σ-Bond insertion reactions of two strained diradicaloids.

The development of new synthetic methodologies are instrumental for enabling the discovery of new medicines. Those methods that provide efficient access to structural alternatives for aromatic compounds (i.e.

The power of three: Retatrutide's role in modern obesity and diabetes therapy.

The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It required the development of novel therapeutic approaches. Retatrutide is a groundbreaking triple agonist that targets glucagon receptors, gastric inhibitory polypeptide, and glucagon-like peptide-1.

A solution to the anti-Bredt olefin synthesis problem.

The π-bonds in unsaturated organic molecules are typically associated with having well-defined geometries that are conserved across diverse structural contexts. Nonetheless, these geometries can be distorted, leading to heightened reactivity of the π-bond. Although π-bond-containing compounds with bent geometries are well utilized in synthetic chemistry, the corresponding leveraging of π-bond-containing compounds that display twisting or pyramidalization remains underdeveloped.

Fragment-Guided Genome Mining of Octacyclic Cyclophane Alkaloids from Fungi.

Nature uses compact but functionalized biosynthetic fragments as building blocks to generate complex natural products. To leverage this strategy for the discovery of natural products with new scaffolds, we performed genome mining to identify biosynthetic gene clusters (BGCs) in fungi that embed genes that can synthesize targeted fragments. The three-enzyme pathway that biosynthesizes the strained dityrosine cyclophane in the herquline A pathway was used to identify a large number of potential BGCs that may use the cyclophane as a fragment.

Diels-Alder Cycloadditions of Oxacyclic Allenes and α-Pyrones.

Reactions of α-pyrones with oxacyclic allenes in Diels-Alder trappings are described. We investigate regioselectivity trends and perform competition experiments to assess the influence of structural and electronic features on relative reaction rates. We also demonstrate the stereospecific trapping of an oxacyclic allene, which proceeds in high optical yield.

Access to Complex Scaffolds Through [2 + 2] Cycloadditions of Strained Cyclic Allenes.

We report the strain-induced [2 + 2] cycloadditions of cyclic allenes for the assembly of highly substituted cyclobutanes. By judicious choice of trapping agent, complex scaffolds bearing heteroatoms, fused rings, contiguous stereocenters, spirocycles, and quaternary centers are ultimately accessible. Moreover, we show that the resulting cycloadducts can undergo thermal isomerization.

Total Synthesis of Lissodendoric Acid A.

We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A . These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis.

Evaluation of Retro-Aldol vs Retro-Carbonyl-Ene Mechanistic Pathways in a Complexity-Generating C-C Bond Fragmentation.

We report an experimental and computational investigation of the likely mechanism of a cascade reaction. The reaction involves an intramolecular Diels-Alder reaction, followed by a C-C bond cleavage, to afford a complex bridged bicyclic product. As multiple reaction pathways could be envisioned for the latter step, the mechanism of the C-C bond cleavage step was investigated.

Generation and reactivity of unsymmetrical strained heterocyclic allenes.

Strained cyclic allenes are short-lived intermediates that confine a functional group with a preferred linear geometry, an allene, into a small ring, inducing strain-driven reactivity. Nitrogen-containing variants, or azacyclic allenes, have proved valuable for the assembly of complex nitrogen-containing compounds. Whereas 3,4-azacyclic allenes, which bear a symmetrical core, have been the focus of multiple studies, their unsymmetrical 2,3-azacyclic counterparts have remained underexplored.

Enantioselective nickel-catalyzed Mizoroki-Heck cyclizations of amide electrophiles.

Amide cross-couplings that rely on C-N bond activation by transition metal catalysts have emerged as valuable synthetic tools. Despite numerous discoveries in this field, no catalytic asymmetric variants have been disclosed to date. Herein, we demonstrate the first such transformation, which is the Mizoroki-Heck cyclization of amide substrates using asymmetric nickel catalysis.

The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review.

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression.

Small molecule inhibition of RNA binding proteins in haematologic cancer.

In recent years, advances in biomedicine have revealed an important role for post-transcriptional mechanisms of gene expression regulation in pathologic conditions. In cancer in general and leukaemia specifically, RNA binding proteins have emerged as important regulator of RNA homoeostasis that are often dysregulated in the disease state. Having established the importance of these pathogenetic mechanisms, there have been a number of efforts to target RNA binding proteins using oligonucleotide-based strategies, as well as with small organic molecules.

The role of membrane trafficking and retromer complex in Parkinson's and Alzheimer's disease.

Membrane trafficking is a physiological process encompassing different pathways involved in transporting cellular products across cell membranes to specific cell locations via encapsulated vesicles. This process is required for cells to mature and function properly, allowing them to adapt to their surroundings. The retromer complex is a complex composed of nexin proteins and peptides that play a vital role in the endosomal pathway of membrane trafficking.

Beyond symptoms: Unlocking the potential of coronary calcium scoring in the prevention and treatment of coronary artery disease.

Coronary Artery Disease (CAD) represents a persistent global health menace, particularly prevalent in Eastern European nations. Often asymptomatic until its advanced stages, CAD can precipitate life-threatening events like myocardial infarction or stroke. While conventional risk factors provide some insight into CAD risk, their predictive accuracy is suboptimal.

A symmetry-driven approach toward the total synthesis of dodecahedrane.

Herein, we describe our progress toward the total synthesis of dodecahedrane, a complex and highly symmetrical hydrocarbon that bears twelve fused rings arranged in a cage-like architecture. Central to our approach is a late-stage [2+2+2+2+2] polyene cyclization cascade, which is expected to construct five new bonds and ten new rings in a single transformation. Toward this end, we describe efforts to synthesize key monomeric fragments, along with successful dimerization studies using a pinacol coupling approach.

Facile synthesis of 2-aza-9,10-diphenylanthracene and the effect of precise nitrogen atom incorporation on OLED emitters performance.

Polycyclic aromatic hydrocarbons (PAHs) are important compounds in materials chemistry, particularly for optoelectronic applications. One strategy for tuning PAH properties involves the net exchange of carbon atoms for heteroatoms, such as nitrogen. We report a comparative study of the well-known fluorophore 9,10-diphenylanthracene with an aza analog.

Studies Pertaining to the Emerging Cannabinoid Hexahydrocannabinol (HHC).

We report studies pertaining to two isomeric hexahydrocannabinols (HHCs), ()-HHC and ()-HHC, which are derivatives of the psychoactive cannabinoids Δ- and Δ-THC. HHCs have been known since the 1940s, but have become increasingly available to the public in the United States and are typically sold as a mixture of isomers. We show that ()-HHC and ()-HHC can be prepared using hydrogen-atom transfer reduction, with ()-HHC being accessed as the major diastereomer.

Inequitable access to Ebola vaccines and the resurgence of Ebola in Africa: A state of arts review.

The Ebola virus, a member of the filoviridae family of viruses, is responsible for causing Ebola Virus Disease (EVD) with a case fatality rate as high as 50%. The largest EVD outbreak was recorded in West Africa from March 2013 to June 2016, leading to over 28 000 cases and 11 000 deaths. It affected several countries, including Nigeria, Senegal, Guinea, Liberia, and Sierra Leone.

Electrochemical Oxidation of Δ-Tetrahydrocannabinol at Nanomolar Concentrations.

With increasing marijuana legalization, there is a growing need for technology that can determine if an individual is impaired due to recent marijuana usage. The electrochemical oxidation of Δ-THC to form its corresponding quinones can be used as a framework to develop an electrochemical sensor for Δ-THC. This study describes an electrochemical oxidation of Δ-THC that uses a copper anode, a platinum cathode, and an atmosphere of oxygen.

Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B.

We report an approach to the core of the manzamine alkaloid keramaphidin B that relies on the strain-promoted cycloaddition of an azacyclic allene with a pyrone trapping partner. The cycloaddition is tolerant of nitrile and primary amide functional groups and can be complemented with a subsequent retro-Diels-Alder step. These efforts demonstrate that strained cyclic allenes can be used to build significant structural complexity and should encourage further studies of these fleeting intermediates.

Total Synthesis of Phenanthroindolizidines Using Strained Azacyclic Alkynes.

We report a concise approach to phenanthroindolizidine alkaloids, wherein strained azacyclic alkynes are intercepted in Pd-catalyzed annulations. Two types of strained intermediates were evaluated: a functionalized piperidyne and a new strained intermediate, an indolizidyne. We show that each can be employed, ultimately allowing access to three natural products: tylophorine, tylocrebine, and isotylocrebine.