological parameters. Plant extracts of J. decurrens and J. mimosifolia presented with phagodeterrent classification in the choice experiments. The three J. decurrens extract concentrations promoted a prolongation of larval and pupal duration, while the duration of individuals treated with J. mimosifolia at 10% was significantly reduced. Occurred reduction in larval survival of individuals treated with aqueous extracts of J. decurrens and J. mimosifolia. Eggs from treatments with aqueous extract of J. decurrens and J. mimosifolia had reduced survival. Pupal survival of individuals treated with extract at 15% showed a significant reduction compared to the treatments at 5% and 10%. Pupae from the treatment with aqueous extract of Jacaranda mimosifolia showed a reduction in biomass in the treatment at 15% differing from the control e 5%. Thus, the aqueous extracts of the species J. decurrens and J. mimosifolia show insecticidal potential in the tests performed on P. xylostella.