Scoparone chemical modification into semi-synthetic analogues featuring 3-substitution for their anti-inflammatory activity.

Natural products (NPs) continue to serve as a structural model for the development of new bioactive molecules and improve the process of identifying novel medicines. The biological effects of coumarins, one of the most researched compounds among NPs, are currently being thoroughly investigated. In the present investigation, we reported the synthesis of nineteen semi-synthetic 3-substituted scoparone analogues, followed by their characterization using analytical methods such as NMR, HPLC, and HRMS. All compounds screened for in vitro and in vivo study for their ability to reduce inflammation. The SAR study worked effectively for this particular scoparone 3-substitution, as compounds 3, 4, 9, 16, 18, and 20 displayed improved in vitro results for TNF-α than the parent molecule. Similarly, compounds 3, and 17 showed a higher percentage of IL-6 inhibition. Compounds 3, 4, and 12 have also been identified by in vivo studies as promising candidates with higher percent inhibition than the parent scoparone molecule. As evident from all in vitro and in vivo studies, compound 3 showed the most potent anti-inflammatory activity among all.

Plasmonic visible-near infrared photothermal activation of olefin metathesis enabling photoresponsive materials.

Light-induced catalysis and thermoplasmonics are promising fields creating many opportunities for innovative research. Recent advances in light-induced olefin metathesis have led to new applications in polymer and material science, but further improvements to reaction scope and efficiency are desired. Herein, we present the activation of latent ruthenium-based olefin metathesis catalysts via the photothermal response of plasmonic gold nanobipyramids. Simple synthetic control over gold nanobipyramid size results in tunable localized surface plasmon resonance bands enabling catalyst initiation with low-energy visible and infrared light. This approach was applied to the ROMP of dicyclopentadiene, affording plasmonic polymer composites with exceptional photoresponsive and mechanical properties. Moreover, this method of catalyst activation was proven to be remarkably more efficient than activation through conventional heating in all the metathesis processes tested. This study paves the way for providing a wide range of photoinduced olefin metathesis processes in particular and photoinduced latent organic reactions in general by direct photothermal activation of thermally latent catalysts.

Photoelectrochemical alcohols oxidation over polymeric carbon nitride photoanodes with simultaneous H2 production.

The photoelectrochemical oxidation of organic molecules into valuable chemicals is a promising technology, but its development is hampered by the poor stability of photoanodic materials in aqueous solutions, low faradaic efficiency, low product selectivity, and a narrow working pH range. Here, we demonstrate the synthesis of value-added aldehydes and carboxylic acids with clean hydrogen (H2) production in water using a photoelectrochemical cell based solely on polymeric carbon nitride (CN) as the photoanode. Isotope labeling measurements and DFT calculations reveal a preferential adsorption of benzyl alcohol and molecular oxygen to the CN layer, enabling fast proton abstraction and oxygen reduction, which leads to the synthesis of an aldehyde at the first step. Further oxidation affords the corresponding acid. The CN photoanode exhibits excellent stability (>40 h) and activity for the oxidation of a wide range of substituted benzyl alcohols with high yield, selectivity (up to 99%), and faradaic efficiency (>90%).

Metal-Free Photochemical Olefin Isomerization of Unsaturated Ketones via 1,5-Hydrogen Atom Transfer.

The photochemical isomerization of α,ß- to ß,γ-unsaturated ketones through a 1,5-hydrogen atom transfer mechanism under mild conditions with high efficiency and selectivity is reported. The reaction is carried out in the absence of metal catalysts or other additives, and its stereoselectivity can be tuned by selecting appropriate solvent mixtures. The reaction's scope and tolerance towards functional groups, including light-sensitive halogens, free acids and alcohols, were studied, providing reliable access to a wide variety of ß,γ-unsaturated ketones. This methodology details the deconjugation of a wide range of unsaturated ketones and, when combined with olefin metathesis, provides an efficient process for either dehomologation or one-carbon double-bond migration of terminal alkenes.

Light-Activated Olefin Metathesis: Catalyst Development, Synthesis, and Applications.

The most important means for tuning and improving a catalyst's properties is the delicate exchange of the ligand shell around the central metal atom. Perhaps for no other organometallic-catalyzed reaction is this statement more valid than for ruthenium-based olefin metathesis. Indeed, even the simple exchange of an oxygen atom for a sulfur atom in a chelated ruthenium benzylidene about a decade ago resulted in the development of extremely stable, photoactive catalysts. This Account presents our perspective on the development of dormant olefin metathesis catalysts that can be activated by external stimuli and, more specifically, the use of light as an attractive inducing agent.The insight gained from a deeper understanding of the properties of cis-dichlororuthenium benzylidenes opened the doorway for the systematic development of new and efficient light-activated olefin metathesis catalysts and catalytic chromatic-orthogonal synthetic schemes. Following this, ways to disrupt the ligand-to-metal bond to accelerate the isomerization process that produced the active precatalyst were actively pursued. Thus, we summarize herein the original thermal activation experiments and how they brought about the discoveries of photoactivation in the sulfur-chelated benzylidene family of catalysts. The specific wavelengths of light that were used to dissociate the sulfur-ruthenium bond allowed us to develop noncommutative catalytic chromatic-orthogonal processes and to combine other photochemical reactions with photoinduced olefin metathesis, including using external light-absorbing molecules as "sunscreens" to achieve novel selectivities. Alteration of the ligand sphere, including modifications of the N-heterocyclic carbene (NHC) ligand and the introduction of cyclic alkyl amino carbene (CAAC) ligands, produced more efficient light-induced activity and special chemical selectivity. The use of electron-rich sulfoxides and, more prominently, phosphites as the agents that induce latency widened the spectrum of light-induced olefin metathesis reactions even further by expanding the colors of light that may now be used to activate the catalysts, which can be used in applications such as stereolithography and 3D printing of tough metathesis-derived polymers.

Thiourea-Mediated Halogenation of Alcohols.

The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.

Fluoride-Mediated Dephosphonylation of α-Diazo-ß-carbonyl Phosphonates.

The possibility of fluoride-mediated selective dephosphonylation of α-diazo-ß-carbonyl phosphonates such as the Ohira-Bestmann reagent has been proposed and executed. The resulting α-diazocarbonyl intermediates undergo a (3 + 2)-cycloaddition at room temperature with conjugated olefins and benzynes. Interestingly, under the current conditions, the resulting cycloaddition products underwent either N-acylation (with excess α-diazo-ß-carbonyl phosphonates) or Michael addition (with conjugated olefins).

Ir(III)-Catalyzed Carbenoid Functionalization of Benzamides: Synthesis of N-Methoxyisoquinolinediones and N-Methoxyisoquinolinones.

A mild and efficient Ir(III)-catalyzed C-H carbenoid functionalization strategy has been developed to access N-methoxyisoquinolinediones and N-methoxyisoquinolinones. The reaction proceeds efficiently in high yield at room temperature over a broad range of substrates without requirement of any additional oxidants or a base.

Ir(III)-Catalyzed Synthesis of Isoquinoline N-Oxides from Aryloxime and α-Diazocarbonyl Compounds.

An efficient Ir(III)-catalyzed C-H activation and annulations of aryloxime with α-diazocarbonyl compounds has been developed for the synthesis of substituted isoquinoline N-oxides. The reaction proceeds under mild atmospheric conditions, without any external oxidants and releases N2 and H2O as the byproducts. In addition, synthetic applications of the N-oxide products have been established by performing further functionalization. An interesting dimeric iridacyclic complex allied through a bis-silver carboxylate bridge has been isolated that efficiently catalyzed the reaction.