Current Organic Chemistry - Online First

The great majority of people on the planet suffer from cancer, one of the main worldwide diseases. The unchecked proliferation of the body's cells makes it one of the most challenging and intricate illnesses to manage. After cardiac disease, it is regarded as one of the primary causes of mortality globally. Numerous anticancer drugs have been developed over time, and their safety is still being evaluated. Among them, Schiff base derivatives are one of the key contributors to cancer treatment worldwide. Often referred to as imines or azomethines, they stand out as fundamental organic moieties that have continuously transformed medicinal chemistry. This versatile moiety serves not only as a key intermediate and linker but also as a fundamental scaffold in the synthesis of biologically active molecules. This review examines non-metallic and non-cyclic imine derivatives as potential anticancer agents, along with their synthetic schemes and structure-activity relationships (SARs). Some Schiff base-based drugs in clinical trials, with their primary action and structure, are also tabulated. By integrating these insights, the review describes how these compounds are being reimagined as potential targeted therapeutic agents in oncology. This comprehensive analysis is designed to guide researchers in developing and designing next-generation anticancer drugs that take advantage of the unique pharmacological properties of Schiff bases with minimal adverse effects.

Heterocyclic compounds, owing to their structural diversity and unique chemical properties, play a core role in various scientific disciplines, particularly in the evolution of pharmaceuticals. Among these, Benzimidazole (BZID) has captured notable interest due to its remarkable medicinal properties and versatility in biological applications. The pharmaceutical value of BZID is further enhanced by its ability to introduce diverse substitutions at its core, making it a crucial framework in the design of numerous therapeutic agents. However, the need for efficient and sustainable synthetic strategies to explore the full potential of BZID derivatives endures as a key concern. This review article highlights and addresses this gap by examining recent advancements in synthesizing BZID derivatives using aniline derivatives or o-phenylenediamine with aldehydes, acids, alcohols, and their derivatives, as well as amines and halo compounds. This paper discusses various innovative techniques, including ionic liquid catalysis, nano-catalysis, and microwave-assisted methods are emphasized for improving the efficiency and sustainability of reactions. Furthermore, it provides a detailed analysis of the various biological activities of BZID derivatives, such as antibacterial, antifungal, antiviral, and anticancer properties. This article highlights the growing interest in BZID derivatives in modern medicine, as well as underscores their unexplored directions for drug discovery and development.

Chiral salen ligands, distinguished by their exceptional spatial and electronic tunability, serve as pivotal scaffolds in asymmetric catalysis, forming stable complexes with diverse metal ions through a robust [O,N,N,O] tetradentate coordination motif derived from the condensation of vicinal diamines with salicylaldehyde derivatives; this review consolidates advances over the past two decades, encompassing synthetic methodologies, structural evolution, and catalytic applications, where Mn-salen complexes facilitate enantioselective oxidations with high stereocontrol, exemplified by oxidative kinetic resolution of secondary alcohols and sulfide oxidations, Co-salen complexes exhibit unparalleled efficiency in hydrolytic kinetic resolution and CO2/epoxide copolymerization, achieving quantitative conversions and exceptional enantiomeric excesses (ee >99%), and Ti-salen systems deliver high enantioselectivity in sulfide oxidations across diverse substrates due to broad electronic tolerance. Innovative extensions include enantioselective olefin epoxidation, asymmetric nitroalkene cyanation, and sustainable polycarbonate synthesis from CO2, offering significant advantages such as low toxicity, recyclability, and operational efficiency in aqueous media, while computational studies provide mechanistic insights, elucidating atomic-level behavior and the electronic origins of catalytic performance; future research priorities emphasize machine learning-guided design of programmable derivatives, development of redox-tunable electrocatalytic platforms, and lifecycle-optimized synthesis to enhance stability, selectivity, and reusability, thereby underscoring the structural versatility of salen scaffolds in advancing green chemistry, pharmaceutical synthesis, and CO2 utilization, with interdisciplinary innovation addressing current challenges to unlock full potential in sustainable catalysis and refine performance metrics for practical implementation.

Sulfonium salts have emerged as versatile precursors in constructing C-C and C-X bonds with enhanced selectivity and functional group tolerance. This review mainly summarizes advancements from 2019 to 2025 in transition-metal-catalyzed cross-coupling methodologies utilizing sulfonium salts, emphasizing their unique advantages over traditional alkyl halides. Key methodologies, including photoredox catalysis, nickel- and palladium-catalyzed transformations, are discussed. Innovations in synthesizing complex molecules, such as 2-benzylpyrrolidines, and arylindoles, are featured. This review also discusses various reaction mechanisms and strategies for site-selective functionalization. We hope this review will promote the development of sulfonium salts.

Quinoline derivatives are considered highly promising for developing anticancer drugs due to their ability to disrupt essential cellular processes by inserting themselves between DNA base pairs. This interference inhibits crucial activities like DNA replication and transcription, making these compounds effective against cancer cells, thereby further boosting their potential to improve overall treatment outcomes. The synthesis of quinoline derivatives involves several named reactions such as the Riehm Quinoline Synthesis, Doebner reaction, Doebner Miller reaction, Gould-Jacobs reaction, Conrad-Limpach synthesis, Combes quinoline synthesis, Skraup reaction, and many others. Furthermore, the novel innovations by various researchers described in this article allow for the production of novel derivatives with specific substitution patterns and biological activities, enabling researchers to optimize pharmacological properties like bioavailability and target specificity. Recent studies have yielded quinoline derivatives that exhibit an increased ability to kill cancer cells and greater specificity for different types of cancer. Moreover, many researchers have demonstrated the strong effectiveness of quinoline derivatives against tumors in early-stage testing, setting the stage for continued research and clinical trials. Thus, quinoline derivatives show great potential in combating cancer, presenting new opportunities for developing innovative therapies for cancer treatment.

Thiophene and its substituted analogs play a significant role in medicinal chemistry due to their diverse biological activities and their importance as versatile synthons in drug design, discovery, and development. These include antimicrobial, antioxidant, anticancer, antitubercular, antirheumatic, anti-urease, anticonvulsant, antileishmanial, and anti-anxiety properties, underscoring its potential as a useful scaffold. Various thiophene derivatives have been reported to exhibit antimicrobial efficacy against multidrug-resistant strains by disrupting membrane permeability and inhibiting enzymes. Structural modifications, such as the introduction of electron-donating substituents, enhance their antioxidant capacity by stabilizing reactive oxygen species. In anticancer applications, these compounds target apoptosis pathways and inhibit enzymes essential for cancer cell survival. The aromatic structure of thiophene facilitates receptor binding and blood-brain barrier penetration in antianxiety applications. Notably, two thiophene-based drugs, tiaprofenic acid and tinoridine, have been investigated in clinical trials for their anti-inflammatory and analgesic properties. Overall, thiophene derivatives have emerged as versatile compounds in medicinal chemistry, offering a broad spectrum of biological activities. This review presents a comprehensive overview of the remarkable progress achieved through the exploration of various reactive sites within the thiophene synthon. It also highlights diverse synthetic approaches employed in the development of both existing and novel thiophene derivatives. This review aims to assist researchers and medicinal chemists in developing novel leads featuring the thiophene moiety, with a focus on identifying promising candidates for future drug development and advancements in medicine.

Ulmus, a genus in the family Ulmaceae, includes medicinal plants traditionally used to treat pain and bone-related disorders. The present study aimed to provide a comprehensive overview of the structural diversity of Ulmus phytochemicals, their natural sources, and the chromatographic separation methods used. The pharmacological activities of constituents found in Ulmus were also discussed in detail. Approximately 100 English references, spanning from the 1960s to the present, were identified from electronic resources, primarily using Google Scholar, Web of Science, and ScienceDirect. SciFinder was used to confirm references and chemical structures. “Ulmus”, “phytochemistry”, and “pharmacology” were included as the main keywords to search for articles. A total of 196 natural metabolites were isolated and/or detected. The main classes were the derivatives of flavonoids, monophenols, lignans, neolignans, coumarins, terpenoids, and sterols. Ulmus plants were also found to be rich in polysaccharides and glycoproteins. Crude extracts and isolated compounds possess a variety of pharmacological values, such as anticancer, antioxidant, antimicrobial, anti-inflammatory, antiallergic, antihypertensive, anti-obesity, and topoisomerase inhibitory activities. Ulmus constituents are outstanding agents that offer significant health benefits, including immunomodulatory action and protection of the vascular system, neurons, liver, skin, eyes, excretory system, and hair. Effective separation of the major compounds at elevated concentrations is critically required. Moreover, there is a need to conduct in vivo and clinical trials.

The escalating issue of malaria, including the parasite's resistance to the most effective antimalarial drugs, underscores the significance of discovering a novel antimalarial agent. Extensive research has been conducted on the phytochemicals, including triterpenoids, due to their efficacy in combating malaria. Therefore, in this study, we describe the semisynthesis and characterization of triterpenoids of lupane derivatives by simple modification at the C-3 position, including the evaluation of their efficacy, both in vitro against the Plasmodium falciparum FCR-3 strain and in silico molecular docking simulations targeting the PfATP6 protein. As a result, the structural modification at the C-3 position with 2-furoyl moiety (2b) shows a moderate activity with IC50 = 20.8 ± 0.7 μM, compared to its precursor lupeol (2), which shows a weak activity with IC50 = 122.1 ± 0.3 μM (positive control chloroquine; IC50 = 15.0 ± 0.1 μM). Molecular docking demonstrated a good interaction between 2b and the active site of PfATP6 protein, with a binding energy of - 8.0 ± 0.0 kcal mol^-1. The 2-furoyl ring in 2b shows the binding interaction with the Asn1039 residue via hydrogen bonds. Therefore, compound 2b is identified as a promising candidate as a lead compound for further antiplasmodial studies.

Asymmetric catalysis has witnessed remarkable progress in recent decades, due to the importance of chiral compounds, which play a pivotal role in numerous contemporary fields. Catalytic enantioselective C-C bond formation is an efficient method for constructing a variety of chiral molecules. Copper-catalyzed asymmetric allylic alkylation stands out as one of the most effective and appealing approaches within this category. This review comprehensively summarizes representative examples of asymmetric allylic alkylation catalyzed by copper, involving organometallic reagents over the last few decades, and classifies them according to the type of organometallic reagents, such as organomagnesium and organolithium compounds.