Substituted Diaziridines via [2 + 1] Annulation of Dialkyl Azodicarboxylates with Diazo Esters and Pyridinium Ylides.

Herein, we report the [2 + 1] annulation reactions of dialkyl azodicarboxylate with various diazoesters and generated pyridinium ylides, resulting in the formation of substituted diaziridines in high yields. Notably, these reactions are conducted without any acids, bases, metal catalysts, or photosensitizers, demonstrating a robust strategy for synthesizing structurally diverse diaziridines. Furthermore, the diaziridines can be treated with a variety of arenes, natural products, and pharmaceutical compounds, yielding a range of substituted hydrazine conjugates.

Photolytic -Selective Amino Pyridylation of Aryl Isocyanates with -Amino Pyridinium Ylides for the Synthesis of -Arylsulfonyl Ureas.

Herein, we report an expedient synthesis of aryl sulfonyl ureas and from -amino pyridinium ylides and aryl isocyanates. -Aminopyridinium ylides are synthesized via blue light-emitting diode irradiation of pyridine/isoquinoline and appropriate iminoiodinanes. The strategy involved a hitherto unknown carboamination of imine moieties (of aryl isocyanates) via a three-component reaction of pyridine derivatives/isoquinoline , -aryl sulfonyl iminoiodinanes , and numerous aryl isocyanates at room temperature in 2-methyl tetrahydrofuran to afford the target compounds in moderate to excellent yields.

Novel Autotaxin Inhibitor ATX-1d Significantly Enhances Potency of Paclitaxel-An In Silico and In Vitro Study.

The development of drug resistance in cancer cells poses a significant challenge for treatment, with nearly 90% of cancer-related deaths attributed to it. Over 50% of ovarian cancer patients and 30-40% of breast cancer patients exhibit resistance to therapies such as Taxol. Previous literature has shown that cytotoxic cancer therapies and ionizing radiation damage tumors, prompting cancer cells to exploit the autotaxin (ATX)-lysophosphatidic acid (LPA)-lysophosphatidic acid receptor (LPAR) signaling axis to enhance survival pathways, thus reducing treatment efficacy.

Unveiling Alternate Electrode Electrolysis in Electro-Photochemical and Electro-Organic Syntheses.

Electro-photochemical organic synthesis is a rapidly growing field. Recently, technological advancement has contributed significantly to improve electro- and photolytic organic transformations in terms of energy efficiency and productivity. Herein, we have introduced alternating electrode electrolysis|alternate electrode electrolysis (AEE), a new technique in electrosynthesis which in combination with blue LED demonstrated an interesting three-component reaction with aryl diazoesters, 1,4-quinones, and acetone to synthesize ketal-functionalized 1,4-quinones.

Long ties accelerate noisy threshold-based contagions.

In widely used models of biological contagion, interventions that randomly rewire edges (generally making them 'longer') accelerate spread. However, recent work has argued that highly clustered, rather than random, networks facilitate the spread of threshold-based contagions, such as those motivated by myopic best response for adoption of new innovations, norms and products in games of strategic complement. Here we show that minor modifications to this model reverse this result, thereby harmonizing qualitative facts about how network structure affects contagion.

Light-Induced Generation and Cycloaddition Reactions of Benzyne: Synthesis of Naphthoxindoles E and Annulated Indolizines.

By virtue of their high electrophilic nature, benzynes serve as reactive dienophiles in numerous cycloaddition reactions. However, in situ generation of benzyne involves either base-mediated thermal reactions, low-temperature conditions, or metal-catalyzed reactions of substituted arenes. This limits the applicability of benzynes as suitable dipolarophiles in cycloaddition reactions.

Protocol for aqueous synthesis of bioactive quaternary ammonium betaine derivatives under blue LED.

Quaternary ammonium compounds exhibit diverse applications as antibiotics, as surfactants, in paper industries, in sewage treatment, and in aquaculture. Here, we present a protocol for synthesizing a library of bioactive quaternary ammonium betaine derivatives under blue LED in water. We describe steps for preparing diazo compounds, synthesizing glycine betaine derivatives, and isolating pure final compounds via precipitation from an aqueous reaction mixture.

Synthesis and Anti-Melanoma Activity of Acryloyl Pyridinone Analogues.

A major challenge for clinical management of melanoma is the prevention and treatment of metastatic disease. Drug discovery efforts over the last 10 years have resulted in several drugs that improve the prognosis of metastatic melanoma; however, most patients develop early resistance to these treatments. We designed and synthesized, through a concise synthetic strategy, a series of hybrid olefin-pyridinone compounds that consist of structural motifs from tamoxifen and ilicicolin H.

Photoinduced [3+2] Cycloaddition of Carbenes and Nitriles: A Versatile Approach to Oxazole Synthesis.

We have developed a photoinduced protocol for the synthesis of pharmaceutically important oxazole molecules using diazo- and nitrile-containing reactants. The process involves the initial photolysis of the diazo compound to afford singlet carbenes, which are tapped by nitriles in a [3+2] cycloaddition fashion to give substituted oxazoles. With di-nitrile compounds, useful bis-oxazoles were obtained.

Metal-free synthesis and study of glycine betaine derivatives in water for antimicrobial and anticancer applications.

A sustainable synthesis of interesting glycine betaine derivatives from cyclic 3°-amines viz. N-methyl morpholine (), N-methyl piperidine (), and 1,4-diazabicyclo[2.2.

Metal-free synthesis of -sulfonyl imines from benzyl alcohol derivatives and iminoiodinanes mechanochemistry.

An expedient and operationally convenient mechanochemical synthesis of aryl/heteroaryl -sulfonyl imines is reported by reacting iminoiodinanes with numerous aryl/heteroaryl benzyl alcohols in ball milling apparatus (RETSCH 400™) with three 5 mm stainless steel (ss) balls in a 5 mL stainless steel (ss) reaction jar. CHCl ( = 0.2-0.

Unveiling catalyst-free electro-photochemical reactivity of aryl diazoesters and facile synthesis of oxazoles, imide-fused pyrroles and tetrahydro-epoxy-pyridines carbene radical anions.

Herein, we report a reagent-less (devoid of catalyst, supporting electrolyte, oxidant and reductant) electro-photochemical (EPC) reaction [electricity (50 μA) and blue LED (5 W)] of aryl diazoesters to generate radical anions which are subsequently reacted with acetonitrile or propionitrile and maleimides to generate diversely substituted oxazoles, diastereo-selective imide-fused pyrroles and tetrahydroepoxy-pyridines in good to excellent yield. Thorough mechanistic investigation including a 'biphasic e-cell' experiment supports the reaction mechanism involving a carbene radical anion. The tetrahydroepoxy-pyridines could be fluently converted to fused pyridines resembling vitamin B derivatives.

Blue LED Induced Three Component Reactions for the Generation of 4,6-Dioxo-hexahydro-1H-furo[3, 4-c] pyrrole: Their Evaluation as Anticancer Agents through PARP-1 Inhibition.

Herein we report a catalyst, metal and additive free generation of carbonyl ylides by blue LED irradiation of aryl diazoacetates in presence of aldehydes. The resulting ylides underwent [3+2] cycloaddition with substituted maleimides present in the reaction mixture to afford 4, 6-dioxo-hexahydro-1H-furo[3, 4-c] pyrrole in excellent yields. Fifty compounds were synthesized based on this scaffold.

Light induced diversity-oriented synthesis (DOS) library of annulated indolizine fluorophores for imaging non-lysosomal lipid droplets (LDs).

We report the design, synthesis, and biological evaluation of a novel class of annulated indolizines as fluorescent probes. The compounds were generated through an eco-friendly, blue LED-induced domino reaction in ethyl acetate. A library of 24 coloured compounds exhibited tuneable emissions.

Development of indolealkylamine derivatives as potential multi-target agents for COVID-19 treatment.

COVID-19 is a complex disease with short-term and long-term respiratory, inflammatory and neurological symptoms that are triggered by the infection with SARS-CoV-2. As many drugs targeting single targets showed only limited effectiveness against COVID-19, here, we aimed to explore a multi-target strategy. We synthesized a focused compound library based on C2-substituted indolealkylamines (tryptamines and 5-hydroxytryptamines) with activity for three potential COVID-19-related proteins, namely melatonin receptors, calmodulin and human angiotensin converting enzyme 2 (hACE2).

"All-Aqueous" Tandem Boc-Deprotection and Alkylation of N-Bocbenzimidazole Derivatives under Visible Light with Alkyl Aryl Diazoacetates: Application to Site-Selective Insertion of Carbenes into the N-H Bond of Purines.

Herein, we have reported a blue LED-induced tandem Boc-deprotection and NH-alkylation of benzimidazole derivatives with methyl aryl diazoacetates. The reactions occur in water at room temperature. The desired products are obtained in good to excellent yields.

Blue Light-Emitting Diode-Induced Direct C-H Functionalization of 1,4-Quinones with Aryl and Alkyl Boronic Acids.

A direct functionalization of numerous 1,4-quinones with various aryl boronic acids is reported under blue light-emitting diodes (LEDs). This reaction occurs at room temperature in an open flask without any catalysts, base, and oxidants in acetonitrile (ACN) and is scalable in grams. With diverse 1,4-quinones like 1,4-benzo-, naphtho-, anthra-, and 4-bromonaphthoquinones as substrates, facile cross coupling reactions occur with aryl and alkyl boronic acids without assistance from any photocatalysts.

Cu(II)-Catalyzed Multicomponent Reaction of Pyridine Derivatives/Isoquinolines with Iodonium Ylide and 1,4-Quinones Using Mechanochemistry.

An efficient copper-catalyzed solvent-free multicomponent reaction for pyridine derivatives, iodonium ylides, and 1,4-quinones is developed a room-temperature ball milling technique. The reported protocol provides a sustainable synthesis of isoindolo[2,1-a]pyridine/isoquinoline class of molecules in good to excellent yield in a mixer mill (RETSCH MM400) engaging the commercially available copper acetate (Cu(OAc)) as a catalyst without the use of organic solvents. It tolerates a myriad of electron-rich and electron-deficient functionalities on the pyridine moiety.

Capturing a Pentacyclic Fragment-Based Library Derived from Perophoramidine: Their Design, Synthesis and Evaluation as Anticancer Compounds by DNA Double-Strand Breaks (DSB) and PARP-1 Inhibition.

Herein we have reported the discovery of a pentacyclic building block comprised of fused indole-quinoline and piperidinone from the natural product perophoramidine as a formidable anticancer agent. The compounds were synthesized in six steps where the key steps involved a blue LED mediated intramolecular cyclopropanation of the indole intermediates and concomitant reduction of the associated aryl nitro moiety to nitroso in the molecule. Cytotoxicity screening of the compounds against an array of cancer cells that is, MCF7, HCT116 and A549 demonstrated 0.

Tuning Potency of Bioactive Molecules via Polymorphic Modifications: A Case Study.

Polymorphism in drugs and bioactive molecules is not uncommon, and it has remained as one of the critical issues in drug development processes. While improving physicochemical properties of bioactive molecules has been a prime focus of the pharmaceutical chemists, not much efforts have been put toward the improvement of their potency via polymorphic modifications. Here, we consider five cases of 5-arylidene-2-aminothiazolidinones derivatives, the known anticancer agents, and discover eights polymorphs in three out of the five cases.

A sustainable C-H functionalization of indoles, pyrroles and furans under a blue LED with iodonium ylides.

Pyrrole and indole derivatives are functionalized a green initiative with the dimethyl malonate derived phenyl iodonium ylide 4a in the presence of a blue LED C-H functionalization of the respective heterocycles in methanol to generate the desired compounds 5-7 in moderate to good yields. Control experiments provide insight into the probable reaction mechanism. Finally, the strategy is successfully applied in the generation of azepino[4,5-]indole 12a/b.

Blue Light-Emitting Diode-Mediated Generation of Pyridinium and Isoquinolinium Ylides from Aryl Diazoesters: Their Application in the Synthesis of Diverse Dihydroindolizine.

Blue light-emitting diode-mediated environmentally sustainable three component reactions among pyridine/isoquinoline , aryl diazoesters , and acrylic ester/3-alkenyl oxindoles provide various dihydroindolizines to in excellent yield. The principle of the strategy is photolytic generation of nitrogen ylides from N-heteroarenes and aryl diazoesters and their subsequent [3 + 2] cycloaddition reaction with dipolarophiles. Detailed mechanistic analysis of the transformation through control experiments establishes this strategy as the foundation for the photolytic multicomponent reaction.

Developing C2-Aroyl Indoles as Novel Inhibitors of IDO1 and Understanding Their Mechanism of Inhibition Mass Spectroscopy, QM/MM Calculations and Molecular Dynamics Simulation.

Indoleamine-2,3-dioxygenase (IDO1) and tryptophan dioxygenases are two heme based metalloenzymes that catalyze the tryptophan oxidation reaction by inserting molecular dioxygen to cleave the pyrrole ring. The mechanism of such ring cleavage reaction is of carcinogenic importance as the malignant tumors recruit this mechanism for immune invasion. In the presence study, we have synthesized a Novel C2 aroyl indoles inhibitor, which shows significant inhibition of 180 nM at IC scale.

Orthogonal Syntheses of γ-Carbolinone and Spiro[pyrrolidinone-3,3']indole Derivatives in One Pot through Reaction Telescoping.

Herein we report a series of telescoping methodologies for one pot synthesis of biologically relevant γ-carboline derivatives and spiro[pyrrolidinone-3,3']indole . Initially the three consecutive steps of cyclopropanation, phthalimide deprotection, and Boc-deprotection have been congregated in a single reaction vessel to afford a ∼1:1 mixture of and . Next, careful optimization of the reaction sequence and the conditions generated an orthogonal approach to access compounds and exclusively.

Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum.

Background: Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment.

Methods: The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.