Journal of Heterocyclic Chemistry最新文献

In the current study, we present an efficient and simple method for the synthesis of 1,3-thiazolidin-4-one compounds 4–11 using a one-pot three-component reaction. This process involves the reaction of 3-pyridyl isothiocyanate (1), primary aliphatic or aromatic amines 2a–h, and dimethyl acetylenedicarboxylate (DMAD) in ethanol under ultrasonic conditions. The ultrasonic method for designing 1,3-thiazolidin-4-one compounds is a simple and efficient methodology that produces high-purity products with little effort. It has substantial advantages over traditional methods in terms of cost and energy consumption, making it an efficient and sustainable choice for chemical reactions. One of the main forces behind the creation of new insecticidal substances is the growing resistance to traditional chemical pesticides. In order to overcome this difficulty, scientists are investigating novel pesticide classes with distinct modes of action, so that the novel target synthesized compounds can be screened for insecticidal activities against nymphs and adults of Aphis craccivora.

A key intermediate for the selective 2′-O-glycosylation of biopterin, N²-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (12), was efficiently synthesized via a novel route starting from d-glucose, leading to an improved overall yield. This new pathway involves the preparation of a 5-deoxy-l-arabinose phenylhydrazone derivative (9) as a crucial intermediate in the construction of the pteridine ring. Utilizing compound 12, the first synthesis of microcystbiopterin B (4) was accomplished by glycosylation of 12 with 4,6-di-O-acetyl-2-O-(4-methoxybenzyl)-3-O-methyl-α-d-glucopyranosyl bromide (19) in the presence of silver triflate and tetramethylurea, followed by stepwise deprotection.

A new heterocyclic fused quinoline system namely quinoline fused benzoxepines were obtained in a straight forward sequential one-pot synthesis. The synthetic route includes O-alkylation of 2-(phenyl ethynyl) phenol with 2-chloro-3-(chloromethyl) quinolines and a subsequent intramolecular reductive Heck cyclization. The stereochemistry of the exocyclic double bond at C-6 in target benzoxepines is confirmed as (E)-configuration from single crystal X-ray diffraction. The synthesis is widened to benzazepine analogues by replacing 2-(phenyl ethynyl) phenol with that of N-tosyl/mesyl-2-(phenylethynyl) aniline that is N-alkylation and then cyclisation. Highlights of the devised synthetic plan include readily accessible precursors, easy procedures with wide substrate scope and good yields.

Herein, we report a palladium-catalyzed C-H acetoxylation of N⁹-aryl/benzylpurines by using PhI(OAc)₂ as the stoichiometric oxidant. Despite four interferential nitrogen atoms in the purine skeleton, which all have the ability to participate in metal coordination, we also redirect the C-H activation capacity from the N¹ to the N³ atom using appropriate steric shielding with C⁶-dialkylamino groups. The reaction is scalable to the gram level, demonstrating its effectiveness in late-stage construction of N⁹-substituted purines in pharmaceutical chemistry and synthetic methodology. Meanwhile, the acetoxyl group is a removable group, which can be easily converted to other various valuable groups.

The synthesis of new molecules with potent anticancer activity remains a key objective in medicinal chemistry. A new series of biologically active 2,4-dimethyl-9-aryl-[1,2,4]triazolo[4,3-a][1,8]naphthyridine scaffolds (6a–h) was synthesized and confirmed by the ¹H NMR, ¹³C NMR, and mass spectrometry data. The synthesized derivatives were evaluated for the biological evaluation of anticancer activity against four human cancer cell lines, MCF-7 (breast cancer), Colo-205 (colon cancer), SiHa (cervical cancer), and A549 (lung carcinoma) by using the MTT assay method. All the tested compounds showed significant anticancer activity. Predominantly, two compounds, 6g and 6b, demonstrated the highest anticancer activity with IC₅₀ values of (6b) 6.64 ± 0.44 μM (MCF-7), 9.03 ± 0.36 μM (Colo-205), 10.28 ± 0.25 μM (SiHa), 12.23 ± 1.54 μM (A549), 8.16 ± 0.31 μM (MCF-7), 13.27 ± 0.54 μM (Colo-205), 12.05 ± 0.22 μM (SiHa), 16.07 ± 0.15 μM (A549). Structure–activity relationship (SAR) studies revealed that the presence of electron-donating groups significantly enhanced anticancer activity, whereas electron-withdrawing substituents led to a reduction in potency. Halogen substitutions exhibited moderate anticancer activity.

The direct synthesis of the 2-amino-1,3-thiazole scaffold has been achieved via a three-component reaction between methyl ketones, thioureas, and N-bromosuccinimide, efficiently promoted by 1-(4-sulfobutyl)-3-methylimidazolium hydrogen sulfate among Lewis acidic triflate salts, solid acids, and Brønsted acidic ionic liquids. Under ultrasound assistance, 16 2-amino-1,3-thiazoles were synthesized in yields ranging from 20% to 78% in 35 to 115 min, depending on the substituents of aromatic ketones and thioureas. Additionally, the recovery yield and recycling of 1-(4-sulfobutyl)-3-methylimidazolium hydrogen sulfate were achieved at 82% and five times, respectively, without significantly affecting the yield of 2-amino-4-phenyl-1,3-thiazole.

Recent examples provide clear evidence that ring-chain tautomerism can be exploited successfully in the synthesis of wide varieties of five-membered heterocyclic systems. Owing to the versatile chemotherapeutical activities of azoles, the current review mainly focused on employing the ring-chain tautomeric phenomenon in synthesizing azoles, the five-membered heterocyclic systems having two hetero-atoms such as pyrazoles, isoxazoles, oxazoles, imidazoles, thiazoles. Moreover, we discuss the simultaneous existence of ring-chain tautomerism in two similar or different five-membered heterocycles, which is known as ring-ring tautomerism. Also, the three-, four- and five-component equilibria are reported. In addition, the biological activities of the target azoles are reported.

For the first time, the multicomponent reaction of 3-aminothiophenes with various aldehydes and 1,3-indandione was studied. The unstable starting 3-aminothiophenes were generated in situ from the corresponding sodium salts of 3-aminothiophene-2-carboxylic acids. We have shown that the considered interaction allows us to construct the 9H-indeno[1,2-b]thieno[2,3-e]pyridin-9-one system. A straightforward, one-step approach to a wide range of target polycyclic products was developed based on the presented multicomponent condensation. Using this method, 21 examples of substituted 9H-indeno[1,2-b]thieno[2,3-e]pyridin-9-ones were obtained with yields of up to 76%. The advantages of the designed synthetic route are atom economy, readily accessible starting materials, and a convenient procedure for the isolation of final compounds, avoiding chromatography. The structure of one of the prepared 9H-indeno[1,2-b]thieno[2,3-e]pyridin-9-ones was unambiguously proved using x-ray diffraction.

We report a metal-free, green synthetic route to substituted Aza-anthraquinones that was developed via a multicomponent reaction of aromatic aldehydes, active methylene substrates, and 2-aminonaphthalene-1,4-dione, catalyzed by piperidine in ethanol at 70°C. This atom-economical and regioselective protocol yielded functionalized Aza-anthraquinone hybrids in high yields and Gram-scale quantities, leveraging inexpensive starting materials and demonstrating broad scaffold compatibility. Biological evaluation revealed significant antifungal and antibacterial activities, with several compounds (4b, 4d,4e, 4f, 4g, 4l, and 4b) exhibiting superior inhibition zones compared to standard drugs (Gentamicin and Nystatin). Furthermore, molecular docking studies against the SARS-CoV-2 protein suggested compound 4a as a potential antiviral molecule, displaying a favorable glide score (−5.64 kcal/mol), glide energy (−41.27 kcal/mol), and high bioavailability (89.79%) compared to remdesivir.