Current Organic Chemistry - Volume 25, Issue 7, 2021

Cancer is the second leading cause of death in Iran, next to heart disease. Current therapy suffers from the major limitations of side effects and drug resistance, so the characterization of new structures that can be power-selective and less-toxic anticancer agents is the main challenge to medicinal chemistry research. Furoxan (1,2,5-oxadiazole-2-oxide) is a crucial compound with many medicinal and pharmaceutical properties. The most important aspect of furoxan is the nitric oxide (NO) molecule. One of the most essential furoxan derivatives, which could be utilized in medicinal goals and pharmaceutical affairs, is benzofuroxan. Furoxan could be described as a NO-donating compound in a variety of reactions, which could also appear as hybridised with different medicinal compounds. This review article presents a summary of syntheses and antitumor properties of furoxan derivatives as possible chemotherapy agents for cancer. Furoxan can inhibit tumor growth in vivo without any side effects in normal cells. Furthermore, due to NO-releasing in high levels in vivo and a wide range of anticancer compounds, furoxan derivatives and especially its hybridised compounds could be considered as antitumor, cytotoxic and apoptosis compounds to be applied in the human body.

The role of oxindole derivatives is discussed as starting materials in diverse organic reactions, including two and more components, between the years 2014 until 2020. Oxindoles are famous because of their biological properties. For instance, chromanone-fused polycyclic pyrrolidinyl-dispirooxindoles, functionalized polycyclic spiro-fused carbocyclicoxindole, and 3,3-disubstituted oxindoles have anti-cancer, anti-tumor, and anti-microbial properties, respectively. Therefore, various methods for synthesizing the oxindole structures have received much attention in organic chemistry.

Over the years, the branch of oncology has reached a mature stage, and substantial development and advancement have been achieved in this dimension of medical science. The synthesis and isolation of numerous novel anticancer agents of natural and synthetic origins have been reported. Thiazole and 4-thiazolidinone containing heterocyclic compounds, having a broad spectrum of pharmaceutical activities, represent a significant class of medicinal chemistry. Thiazole and 4-thiazolidinone are five-membered unique heterocyclic motifs containing S and N atoms as an essential core scaffold and have commendable medicinal significance. Thiazoles and 4-thiazolidinones containing heterocyclic compounds are used as building blocks for the next generation of pharmaceuticals. Thiazole precursors have been frequently used due to their capabilities to bind to numerous cancer-specific protein targets. Suitably, thiazole motifs have a biological suit via inhibition of different signaling pathways involved in cancer causes. The scientific community has always tried to synthesize novel thiazole-based heterocycles by carrying out different replacements of functional groups or skeleton around thiazole moiety. Herein, we report the current trend of research and development in anticancer activities of thiazoles and 4-thiazolidinones containing scaffolds. In the current study, we have also highlighted some other significant biological properties of thiazole, novel protocols of synthesis for the synthesis of the new candidates, along with a significant broad spectrum of the anticancer activities of thiazole containing scaffolds. This study facilitates the development of novel thiazole and 4-thiazolidinone containing candidates with potent, efficient anticancer activity and less cytotoxic property.

In the microwave-assisted alcoholysis of dialkyl phenylphosphonates performed in the presence of suitable ionic liquids, such as [bmim][BF4] or [bmim][PF6], affording the phosphonate with mixed alkoxy groups and the fully transesterified product, the fission of the phosphonate function to the ester-acid or diacid moiety was inevitable. Moreover, in the presence of [emim][HSO4], the reaction could be performed to afford the phosphonic esteracid with a selectivity of 66% and the diacid with a selectivity of 97%. The ester-acids provided by the new protocol may be valuable intermediates.

A novel, fast, and straightforward procedure for the synthesis of di- and trifunctionalized isoxazoles starting from 2-ethoxymethylenemalononitrile with different ratios of hydroxylamine in the presence of sodium acetate is described in this paper. The current method’s features include the availability of the starting materials, moderate reaction conditions, and the simplicity of the workup. The structures are characterized using different spectroscopic studies, such as infrared (IR), ¹H/¹³C nuclear magnetic resonance (NMR), and elemental analysis, in addition to X-ray single-crystal determination. The gauge-invariant atomic orbital (GIAO) ¹H and ¹³C NMR chemical shift values of 5-aminoisoxazole-4-carbonitrile and 3,5-diaminoisoxazole-4-carboxamide are calculated in the ground state using the density functional theory (DFT) with the 6-311+G(d, p) basis set and are compared with the experimental data, in addition to the calculation of the molecular electrostatic potential (MEP) distribution, and the frontier molecular orbitals (FMOs) for the synthesized isoxazoles are illustrated theoretically.