Design and Mechanistic Insights into α-Helical -Terphenyl Guanidines as Potent Small-Molecule Antifreeze Agents.

Ice formation is a critical challenge across multiple fields, from industrial applications to biological preservation. Inspired by natural antifreeze proteins, we designed and synthesized a new class of small-molecule antifreezes based on α-helical -terphenyl scaffolds with guanidine side chains. These -terphenyl guanidines , among the smallest molecules that mimic α-helical structures, exhibit potent ice recrystallization inhibition (IRI) activity, similar to that of existing large α-helical antifreeze compounds.

Pentafluoroethylation of Carbonyl Compounds by HFC-125 the Encapsulation of the K Cation with Glymes.

A simple protocol to overcome the explosive pentafluoroethylation of carbonyl compounds by HFC-125 is described. The use of potassium (K) bases with triglyme or tetraglyme as a solvent safely yields the pentafluoroethylation products in good to high yields. The experimental results suggest that an encapsulation of the K cation by glymes as K(glyme) inhibits the contact between the K cation and the reactive anionic pentafluoroethyl counterion, preventing their transformation into KF and explosive tetrafluoroethylene (TFE).

Chemical Aspects of Human and Environmental Overload with Fluorine.

Over the last 100-120 years, due to the ever-increasing importance of fluorine-containing compounds in modern technology and daily life, the explosive development of the fluorochemical industry led to an enormous increase of emission of fluoride ions into the biosphere. This made it more and more important to understand the biological activities, metabolism, degradation, and possible environmental hazards of such substances. This comprehensive and critical review focuses on the effects of fluoride ions and organofluorine compounds (mainly pharmaceuticals and agrochemicals) on human health and the environment.

Pauson-Khand reaction of fluorinated compounds.

The Pauson-Khand reaction (PKR) is one of the key methods for the construction of cyclopentenone derivatives, which can in turn undergo diverse chemical transformations to yield more complex biologically active molecules. Despite the increasing availability of fluorinated building blocks and methodologies to incorporate fluorine in compounds with biological interest, there have been few significant advances focused on the fluoro-Pauson-Khand reaction, both in the inter- and intramolecular versions. Furthermore, the use of vinyl fluorides as olefinic counterparts had been completely overlooked.

Diastereoselective Synthesis of Enantioenriched Trifluoromethylated Ethylenediamines and Isoindolines Containing Two Stereogenic Carbon Centers by Nucleophilic Trifluoromethylation Using HFC-23.

Fluoroform, HFC-23, is an industrial byproduct from the synthesis of polytetrafluoroethylene and is a vastly underused resource; however, its physicochemical properties have hindered progress toward synthetic uses. Herein, we describe the use of HFC-23 as a cheap trifluoromethylating agent in two reactions for the highly diastereoselective synthesis of medicinally attractive chiral amines with two stereogenic carbon centers: a base-dependent, stereodivergent nucleophilic addition to synthesize enantioenriched vicinal diamines and a tandem nucleophilic addition/aza-Michael sequence toward enantioenriched isoindolines.

Nucleic acid recognition and antiviral activity of 1,4-substituted terphenyl compounds mimicking all faces of the HIV-1 Rev protein positively-charged α-helix.

Small synthetic molecules mimicking the three-dimensional structure of α-helices may find applications as inhibitors of therapeutically relevant protein-protein and protein-nucleic acid interactions. However, the design and use of multi-facial helix mimetics remains in its infancy. Here we describe the synthesis and application of novel bilaterally substituted p-terphenyl compounds containing positively-charged aminoalkyl groups in relative 1,4 positions across the aromatic scaffold.

The Fluoro-Pauson-Khand Reaction in the Synthesis of Enantioenriched Nitrogenated Bicycles Bearing a Quaternary C-F Stereogenic Center.

A variety of enantioenriched fluorinated 6-cyclopenta[]pyridin-6-one bicycles, a scaffold present in several classes of monoterpenic alkaloids with varied biological activity, were synthesized in just five steps from simple aldehyde starting materials. The synthesis presented wide functional group tolerance and moderate to high yields and diastereoselectivities and could be carried out on a gram scale. These products were suitable for further transformations, such as hydrogenation and deprotection of the -butylsulfonyl protecting group.

Fluorine-Containing Drugs Approved by the FDA in 2018.

Over the last two decades, fluorine substitution has become one of the essential structural traits in modern pharmaceuticals. Thus, about half of the most successful drugs (blockbuster drugs) contain fluorine atoms. In this review, we profile 17 fluorine-containing drugs approved by the food and drug administration (FDA) in 2018.

Copper-Catalyzed Regioselective Synthesis of ()-β-Fluorovinyl Sulfones.

Organofluorine compounds are finding increasing application in a variety of fields such as pharmaceutical, agrochemical, and material sciences. However, given the scarcity of fluorine-containing natural products, advancement in this area depends almost entirely on the development of new synthetic methodologies. In this article, we present the synthesis of a series of previously undescribed ()-β-fluorovinyl sulfones via a simple copper-catalyzed addition of hydrogen fluoride to alkynyl sulfone starting materials in varying yields and selectivities.

Recent advances in the synthesis of functionalised monofluorinated compounds.

Over the past few years, we have tackled the synthesis of interesting monofluorinated organic molecules, such as: dihydronaphthalene derivatives, β-fluoro sulfones and related carbonyl compounds, fluorohydrins and allylic alcohols. Overall, a wide range of modern synthetic techniques are covered in this feature article including transition-metal, photo- and organocatalysis, nucleophilic and electrophilic fluorinations, chiral auxiliaries and enantioselective catalysis.

Metal-Free and User-Friendly Regioselective Hydroxyfluorination of Olefins.

A simple, user-friendly, metal-free protocol for the regioselective anti-Markovnikov hydrofluorination of olefins using readily available and inexpensive reagents has been developed. This new approach displays a broader scope than previously reported methodologies and has been applied to the late-stage fluorination of a complex molecule, giving rise to a fluorosteroid derivative. The stereochemistry of the process has also been studied in some detail.

Asymmetric Allylation/RCM-Mediated Synthesis of Fluorinated Benzo-Fused Bicyclic Homoallylic Amines As Dihydronaphthalene Derivatives.

Enantiomerically enriched fluorinated benzo-fused bicyclic homoallylic amines have been synthesized through an asymmetric allylation/ring closing metathesis (RCM) sequence. This sequence has been carried out using α-trifluoromethylstyrene derivatives as key intermediates, synthesized by microwave radiation. The great deactivating effect exerted by such substituents has been brought to light by a comparative study.

Asymmetric Synthesis of Monofluorinated 1-Amino-1,2-dihydronaphthalene and 1,3-Amino Alcohol Derivatives.

Enantioenriched 1-amino-4-fluoro-1,2-dihydronaphthalene derivatives are accessed via two complementary synthetic strategies. The careful optimization of the reaction conditions required for the elimination step in one route has allowed both the identification of an anchimerically assisted reaction pathway and, more importantly, access to a divergent reaction pathway toward fluorinated 1,3-amino alcohols from a common intermediate just by adjusting the number of equivalents of base used.