Current Organic Chemistry - Volume 28, Issue 16, 2024

The Friedel-Crafts acylation of natural or unnatural amino acids in stereoretarded manner is willing to prescribed here. Depending on its main skeleton, the typical intra- and intermolecular Friedel-Crafts reaction of amino acids can be differentiated. The unique amino acid's general structure can contribute to the reaction between its carboxyl group and the side chain. Depending on the Friedel-Crafts reaction condition, the amino acid's optical retention can be retarded. This perspective can contribute to the development of this one-century reaction in the field of organic chemistry.

Due to the robust electrophilic properties of the trifluoromethyl group (-CF3), its incorporation into organic compounds can markedly alter their ester affinity, stability, bioavailability, and other properties. The trifluoromethylation reaction is currently experiencing rapid advancement, with an expanding array of substrates and the emergence of novel methodologies. Consequently, compounds containing the -CF3 moiety find extensive utility across diverse fields. This article aims to comprehensively review the latest advancements in trifluoromethylation reaction of olefins, aldehydes, and ketones, encompassing nucleophilic trifluoromethylation, electrophilic trifluoromethylation, and radical trifluoromethylation. The discussion includes an exploration of the types and broadening scope of applicable substrates. Furthermore, this article addresses the associated challenges and delineates prospective directions for future developments in trifluoromethyl reaction.

In terms of fused heterocyclic compounds, pyrrolopyrimidines, and their substituted analogs are among the most extensively explored scaffolds. Based on the location of the nitrogen atom in the pyrrole ring, pyrrolopyrimidines have different isomers. This study deals only with the pyrrolo[2,3-d]pyrimidine isomer. Several techniques are represented and discussed in this review for producing pyrrolo[2,3-d]pyrimidine derivatives. The first one is the cyclization of the pyrimidine ring on the pyrrole ring through the reaction of β-enaminonitrile, β-enaminoester or β-enaminoamide of the pyrrole ring with different bifunctional reagents such as formic acid, acetic acid, acetic anhydride, formamide, isothiocyanate, urea, thiourea, and carbon disulfide. The second technique includes cyclization of the pyrrole ring on the pyrimidine ring via the treatment of pyrimidine, aminopyrimidine, diamino-pyrimidine, or triamino-pyrimidine with different reagents such as nitroalkenes, alkynes, aldehydes, and acid chlorides. In addition, different reaction methodologies like one pot, two-step, and threestep synthetic methodologies were reported. The last technique for producing pyrrolo[2,3-d]pyrimidine derivatives is through miscellaneous reactions. This review also includes the interactions of pyrrolo[2,3- d]pyrimidines at different active centers of the pyrrole ring with different reagents to form N-alkylated, Nglycosylated, C-5, and C-6 adducts. Besides, the interactions on the pyrimidine ring to form chloro, hydrazino, and amino-imino derivatives were also discussed. The amino-imino derivatives are key intermediates for the preparation of tricyclic pyrrolotriazolopyrimidines. Finally, the pharmaceutical and biological properties of some pyrrolo[2,3-d]pyrimidine derivatives have also been mentioned. This information can be utilized to design novel diverse pyrrolopyrimidine derivatives for recent challenges in pharmaceutical and medical studies to develop the already existing drugs or discover new ones.

Three compounds from Andrographis paniculata (Burm. f) Nees leaf were isolated and identified using 1H, 13C, 2D-NMR, and HR-MS techniques for the first time. Compound 3,19-Di-O-acetylandrographolide (3,19-DAA) or (4) is produced by acetylating compound (2). Compounds (2) and (4) have been investigated for their cytotoxic effects on three human cancer cell lines (SK-LU-1, Hela, and HepG2) using the MTT method. Compound (4) demonstrated significant cytotoxicity against all three cancer cell lines, with IC50 values ranging from 8.38 to 10.15 μM. This represents an increase in cytotoxicity of 2.67 to 3.12-fold compared to compound (2). One way to deal with the problem of low water solubility is by encapsulating (4) into liposomes using a thin-film hydration technique. The optimal conditions for maximizing encapsulation efficiency involve molar ratios of phosphatidylcholine, 3,19-DAA, and cholesterol at 4:1:1. Encapsulating compound (4) within nanoscale liposomes increases its water solubility compared to the free form of compound (4). Pose 324 of compound (4) demonstrated the best conformation among 500 docking conformations when docked to enzyme 1T8I in a in silico docking study. The free Gibbs energy and inhibition constant were determined to be -7.09 Kcal/mol and 6.32 μM, respectively. These values help elucidate the strong interaction between compound (4) and the enzyme in the ligand interaction model. The molecular dynamics simulation using Desmond software in the Linux environment was conducted for a duration of 0 to 100 nanoseconds on the complex formed by pose 324 and 1T8I. The results showed effective interactions within the complex, with stability observed from 0 to 60 nanoseconds. Throughout the simulation, specific amino acids such as Ala 499 (involved in 90% of the simulation time with hydrogen bonding via a water bridge) and Thr 501 (involved in 50% of the simulation time with one hydrogen bond via a water bridge) were found to play significant roles. The majority of torsion bondings are C-O bondings in the acetyl group of compound (4), with torsion energy values of 13.47 Kcal/mol. Carbon atom C-29 at position 324 exhibits the highest fluctuation.

2-Thioxoimidazolidin-4-one derivatives 3, 4, 7, 8, and 9 have been synthesized from 3- (benzylideneamino)-2-thioxoimidazolidin-4-one (2) as a starting material. Compounds 3, 4, 7, 8, and 9 were obtained via the reaction of compound (2) with ethyl chloroacetate, methyl acrylate, and chlorophenacyl bromide, respectively. Elemental analysis and several spectroscopy techniques were used to confirm the synthesized compounds. The synthesized compounds, particularly compounds 7 and 8, exhibited significant cytotoxic influences on MCF-7 cells, surpassing staurosporine. Compounds 7 and 8 can induce apoptosis in those treated MCF-7 cells. Studying molecular docking approved that compounds 7 and 8 bind in two and three dimensions to the aromatase binding pockets. Molecular modeling indicates compounds 7 and 8 have a strong affinity for human topoisomerase II beta, establishing its promise as a multifaceted antitumor agent for breast cancer.

Three receptors 1-3, built on adenine, have been synthesized, structurally characterized, and successfully employed for the recognition of monocarboxylic acids. The adenine- based receptors 1-3 have been found to bind monocarboxylic acids via the Hoogsteen (HG) binding site or the Watson-Crick (WC) binding site and form 1:1 complexes in CHCl3. Detailed binding of the receptors 1-3, in the presence of the monocarboxylic acids, corroborates that there is a distinct propensity of the HG site for aromatic carboxylic acids, for example, (S)-mandelic acid and benzoic acid. Aliphatic acids, for example, propanoic acid and rac-lactic acid, on the other hand, prefer to bind at the WC site. The monocarboxylic acid bindings to 1-3 were examined by UV-Vis, fluorescence, and 1H NMR spectroscopic methods, and DFT study.

The reaction of pyridinium chlorochromate (PCC) with furan derivatives gives the corresponding enediones. However, the reaction of pyridinium chlorochromate with furan to give enedione derivatives cannot be performed by using commercial PCC. XRD and XPS analysis of the reagents coupled with DFT calculations can allow us to explain this different behavior. Homemade and commercial PCC have different colors and show some differences in the XRD spectrum. XPS shows the presence of a relevant amount of Cr(III) in the homemade reagent. DFT calculations demonstrate that Cr(III) impurities in the reagent could catalyze the reaction with furan derivatives if an oxygen atom in the Cr(III) derivative attacks the furan ring while it is reoxidized by PCC through the migration of a chlorine atom.