Abstract in English:

(+)-2,3,9-Trimethoxypterocarpan [(+)-PTC] is a naturally occurring isoflavonoid that exhibits potent antitumor activity, putatively acting through the inhibition of kinesin-5 (Eg5), a mechanism distinct from classic tubulin-targeting agents. However, its preclinical development has been severely hampered by supply limitations, as previous synthetic routes relied on inefficient racemic strategies requiring laborious chiral resolution. Herein, we report a concise, biomimetic, and enantioselective total synthesis of (+)-PTC that overcomes these challenges. The route features a robust ligand-free Suzuki cross-coupling in PEG-400 and utilizes a ruthenium-catalyzed asymmetric transfer hydrogenation coupled with dynamic kinetic resolution (ATH-DKR) as the key stereodefining step. Optimized conditions enabled the scale-up of the key reduction with a low catalyst loading (2 mol%), delivering the pterocarpan core with high optical purity (98% ee) and excellent diastereocontrol. The synthesis was completed in just six steps with 64% overall yield, securing a sustainable supply of the bioactive enantiomer for advanced biological validation and providing divergent access to optically pure isoflavanone analogues.

Abstract in English:

A green, efficient, scalable and regioselective bromination of N-phenyl ureas was developed using NaBr/trichloroisocyanuric acid in methanol at room temperature. The protocol was effective to a range of substituted N-phenyl ureas, giving the corresponding N-(4-bromophenyl) ureas in up to 98% isolated yield under mild conditions. Among the products obtained, N-(4-bromophenyl)morpholine-4-carboxamide proved to be a valuable fungicide candidate against Colletotrichum lindemuthianum, an important pathogen responsible for causing anthracnose on common bean (Phaseolus vulgaris). The in vitro antifungal activity determined by the minimum inhibitory concentration (MIC = 63 mg mL-1) gave the same result of the commercial fungicide thiophanate-methyl.

Abstract in English:

This study describes the development and optimization of a microwave-assisted reductive amination protocol for the synthesis of secondary amines using the Et3SiH/InCl3/MeOH catalytic system. Initially aimed at establishing a robust route for secondary amine derivatives, the investigation revealed a significant competitive pathway leading to the formation of tertiary amine byproducts through over-alkylation. A systematic screening of reaction conditions, using 2-bromobenzaldehyde as a model substrate, demonstrated that microwave irradiation significantly reduces reaction times compared to conventional heating methods while maintaining high conversion rates. The reaction profile was rigorously monitored using high performance liquid chromatography coupled to diode array detection and mass spectrometry (UHPLC-DAD-MS), which allowed for the identification and relative quantification of the product distribution. The substrate scope investigation showed that the selectivity and reaction rates are strongly influenced by the electronic and steric properties of the aromatic substituents, particularly at the ortho-position. Several of the identified tertiary amines were isolated and characterized as novel compounds, as they are not previously described in the literature as byproducts for this system. These findings provide a strategic framework for controlling selectivity in reductive aminations and highlight the importance of detailed byproduct analysis in methodology development, offering new chemical entities for future applications in chemistry.

Abstract in English:

Microwave-assisted Knoevenagel-Doebner condensation mediated by pyridine has proven to be a highly efficient method for the synthesis of 3-aryl acrylic acids, which are important intermediates in the preparation of industrially and pharmacologically relevant compounds. The efficiency of the present approach is demonstrated by high reactant conversion, along with a significant reduction in reaction time compared to conventional heating methods. A comparative study revealed that the use of pyridine as both base and solvent under either conventional reflux or microwave-assisted conditions clearly favors the latter, with reactions proceeding at least eight times faster under microwave irradiation. Furthermore, the method was successfully scaled up for selected target molecules, enabling the synthesis on a 50 mmol scale of cinnamic acid (2a), (E)-3-(furan-2-yl) acrylic acid (2b), and ferulic acid (2e).

Abstract in English:

Raw materials from renewable sources, as well as agro-industrial waste, represent an attractive source of useful chemical functionalities, which to date is still underexplored in terms of their application in the fine chemicals industry. Herein, we present a comprehensive overview of biomass valorization through the application of advanced enabling technologies, including microwave irradiation, continuous flow chemistry, photochemistry and mechanochemistry. These methodologies are evaluated for their significant advantages over traditional batch processes, particularly in terms of enhanced reaction efficiency, scalability, and environmental sustainability. Key examples from our group are provided to illustrate how these technologies streamline biomass conversion into high-value chemicals through more efficient and controlled reaction conditions. Our contributions highlight the transformative potential of these approaches in converting biomass-derived feedstocks into valuable chemical intermediates.

Abstract in English:

Minor phytocannabinoids constitute a structurally diverse class of natural products derived from Cannabis sativa L.; however, their study remains limited due to their low abundance in the plant and the challenges associated with isolation. Consequently, numerous compounds with unique molecular architectures still possess unexplored biological profiles. Herein, we comprehensively review the principal minor phytocannabinoids reported in the literature, addressing their isolation histories, proposed biosynthetic pathways, and reported biological activities, with particular emphasis on their synthetic routes, highlighting key steps. By contextualizing these advances, this review emphasizes the central role of organic synthesis in enabling access to rare phytocannabinoids, thereby facilitating more in-depth pharmacological studies and contributing to the discovery of new bioactive natural products.

Abstract in English:

The development of metal-free strategies for the synthesis of 1,2,3-triazoles has emerged as an important alternative to traditional copper-catalyzed methods. In this review, a comprehensive overview of DBU-driven azide-based [3 + 2] cycloaddition reactions (DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene) for the construction of structurally diverse 1,2,3-triazoles is presented. The role of DBU as a strong, non-nucleophilic organocatalyst is highlighted, particularly in promoting enolate formation and enabling efficient cycloaddition under mild conditions. Key transformations, including azide-carbonyl cycloadditions, reactions with activated alkenes, and multicomponent/tandem processes, are systematically discussed. Mechanistic aspects, substrate scope, regioselectivity, and synthetic applications, especially in medicinal chemistry, are critically analyzed. Overall, this work consolidates current advances and underscores the potential of DBU-mediated methodologies as sustainable and versatile tools for heterocycle synthesis.

Abstract in English:

Late-stage functionalization (LSF) has emerged as a powerful strategy for the direct modification of structurally complex molecules, enabling rapid access to valuable analogues and offering a stepand resource-economical platform for molecular diversification. Transition-metal catalysis has played a central role in advancing these transformations. However, to date, late-stage metal-catalyzed C-H functionalization has relied predominantly on noble transition metals. First-row (3d) transition metals are more abundant, less expensive, and generally less toxic, making them attractive alternative for sustainable LSF applications. In addition, they offer complementary reactivity to their noble metal congeners. This review focuses in the intersection of 3d-metal catalysis, C-H activation, and late-stage functionalization, with particular emphasis on the modifications of aromatic systems in complex molecules. A critical analysis of the key challenges associated with the use of 3d metals in these transformations, including issues related to catalyst reactivity and stability, as well as the chemoand regio-selectivity is provided. By examining the advancements and limitations over the past decade, this review aims to offer insights into emerging strategies to overcome these challenges and to guide the development of more efficient and sustainable methodologies in transition-metal catalyzed C-H functionalization.

Abstract in English:

Erlotinib is an important tyrosine kinase inhibitor in receptors overexpressed in malignant tumors, such as lung cancer, acting directly on the epidermal growth factor receptor. Existing synthetic routes to prepare this drug typically require multiple steps, harsh conditions, or expensive reagents, which limits their scalability and sustainability. Herein, it is described an efficient and cost effective synthesis of erlotinib, comprising only five steps from 3,4-dihydroxybenzaldehyde. The approach is highlighted by a direct Schmidt nitrilation of 3,4-bis(2-methoxyethoxy)benzaldehyde under mild, transition-metal-free conditions, achieving high conversion without the need for oxime intermediates or dehydrating agents. The final cyclization, promoted via a microwave-assisted cyclization, affords erlotinib in high yield. Overall, this route combines synthetic efficiency with methodological improvements, achieving an average yield of 87% per step.

Abstract in English:

5-Amino-1H-1,2,3-triazoles are valuable heterocycles owing to their synthetic versatility, photophysical and biological properties. Herein, we report mechanochemical protocol for the synthesis of 5-amino-1H-1,2,3-triazoles from phenylacetonitriles and arylazides under solvent-free, low-energy milling conditions with SiO2 as a milling auxiliary. Notably, the mechanochemical process affords the desired product by simple filtration. The scope of the reaction was demonstrated with several substituted phenylacetonitriles and arylazides, affording sixteen examples of the corresponding 5-amino-1,4-diaryl-1H-1,2,3-triazoles in good yields (up to 79%). Overall, this mechanochemical method provides a simple and environmentally benign alternative for the preparation of 5-amino-1H-1,2,3-triazoles in short reaction times under mild conditions.

Abstract in English:

This study describes the design, synthesis, and biological evaluation of novel eight chromene-dihydropyrimidinone (Chro-DHPM) hybrids as urease inhibitors. The synthetic approach involved the covalent linkage of chromene and DHPM pharmacophores through a non-enolizable 1,2,3-triazole linker, efficiently constructed via the copper-catalyzed azidealkyne cycloaddition (CuAAC) protocol. Evaluation of antiureolytic activity against urease from Canavalia ensiformis type III revealed that hybrids 4b and 4h were the most potent inhibitors, exhibiting 42.1 and 51.5% inhibition at 100 µM, respectively. These results were compared to thiourea (TIO), used as a positive control, which showed 63.5% inhibition under the same conditions. Furthermore, the hybrids demonstrated significantly enhanced activity compared to their individual precursors, chromene 1a and Biginelli adducts 3b and 3d, thereby highlighting a synergistic effect from molecular hybridization. Molecular dynamics simulations of the most active hybrid, 4h, elucidated a dual binding mechanism wherein the compound stabilizes within the urease active site through coordination of the tetrahydropyrimidine carbonyl oxygen to the binuclear nickel center, combined with steric occlusion of the catalytic entrance by the tetrahydro4H-chromene moiety. Overall, this work demonstrates that molecular hybridization of chromene and DHPM scaffolds represents a promising strategy for developing novel antiureolytic agents.

Abstract in English:

Coumarins are versatile heterocyclic scaffolds widely explored for their photophysical properties and applications in fluorescence-based sensing. In this study, a series of C3-functionalized sulfur-substituted 4-hydroxycoumarins 2a-2k was investigated as potential fluorescent probes for metal ion detection. The compounds were comprehensively characterized using spectroscopic techniques, electrochemical analysis, and density functional theory (DFT) calculations. Photophysical studies revealed intense UV absorption and fluorescence emission in the violet region, with moderate Stokes shifts consistent with intramolecular charge transfer (ICT) transitions. Time-resolved measurements indicated nanosecond-scale excited-state lifetimes, while theoretical calculations supported the ICT nature of the electronic transitions. Preliminary aggregation studies demonstrated aggregation-induced emission (AIE) behavior for derivative 2a, suggesting potential applications in solid-state luminescent systems. Among the investigated compounds, derivative 2k exhibited the most promising sensing performance, showing selective fluorescence quenching toward Hg2+ ions through heavy atom effects and ligand-to-metal charge transfer interactions. Quantitative fluorescence titration revealed a Stern-Volmer constant on the order of 104 M-1, with limits of detection and quantification of 3.66 and 11.10 μM, respectively. Furthermore, the probe demonstrated rapid response, good anti-interference capability, and successful detection of Hg2+ in cosmetic samples. These results highlight sulfur-substituted 4-hydroxycoumarins as promising fluorescent platforms for the development of optical sensors for heavy metal monitoring in environmental and consumer products.

Abstract in English:

α-Nitroolefins are introduced as novel dipolarophiles in [3 + 2] cycloadditions with organic azides, enabling the regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles under metal-free conditions. The α-nitroolefin is generated in situ from the corresponding nitro alcohol-derived acetate. Reaction optimization identified Brønsted acid catalysis in dimethylformamide (DMF) under microwave irradiation as the optimal conditions, affording triazoles in yields up to 71%. The methodology tolerates a range of aryl-substituted α-nitroolefins and aliphatic azides, although aryl azides exhibit diminished reactivity. Computational studies reveal that the cycloaddition proceeds preferentially through a stepwise mechanism. Regioselectivity arises from a combination of favorable frontier molecular orbital interactions and a lower-distortion energy pathway, in which azide deformation plays a dominant role. These findings provide a mechanistic basis for the exclusive formation of 1,4-triazoles and highlight the impact of nitro group positioning on cycloaddition reactivity.

Abstract in English:

The prolinol derivatives are among the most prominent catalysts in aminocatalysis. The installation of silyl ether groups onto the hydroxyl group prevented off-cycle equilibria between iminium intermediates and hemiaminal species, leading to high activity and widespread adoption of these catalysts. However, in the organocatalyzed [3 + 2] cycloaddition of nitrones to propargylic aldehydes, the silyl-protected catalysts proved ineffective, whereas the unprotected catalysts afforded high yields. In this study, this seemingly paradoxical reactivity has been explained using a combination of nuclear magnetic resonance, electrospray ionization mass spectrometry, and infrared photodissociation spectroscopy. Contrary to other reactions, the hemiaminal formation is essential, as it keeps the concentration of free prolinol catalyst in the solution minimal, and thereby hinders the undesired prolinol addition to the iminium intermediate. In the case of silylated catalysts, no hemiaminal can form, and the catalyst is rapidly incorporated into the side product, halting the reaction.

Abstract in English:

Latent fingerprints (LFPs) are a key tool in forensic identification due to their uniqueness and long-term stability. However, their visualization at crime scenes remains challenging, highlighting the need for more efficient development methods. Recent studies have focused on organic compounds exhibiting aggregation-induced enhanced emission (AIEE), with weak luminescence in solution but strong emission in aggregated states. When incorporated into the sebaceous residues of fingerprints, these compounds can significantly enhance luminescence, enabling high-contrast and well-defined LFP images. In this work, new aryloxy-benzothiadiazole (BTD) derivatives were developed for LFP detection. Two compounds, OcA-BTD and Pyr-BTD, were synthesized, each designed according to a distinct fingerprint recognition strategy. For Pyr-BTD, a pyridine moiety was incorporated to promote interactions between the basic nitrogen and amino acids and fatty acids present in LFP residues. In contrast, OcA-BTD was designed with a highly lipophilic octadecyl chain to enhance affinity toward the lipid-rich components of LFPs. As a result, only the octadecyl-substituted compound exhibited pronounced AIEE, showing green emission in the aggregated state. This AIEEgen enabled the clear visualization of levels 1, 2, and 3 on fingerprint details on different substrates, providing excellent contrast between LFPs ridges and furrows.

Abstract in English:

Sulfoxonium ylides have emerged as safer alternatives to diazo compounds for generating metal carbenes in X-H insertion reactions. However, most studies still focus on aryl ester ylides and on a relatively narrow selection of noble metal catalysts. In this work, it was investigated aryl, alkyl, and unsubstituted sulfoxonium ylides (ester, keto and amide) in X-H insertion reactions mediated by metal carbenes. A broad range of catalysts was evaluated under standardized conditions, including noble metals such as Au, Ag, Pt, Pd, Rh, Ir, and Ru, and non-noble metals such as Fe, Cu, Zn, Ni, V, Mn, Co, Zr, and Sc. For the aryl ester ylide, several catalysts promoted N-H insertions in good yields, with notable performance from Ir, Rh, Fe, Ag, Sc, and V complexes. For unsubstituted ylides, only Rh, Ir, and Ru complexes delivered satisfactory results. Based on these data, alkyl ylides were evaluated only with Ir, Rh, and Ru, showing high efficiency for Ir and Rh. The aryl keto ylide displayed distinct behavior, forming mainly the imine and 1,2-dicarbonyl products. O-H and S-H insertions were also carried out for the aryl ester ylide using different catalysts, giving yields between 10-94%.

Abstract in English:

A three-step synthesis of 2,4,5-trisubstituted imidazoles involving Pd-catalyzed α-arylation of aromatic methyl ketones, here represented by 4-acetyl pyridine, with 2-bromo-6-alkoxynaphtalenes, followed by in situ oxidation with selenium dioxide, featuring only two chromatographic purifications, provides the corresponding 1,2-diketones which underwent a Debus-Radziszewski condensation to furnish 2,4,5-trisubstitued imidazoles in moderate to good overall yields (30 examples). The methodology is particularly appropriate for the late-stage introduction of the substituent at C-2 in the imidazole ring and nicely complements previously described methods where the substituent at C-5 was incorporated at the end of the synthetic route.