Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

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Aryl-aryl bond formation one century after the discovery of the Ullmann reaction.

The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

This Review covers recent progress on near-infrared fluorescence imaging for preclinical animal studies and clinical diagnostics and interventions.

Near-infrared fluorophores for biomedical imaging

Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

Organic Azides: An Exploding Diversity of a Unique Class of Compounds

Alzheimer's Disease (AD) remains one of the most challenging health-related issues for our society. It is becoming increasingly prevalent, especially in developed countries, due to the rising life expectancy and, moreover, represents a considerable economic burden worldwide. All efforts at the discovery of new diagnostic and therapeutic tools in the last decades have invariably met with failure, making AD an incurable illness and underscoring the need for new approaches. In recent years, theranostic agents have emerged as an interesting strategy. They are molecules able to simultaneously provide diagnostic information and deliver therapeutic activity, allowing for the assessment of the molecule activity, the organism response and the pharmacokinetics. This makes these compounds promising for streamlining research on AD drugs and for their application in personalized medicine. We review here the field of small-molecule theranostic agents as promising tools for the development of novel diagnostic and therapeutic resources against AD, highlighting the positive and significant impact that theranostics can be expected to have in the near future in clinical practice. 

Small-molecule theranostics in Alzheimer's disease.

Chemistry of Pyrazino[2,1-b]quinazoline-3,6-diones

Concise Preparation of 1,8‐Diazaanthracene‐2,7,9,10‐tetraones. Two Alternative Syntheses of the Natural Antifolate Diazaquinomycin A.

Publisher Summary Protein degradation is essential for the cell to supply fresh amino acids for protein synthesis and also to remove unneeded proteins including excess enzymes and transcription factors that are no longer required or damaged. Proteasome inhibitors containing aldehyde or ketone functions react reversibly with the threonine hydroxyl to produce the corresponding acetals. In response to angiogenic stimuli, endothelial proteases initiate the breakdown of the surrounding extracellular matrix, which allows the migration of proliferating endothelial cells and their growth to form lumens. Besides their role in cancer treatment, they are also being studied as targets for arthritis and emphysema because of their role in collagen degradation. The design of the first generation of MMP inhibitors relied on the preparation of peptide and peptide-like compounds that combine backbone features that interact with enzyme subsites and functional groups capable of coordination with zinc. Endostatin is a polypeptide of 184 amino acids, corresponding to the globular domain found at the C-terminal of type XVIII collagen, and it is the most studied of the endogenous angiogenesis inhibitors.

Other Approaches to Targeted Therapy

Microwave irradiation leads to a considerable improvement of the cyclocondensation between anthranilic acid and lactim ethers derived from piperazine-2,5-diones in terms of reaction times, yields, and stereocenter integrity. This reaction has been used to prepare some derivatives of the pyrazino[2,1- B]quinazoline-3,6-dione system present in many quinazoline alkaloids. It could also be applied to the synthesis of compounds containing the complete hexacyclic ring system of the anti-MDR natural product N-acetyl-ardeemin, and other comprising the pentacyclic framework of circumdatin E. The microwave-assisted reaction was also much better than the thermal one when applied to a bis-lactim ether, leading to the corresponding pentacyclic pyrazino[2,1- B:5,4- B′]diquinazoline-8,16-dione in excellent yield.

J. Carlos Menéndez

Papers

Small-molecule theranostics in Alzheimer's disease.

Chemistry of Pyrazino[2,1-b]quinazoline-3,6-diones

Concise Preparation of 1,8‐Diazaanthracene‐2,7,9,10‐tetraones. Two Alternative Syntheses of the Natural Antifolate Diazaquinomycin A.

Other Approaches to Targeted Therapy

Microwave‐Assisted, Solvent‐Free Synthesis of Several Quinazoline Alkaloid Frameworks.