Letters in Organic Chemistry - Volume 23, Issue 1, 2026

Thiazolopyrimidines are heterocyclic analogs of purine bases that are formed from the combination of two heterocycles: thiazole and pyrimidine. This results in the formation of a scaffold shared by both heterocyclic rings, where a nitrogen atom exchanges one carbon atom at the ring junction. Numerous studies have revealed the successful synthesis of various substituted thiazolopyrimidines using a range of synthetic methods, including one-pot multicomponent techniques, microwave irradiation, and environmentally friendly approaches. Extensive research has focused on different thiazolopyrimidine analogs to identify promising compounds with potential therapeutic applications, given their established pharmacological properties. Some novel thiazolopyrimidine derivatives have demonstrated significant activities, including analgesic, anticonvulsant, antiparkinsonian, anti-inflammatory, HIV-1 reverse transcriptase inhibition, anticancer, acetylcholinesterase inhibition, and antiviral effects. It highlights the importance of further exploring the synthesis of novel derivatives within this series, particularly those that may exhibit biological activity. This review provides a comprehensive resource for researchers in the fields of medicinal chemistry and drug discovery, offering valuable insights into the synthetic methodologies and therapeutic potential of thiazolo [3,2-a]pyrimidine derivatives within the timeframe of 1990 to 2025.

α-Cyanostilbene, as a key Aggregation-Induced Emission (AIE) fluorophore, has garnered considerable attention in the fields of biology, chemistry, and materials science for diverse applications. Herein, α-cyanostilbene luminogen with π-electron acceptor-π-electron donor (π-A-π-D) architecture was easily synthesized in a high yield of 86% via Knoevenagel condensation of 4-aminophenylacetonitrile and benzaldehyde in the presence of NaOH. The relationship between the structure and photophysical properties was studied via spectroscopic analysis and Density Functional Theory (DFT) calculations. Interestingly, it demonstrated the solvatochromism in the solution state. With an increasing polarity of the solvent, the Stokes shift was increased, and a significant change in fluorescence from blue to green was observed; however the fluorescence emission intensity decayed due to the Twisted Intramolecular Charge Transfer (TICT) effect. Moreover, it expressed solid green fluorescence and underwent noticeable acidichromism. The periodic HCl/NH3 vapor stimulated changes in fluorescence from green to faint yellow, suggesting that it could be utilized for reusable encryption technology. Furthermore, it displayed apparent fluorescence quenching upon the addition of different amounts of water in hygroscopic organic solvents. The Limits Of Detection (LODs) of it in THF, MeCN, EtOH, and DMF for water detection were 0.0023%, 0.0018%, 0.0015%, and 0.003%, respectively.

Bioethanol production from duckweed (Lemna minor) plants is a promising approach to producing renewable energy. Due to its advantageous characteristics, such as being a non-food feedstock, the fastest-growing angiosperm, globally adaptable to various climates, capable of high starch accumulation under nutrient modifications, and possessing low to no lignin content, Lemna minor is a promising candidate for bioethanol production. This research aimed to produce starch-enhanced Lemna minor under conditions of nutritional starvation. The starch enhancement technique was standardized by performing experiments sequentially with organic manure, nitrogen-free Hoagland media, and full-strength Hoagland media. Initially, the starch quantity was found to be 7%. However, it was observed that during nitrogen stress, high starch accumulation occurred in Lemna minor, and on the 9^th day, it reached its maximum, at 26% with a standard deviation of ±0.3. It was also observed that the protein, glucose, and fructose composition dropped during this experiment. One-way ANOVA analysis was performed for statistical analysis. It was found that during the starch enhancement experiment, the starch level was significantly (P < 0.05) higher in nitrogen-free Hoagland media compared to the organic manure. Therefore, Lemna minor may be used as a substitute for commercial food feedstocks in bioethanol production.

Sustainable green heterocyclic compounds featuring fused bi-, tri-, and tetracyclic systems containing pyrimidine-barbituric acid rings were synthesized via the Hantzsch reaction using a simple and efficient method. The one-pot, three-component reaction involved bis-aldehydes, barbituric acid, and substituted amines, and was carried out under microwave irradiation without the use of a catalyst. The reactions proceeded smoothly, affording the desired products in high yields with straightforward workups. This study emphasizes the importance of green chemistry principles in the synthesis of fused pyrimido[4,5-d]pyrimidine systems, highlighting advantages, such as environmental friendliness, operational simplicity, efficiency, and safety.

Autocatalytic reaction represents an appealing approach in organic chemistry and life sciences. The development of a novel autocatalytic mode for aza-6π electrocyclization reactions represents a promising protocol for the efficient construction of aromatic N-heterocycles. Drawing inspiration from natural biosynthetic pathways for aromatic heterocycles, a wide variety of bioactive natural products can be synthesized efficiently using a biomimetic aza-6π electrocyclization strategy. However, conventional thermal catalysis inevitably suffers from a limited substrate scope and diversity. The photochemical protocol is considered a promising approach in elegant organic synthesis, but the application of photocatalysis in 6π electrocyclization has been rarely explored. In this context, we hypothesized that the aza-hexatriene system of phenanthridine precursor might cyclize with the intermediate imine, which could be formed in situ from the reaction of 2-arylaniline and aldehyde source, respectively. Subsequently, the aza-hexatriene is excited by the corresponding phenanthridine via energy transfer under visible light. The final intramolecular cyclization could generate the substituted phenanthridines. Herein, a novel visible light-induced autocatalytic aza-6π electrocyclization method was reported for the synthesis of diverse phenanthridines. A broad spectrum of 2-arylaniline and (hetero)aryl aldehydes could be well tolerated under metal- and oxidant-free conditions, affording the corresponding phenanthridines in moderate to good yields. This newly developed method represents a highly efficient and cost-effective synthetic protocol. The late-stage functionalization of celecoxib and bromopride derivatives also demonstrated the practical value of this method.

A series of 4-(((8-hydroxyquinolin-7-yl)(phenyl)methyl)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one derivatives (4a–j) were synthesized via a one-pot, three-component reaction. The reaction employed benzaldehyde derivatives (1a–j), 4-aminoantipyrine (2), and 8-hydroxyquinoline (3), using titanium dioxide nanoparticles (TiO2 NPs) as a catalyst. The TiO2 NPs, synthesized through a sol–gel method, efficiently catalyzed the transformation under mild conditions, delivering high yields in just 9 minutes at room temperature. Optimization revealed that 0.010 g of catalyst in methanol was optimal, with protic solvents outperforming aprotic and non-polar ones. The reaction progress was monitored using thin-layer chromatography (TLC), and the final products were isolated via recrystallization. A systematic study of reaction parameters confirmed TiO2 NPs as an efficient, reusable, and environmentally friendly catalyst for multicomponent organic synthesis.