Synthesis of benzo[b]furans by intramolecular C–O bond formation using iron and copper catalysis

One-pot processes for the synthesis of benzo[b]furans from 1-aryl- or 1-alkylketones using nonprecious transition metal catalysts have been developed. Regioselective iron(III)-catalyzed halogenation of the aryl ring, followed by iron- or copper-catalyzed O-arylation allowed the synthesis of various structural analogues, including the benzo[b]furan-derived natural products corsifuran C, moracin F, and caleprunin B

Iron-catalyzed regioselective synthesis of 2-arylbenzoxazoles and 2-arylbenzothiazoles via alternative reaction pathways

A one‐pot regioselective method for the preparation of 2‐arylbenzoxazoles from N‐arylbenzamides has been developed using iron(III)‐catalyzed bromination of the aryl ring, followed by copper(I)‐catalyzed O‐cyclization with the benzamide side chain. In contrast, reaction of N‐arylthiobenzamides with N‐bromosuccinimide and iron triflimide led directly to the isolation of the corresponding 2‐arylbenzothiazoles via intramolecular C–S bond formation. Mechanistic and control experiments suggest that in this case, bromination occurs at the sulfur atom, resulting in a reactive intermediate that can undergo electrophilic aromatic substitution and S‐cyclization. The scope of both processes was explored yielding a range of structural analogues, including a pharmaceutically active compound for the treatment of Duchenne muscular dystrophy and an affinity agent of the amyloid‐beta protein in Alzheimer's disease

Recent advances in transition-metal-catalyzed, directed Aryl C-H/N-H cross coupling reactions

Amination and amidation of aryl compounds using a transition-metal-catalyzed cross-coupling reaction typically involves prefunctionalization or preoxidation of either partner. In recent years, a new class of transition-metal-catalyzed cross-dehydrogenative coupling reaction has been developed for the direct formation of aryl C–N bonds. This short review highlights the substantial progress made for ortho-C–N bond formation via transition-metal-catalyzed chelation-directed aryl C–H activation and gives an overview of the challenges that remain for directed meta- and para-selective reactions

Five axioms for location functions on median graphs

__Abstract__ In previous work, two axiomatic characterizations were given for the median function on median graphs: one involving the three simple and natural axioms anonymity, betweenness and consistency; the other involving faithfulness, consistency and ½-Condorcet. To date, the independence of these axioms has not been a serious point of study. The aim of this paper is to provide the missing answers. The independent subsets of these five axioms are determined precisely and examples provided in each case on arbitrary median graphs. There are three cases that stand out. Here non-trivial examples and proofs are needed to give a full answer. Extensive use of the structure of median graphs is used throughout

Iron(III)-catalyzed chlorination of activated arenes

A general and regioselective method for the chlorination of activated arenes has been developed. The transformation uses iron(III) triflimide as a powerful Lewis acid for the activation of N-chlorosuccinimide and the subsequent chlorination of a wide range of anisole, aniline, acetanilide and phenol derivatives. The reaction was utilized for the late-stage mono- and di-chlorination of a range of target compounds such as the natural product nitrofungin, the antibacterial agent chloroxylenol and the herbicide chloroxynil. The facile nature of this transformation was demonstrated with the development of one-pot tandem iron-catalyzed dihalogenation processes allowing highly regioselective formation of different carbon-halogen bonds. The synthetic utility of the resulting dihalogenated aryl compounds as building blocks was established with the synthesis of natural products and pharmaceutically relevant targets

Current and emerging approaches to noncompetitive AR inhibition

The Androgen Receptor (AR) has been shown to be a key determinant in the pathogenesis of castration-resistant prostate cancer (CRPC). Current standard of care therapies target the ligand-binding domain of the receptor, and afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current anti-androgens show promise for overcoming treatment resistance. In this review we present an authoritative summary of molecules that non-competitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential future therapies. The overall quality of lead candidates in the area of non-competitive AR inhibition is discussed, and identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned for first in human applications

Functionalized tetrazoles as latent active esters in the synthesis of amide bonds

We report the use of N-2,4-dinitrophenyltetrazoles as latent active esters (LAEs) in the synthesis of amide bonds. Activating the tetrazole generates an HOBt-type active ester without the requirement for exogenous coupling agents. The methodology was widely applicable to a range of substrates, with up to quantitative yields obtained. The versatility and functional group tolerance were exemplified with the one-step synthesis of various pharmaceutical agents, and the N-acylation of resin bound peptides

[18F]LW223 has low non-displaceable binding in murine brain, enabling high sensitivity TSPO PET imaging

Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [18F]LW223, in mice and specifically assess its volume of non-displaceable binding (VND) in brain as well as investigate the use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F]LW223 and varying concentrations of LW223 (0.003–0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values (SUV) and apparent volume of distribution (VTapp), were investigated. [18F]LW223 had low VND in the brain (<10% of total binding) and low radiometabolism (∼15–20%). The 2-tissue compartment model provided the best fit for [18F]LW223 PET data, although its correlation with SUV90–120min or VTapp allowed for [18F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F]LW223 has the required properties to become a successful TSPO PET radiotracer