Targeted Activation in Localized Protein Environments via Deep Red Photoredox Catalysis

State-of-the art photoactivation strategies in chemical biology provide spatiotemporal control and visualization of biological processes. However, using high energy light (λ < 500 nm) for substrate or photocatalyst sensitization can lead to background activation of photoactive small molecule probes and reduce its efficacy in complex biological environments. Here we describe the development of targeted aryl azide activation via deep red light (λ = 660 nm) photoredox catalysis and its use in photocatalyzed proximity labeling. We demonstrate that aryl azides are converted to triplet nitrenes via a novel redox-centric mechanism and show that its spatially localized-formation requires both red light and a photocatalyst-targeting modality. This technology was applied in different colon cancer cell systems for targeted protein environment labeling of epithelial cell adhesion molecule (EpCAM). We identified a small subset of proteins with previously known and unknown association to EpCAM, including CDH3, a clinically relevant protein that shares high tumor selective expression with EpCAM.

Organocatalytic synthesis and antitumor activity of novel 1,2,3-triazoles derived from fatty β-ketoesters

Background: Developing methods to synthesize highly functionalized and complex 1,2,3-triazoles from various combinations of substrates remains a significant challenge in organic synthesis. Thus, to the best of our knowledge, an organocatalytic approach to synthesize 1,2,3-triazoles derived from fatty acids has not been explored. Objective: In this sense, we describe here the organocatalyzed synthesis and preliminary results of antitumor and cytotoxic activity of a range of 1,2,3-triazoles derived from fatty esters. Methods: To synthesize 1,2,3-triazoles 3 derived from fatty β-ketoesters, we performed the reaction of appropriate aryl azides 2a-j with β-ketoesters 1a-c in the presence of 5 mol% of DBU using DMSO as a solvent at 70 °C for 24 h. The viability of 5637 cells was determined by measuring the reduction of soluble MTT to water-insoluble formazan. The IC50 concentration that inhibits 50% of cell growth and the results were obtained by at least three independent experiments in triplicate for each test. Results: Through enolate-mediated organocatalysis, 1,2,3-triazoles 3 derived from fatty β-ketoesters were synthesized in moderate to excellent yields by reacting fatty esters 1 with aryl azides 2 in the presence of a catalytic amount of 1,8-diazabicyclo[5.4.0]undec-7-ene (5 mol%). All compounds derived from palmitic acetoacetate 1a were evaluated regarding induced cytotoxicity in vitro in a human bladder cancer cell line, and compounds 3a, 3d, 3e, and 3g were shown to be promising alternatives for bladder cancer treatment and presented the lowest inhibitory concentration of IC50. Conclusion: We described a synthetic procedure to prepare 1,2,3-triazoles derived from fatty β-ketoesters by DBU-catalyzed 1,3-dipolar cycloaddition reactions of fatty esters with different aryl azides. Compounds derived from palmitic acetoacetate were screened for antitumor and cytotoxic activity in vitro in human bladder cancer cell lines, and compounds 3a, 3d, 3e, and 3g showed potential to treat bladder cancer.

Azidation of aryl halides promoted by EDTA

An efficient approach to azidation of aryl halides is described here. Good yields of aryl azides were obtained with [CuI/EDTA]–3 as a catalytic system. Cost-affectivity of the EDTA compared to expensive DMEDA (1 : 500 times) along with the use of 7EtOH:3H2O as mixed solvent and green medium makes it to be a suitable method for selective synthesis of aryl azides.

Synthesis and Antitumor Activity of 1-Substituted 1,2,3-Triazole-Mollugin Derivatives

A new series of mollugin-1,2,3-triazole derivatives were synthesized using a copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of corresponding O-propargylated mollugin with aryl azides. All the compounds were evaluated for their cytotoxicity on five human cancer cell lines (HL-60, A549, SMMC-7721, SW480, and MCF-7) using MTS assays. Among the synthesized series, most of them showed cytotoxicity and most of all, compounds 14 and 17 exhibited significant cytotoxicity of all five cancer cell lines.

Visible-Light-Driven photocyclization reaction: Photocatalyst-free mediated intramolecular N-N coupling for synthesis of 2H-indazole-3-carboxamides from aryl azides

In this report, the visible-light-driven photocyclization reaction of aryl azides to access 2H-indazole-3-carboxamides in moderate to excellent yields has been realized efficiently under photocatalyst-free and external additive-free conditions. N-N bond...

Fluoro Aryl Azides: Synthesis, Reactions and Applications

Background: The complex photochemistry of aryl azides has fascinated scientists for several decades. Spectroscopists have investigated the intermediates formed by different analytical techniques. Theoretical chemists have explained the intrinsic interplay of intermediates under different experimental conditions. Objective & Method: A complete understanding of the photochemistry of a given fluoro aryl azide is a basic requisite for its use in chemistry. In this review, we will discuss the synthesis of several fluoro substituted aryl azides and the reactions and intermediates generated upon photolysis and thermolysis of these azides and some examples of their applications in photoaffinity labeling and organic synthesis. Conclusion: In spite of the extensive research on the photochemistry of fluoro aryl azides, there are some areas that remain to be investigated. The application of this reaction in the synthesis of novel heterocyclic compounds has not been fully studied. Since fluorophenyl azides are known to undergo C-H and N-H insertion reactions, they could be used to prepare new fluorinated molecules or in the biochemical process known as photoaffinity labeling.

A Facile, Efficient step-wise and Alternative Synthesis of Indolyl triazoles via “Click” Chemistry

: A series of new 1,2,3 triazoles hybrids were synthesized using a Cu-catalysed azide-alkyne cycloaddition reaction. Thus, a remarkable rapid click reaction of aryl azides with terminal alkynes at room temperature in DMF afforded new 4-((1-((1-(4-methoxy-3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-indol-3-yl)methylene)-3-methyl-1-phenyl-1Hpyrazol-5(4H)-ones in good to excellent yields. The reaction provides a safe, efficient and economic approach for the synthesis of various 1,2,3 triazoles. The reaction has many advantages like shorter reaction times, good yields of products and isolation of the products without the need of column chromatography. By using knoevenagel reaction under physical grinding with alkylating agents prepared various 1,2,3 triazoles.