Letters in Organic Chemistry - Volume 21, Issue 2, 2024

Tuberculosis is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb), also known as Koch’s bacillus. The involvement of latent forms and resistant strains has aggravated the situation, making the disease a serious public health problem.The objective of the study was to synthesize and evaluate ten new compounds containing camphor nucleus coupled to quinolinic derivatives as probable inhibitors of sensitive and resistant strains of Mtb growth.The synthesis of the final compounds, 3a-e and 4a-e, was based on the use of intermediates previously obtained, in which the coupling of the camphor nucleus to quinoline derivatives was carried out via a convergent route, which resulted in good yields (50-80%). All the final compounds were fully characterized, and the 3-dimensional molecular structure of compound 4c was determined. The antimycobacterial activities of all compounds against Mtb strains were evaluated and the cytotoxicity test was conducted using the in vitro microplate procedure with broth microdilution assay (MTT).Compound 3e was the most active against sensitive and resistant strains, with a minimal inhibitory concentration (MIC) of 9.5 μM similar to ethambutol, a first-line drug used against the tuberculosis. The most active compound 3e was selected for the potential activity against Vero cells and it displayed no cytotoxicity at a concentration near the MIC value.The final compounds were obtained in good yields, with derivative 3e being the most promising with high activity and low cytotoxicity. Such findings open new perspectives for drug development based on the incorporation of camphor nucleus in selected compounds.

An alternative method for the synthesis of 2-heteroaryl or alkynyl benzo[b]thiophene or furan derivatives via direct palladium-catalyzed cross-coupling of 2-benzo[b]thiophene or furan aluminum with heteroaryl or alkynyl bromides, respectively, has been successfully developed. This case is remarkable as the same catalytic system could simultaneously produce either 2-substituted benzo[ b]thiophene or furan derivatives.

Pyrazolo bridged quinolones scaffolds are an important building block in many of the medicinally active new chemical entities. In the current work, synthesis of phenyl-4-(1H-pyrazol-5-yl) conjugated with 1H-pyrazolo[3,4-b]quinolin-5(4H)-ones derivatives has been achieved by one-pot threecomponent reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine 1, 5,5-dimethylcyclohexane-1,3-diones 2, and 1H-pyrazole-5-carbaldehydes 3 using [BMIM]BF4 as green reaction medium with good yields. Furthermore, the synthesized compounds were evaluated for cytotoxic potential towards HeLa and DU145 cells. Of the eight derivatives, compound 4d exhibited good cytotoxicity with an IC50 value of 8.5 and 8.9 μM against DU145 and HeLa cells, respectively. The molecular docking studies revealed that compound 4d displayed good binding energy (-8.4 kcal/mol) against human checkpoint kinase 1.

Heterocyclic compounds and their derivatives epitomize the building blocks of many biological entities, e.g., alkaloids, antibiotics, enzymes, hormones, vitamins, and others that are abundant in nature. The Vilsmeier-Haack reaction has fascinated organic chemists due to its significant use in the synthesis of numerous heterocycles. This analytical evaluation provides a scrutinized overview of the literature on the synthesis of heterocyclic compounds.A comprehensive review of the literature related to Vilsmeier- Haack reagents and reactions is done from PubMed and other sources like google scholar and Google websites.This precise analytic evaluation provides a revolutionary update on the Vilsmeier-Haack reaction and its applications in the synthesis of natural and synthetic compounds.Presently researchers are developing and looking for unconventional reagents that are inexpensive, have high chemical yields, are environmentally benign, recyclable, and robust. The information incorporated in this review paper may inspire more research on the Vilsmeier-Haack reagent and its usage in heterocycle synthesis.

A new pyrrolidinyl-isosteviol bifunctional organocatalyst was synthesized, which was applied to catalyze the asymmetric Michael addition between cyclohexanone and nitroolefins. With 10 mol % of the organocatalyst, the reaction proceeded in water in high yields (up to 99%) with excellent diastereoselectivities (anti/syn up to 98:2) and good enantioselectivities (up to 90% ee). The design of the proline-isosteviol conjugates as organocatalysts was based on the crucial role of proline in the formation of enamine. To sum up, a new pyrrolidinyl-isosteviol bifunctional organocatalyst was synthesized, which could effectively catalyze the C-C formation reaction between a number of nitroolefins and cyclohexanone.

This study investigates the use of ionic liquids (ILs) immobilized on HT-clay as catalysts for the Baylis-Hillman reaction. The catalytic system comprised three different types of ILs ([HIM]Im, [BIM]Im, [EIM]Im) and exhibited high reactivity, and the B-H products were obtained in good yield, which is superior to previously reported catalytic systems, whether they were heterogeneous or homogeneous. The HT-clay immobilized with ILs also allowed for easy recovery from the reaction mass and could be recycled for up to 7 consecutive runs with only a slight decrease in activity. Moreover, the scope of our catalytic system was extended to synthesize biologically active lactone ceramide analogs using the Baylis-Hillman reaction at room temperature with (S-) Garner aldehyde and methyl acrylate. The synthesis was successful, and we obtained good yields of the desired products, highlighting the versatility of the ionic liquid immobilized HT-clay catalytic system. This study demonstrates the potential of ionic liquid immobilized HT-clay as a promising catalyst for various organic reactions. Our findings emphasize the importance of developing efficient and environmentally friendly methods for synthesizing valuable organic compounds. The results obtained from this study provide a significant contribution to the ongoing research in the field of catalysis and will be useful for developing new approaches to the synthesis of complex organic molecules.

This study deals with the density functional theory calculations of eco-friendly designed nonionic sugar-based surfactants (SurfRing and SurfLinear). Then, it compares the results with the structural and electronic properties of a fatty alcohol surfactant (SurfFA). All geometry optimizations and energy calculations were performed using M06-2X functional and 6-31G(d,p) basis sets. The quantum chemistry reactivity parameters showed the effect of hydrophilic fragment structure on intramolecular interactions and conformational stability of surfactants. The results showed that SurfRing is more reactive than SurfFA. Based on Bader’s quantum theory of atoms in molecules (QTAIM), one intramolecular hydrogen bond (O43…H67128;•O57, EHB: -11.9 kcal.mol^-1) is characterized for SurfRing, while two hydrogen bond interactions (O63…H60128;•O59 and O65…H64128;•O63 with EHB of -13.0, and -12.3 kcal.mol^-1, respectively) form between the hydroxyl groups of SurfLinear. These intramolecular hydrogen bonds are partially covalent interactions. Natural bond orbital analysis reveals that the most prominent interaction energy is electron donation from the oxygen atom lone pair to the antibonding orbital of the O128;•H bond supporting the results obtained from the AIM calculations.

Isatin-derivatives are an important class of nitrogen-containing heterocyclic compounds in organic synthesis. On the other hand, 1,3-thiazoles are 5-membered heterocyclic compounds containing nitrogen and sulphur atoms. Hydrazinyl thiazoles are often prepared through the classical condensation of aldehydes or ketones with thiosemicarbazide to yield thiosemicarbazones, which will then undergo heterocyclization with phenylacyl bromides to give the corresponding hydrazinyl thiazoles. Nowadays, multi-component reactions (MCRs) are considered the most powerful tool in organic synthesis. The use of water as a green solvent in organic synthesis is one of the goals of green chemistry. In this study, a series of new hydrazinyl thiazoles 3a-3u bearing an isatin moiety were synthesized in good yield via a one-pot three-component condensation reaction of isatins with thiosemicarbazide and phenyl acyl bromides in water under reflux condition. All the synthesized compounds were characterized by IR, 1D-NMR, 2D-NMR and LC/MS spectral data.

In literature, dimethyl sulfoxide (DMSO) catalyzed bromination of arenes and heteroarenes is reported. In this study, simple, mild, and chemoselective N-bromosuccinimide (NBS) mediated monobromination of arenes and heteroarenes using butadiene sulfone as a catalyst is reported.Butadiene sulfone is a good substitute for DMSO as it is volatile, easy to recover and recycle, and environment- friendly. The method has been demonstrated to give high-yield brominated products for an extensive range of activated and deactivated arenes.

Utilization of α,α-dihalocarbonyl compounds as synthetic equivalents to α-halocarbonyl compounds has been explored in the synthesis of a wide range of highly useful heterocycles and α- functionalized ketones. The continuously growing demand of α,α-dibromoketones, as highly reactive and mild synthetic precursors/intermediates, to carry out selective organic transformations, prompted us to investigate their potential application for the synthesis of thiazolo[3,2-a]benzimidazoles. In this study, a remarkable application of α,α-dibromoacetophenones 5a-g in the development of a facile protocol for the synthesis of thiazolo[3,2-a]benzimidazoles 4a-g by avoiding the use of lachrymatory α-haloketones is described. Although the mechanism for the debromination from the intermediate compound 6 under these conditions is not confirmed, possible pathways have been suggested.

1,3-dimethyl-4,5-diaminouracil has been used as an efficient protecting group for the carbonyl moiety in sugars by the formation of the imine group. The protection reaction is carried out under mild conditions, the yields are quantitative in most of the cases, and the protecting group is completely recovered and reused. After per-acetylation, deprotection is accomplished at room temperature with aqueous formic acid to produce acyclic acetylated sugars in good global yield.