Fe₃O₄‐supported sulfonated graphene oxide as a green and magnetically separable nanocatalyst for synthesis of 2-amino-3-cyano-4<i>H-</i>chromene derivatives and their in-silico studies

Under ultrasound irradiation, 17 examples of 2-Amino-3-cyano-4H-chromene derivatives were prepared via one-pot three components domino Knoevenagel–Michael condensation reaction of aliphatic/aromatic/heterocyclic aldehydes, malononitrile, and α-naphthol/β–naphthol/resorcinol in the presence of Fe3O4‐supported sulfonated graphene oxide as a green and magnetically separable nanocatalyst in H2O: EtOH (1:1) solvent system. FT-IR, TGA, SEM, and XRD were used to evaluate the catalyst. The current protocol is appealing because of high atom economy (95%), excellent yields (88-95%), its short reaction time, waste-free conditions, cost-effectiveness, use of a nontoxic solvent, lack of high temperature for reflux, non-chromatographic purification of products, recyclability of catalyst, etc. In-silico studies were conducted on the selected proteins DNA gyrase (1KZN) and CYP51 (4WMZ) to study the docking interactions with highest docking scores 4h (−8.8 kcal/mol) and 4e (−10.1 kcal/mol), respectively. ADME and Toxicity analysis of docked compounds and reference drugs were also done.HighlightsRoom temperature and ultrasound assisted three-component synthesisSynthesis of biological important 4H-chromene derivatives in H2O: EtOH (1:1) solventHigh yields of products (88–95%) within rapid reaction time (10–15 min).High atom economy 95%.Avoid of column chromatographyIn-silico studiesEasy and fast work upMagnetically separable and reusable catalyst. Room temperature and ultrasound assisted three-component synthesis Synthesis of biological important 4H-chromene derivatives in H2O: EtOH (1:1) solvent High yields of products (88–95%) within rapid reaction time (10–15 min). High atom economy 95%. Avoid of column chromatography In-silico studies Easy and fast work up Magnetically separable and reusable catalyst. </p

Electrochemical Post-Ugi Cyclization for the Synthesis of Highly Functionalized Spirolactams

The combination of the Ugi reaction and electro-organic synthesis can aid in the creation of novel heterocycles that have not been previously explored. In this study, a new strategy utilizing bis-amides from the Ugi reaction has been developed, which can produce C–S, C–Se, and C–CO functionalized five-membered spirolactams mediated by electricity under catalyst- and metal-free conditions. Notably, this approach can be applied using a microelectro-flow reactor (μ-EFR) for gram-scale synthesis. The described strategy can synthesize complex azaspiro-fused tricyclic scaffolds with high diastereo- and regioselectivity, highlighting its versatility and potential

New Orally Active Amino- and Hydroxy-Functionalized 11-Azaartemisinins and Their Derivatives with High Order of Antimalarial Activity against Multidrug-Resistant <i>Plasmodium yoelii</i> in Swiss Mice

By use of artemisinin <b>1</b> as the starting material, two new amino- and hydroxy-functionalized 11-azaartemisinins <b>9</b> and <b>11</b> and their derivatives <b>12a</b>–<b>g</b>, <b>13a</b>–<b>g</b>, <b>14a</b>–<b>g</b>, and <b>15a</b>–<b>c</b> have been prepared and screened for antimalarial activity by oral route against multidrug-resistant <i>Plasmodium yoelii</i> in Swiss mice. While azaartemisinins <b>9</b> and <b>11</b> showed only modest activity, several of their derivatives showed high order of antimalarial activity. Biphenyl-based compound <b>13f</b>, the most active compound of the series, provided 100% and 80% protection to the infected mice at 12 mg/kg × 4 days and 6 mg/kg × 4 days, respectively. Compounds <b>12f</b>, <b>13b</b>, <b>13e</b>, <b>13g</b>, and <b>14f</b> showed 100% protection at 12 mg/kg × 4 days, while compounds <b>12a</b>–<b>c</b>, <b>14a</b>, <b>14c</b>–<b>e</b>, <b>14g</b>, and <b>15a</b>–<b>c</b> showed similar levels of protection at 24 mg/kg × 4 days. Clinically useful drug β-arteether provided 100% protection at 48 mg/kg × 4 days and 20% protection at 24 mg/kg × 4 days in this model

Bile Acid-Based 1,2,4-Trioxanes: Synthesis and Antimalarial Assessment

A new series of bile acid-based trioxanes <b>23a</b>–<b>d</b>, <b>24a</b>–<b>d</b>, <b>25a</b>–<b>d</b>, <b>26a</b>, <b>26b</b>, and <b>26d</b> have been synthesized and assessed for their antimalarial activity against multidrug-resistant Plasmodium yoelii in Swiss mice by oral route. The antimalarial activity of these trioxanes showed a strong dependence on the side-chain length; shortening side-chain length lead to increase in activity. The antimalarial activity also showed even stronger dependence on the stereochemistry at C3 and C6 (C21 in Figure ) of the trioxane moiety. Of the two diastereomers isolated of each of the trioxanes, more polar one was significantly more active than the less polar one. The more polar diastereomer of the trioxanes <b>26a</b>, <b>26b</b>, and <b>26d</b>, were the most active compounds of the series. All these three trioxanes provided 100% protection at 24 mg/kg × 4 days. In this model β-arteether provided 100% and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively

Catalyst-Controlled Structural Divergence: Selective Intramolecular 7-<i>endo</i>-<i>dig</i> and 6-<i>exo</i>-<i>dig</i> Post-Ugi Cyclization for the Synthesis of Benzoxazepinones and Benzoxazinones

Metal catalyzed post-Ugi cyclization of bis-amides is reported in this study. Exposure of bis-amides to Pd­(II) catalyst triggered the formation of seven-membered benzoxazepinones. This investigation established that changing the catalyst to a Echavarren’s gold­(I) turned off cyclization to seven member ring and turned on 6-<i>exo</i>-<i>dig</i> annulations to afford family of six-membered benzoxazinones. To support the proposed mechanisms, quantum chemical based density functional theory calculations have been performed and validated. This novel method obtained molecular complexity up to four modular inputs and divergence of two different skeletons. 2D NMR spectroscopic techniques and single crystal X-ray diffraction established the proposed structures