The receptor for advanced glycation endproducts (RAGE) is an ubiquitous, transmembrane, immunoglobulin-like receptor that exists in multiple isoforms and binds to a diverse range of endogenous ...extracellular ligands and intracellular effectors. Ligand binding at the extracellular domain of RAGE initiates a complex intracellular signaling cascade, resulting in the production of reactive oxygen species (ROS), immunoinflammatory effects, cellular proliferation, or apoptosis with concomitant upregulation of RAGE itself. To date, research has mainly focused on the correlation between RAGE activity and pathological conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegeneration. Because RAGE plays a role in many pathological disorders, it has become an attractive target for the development of inhibitors at the extracellular and intracellular domains. This review describes the role of endogenous RAGE ligands/effectors in normo- and pathophysiological processes, summarizes the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.
When reacted in the presence of external oxidants, gold complexes are capable of catalyzing oxidative homo- and cross-coupling reactions involving the formation of new C-C bonds. Over the last few ...years, several cascade processes have been reported in which coupling is preceded by a gold-mediated aryl C-H functionalization or nucleophilic addition. These reactions combine the unique reactivity of gold with oxidative coupling, enabling the construction of C-C bonds between coupling partners that are not easily accessed using alternative catalysts. In this Concept paper, the development of gold-catalyzed oxidative coupling reactions is discussed focusing on C-C bond-forming reactions of broad synthetic appeal.
Positron emission tomography (PET) is a powerful functional imaging technique that requires the use of positron emitting nuclides. Carbon-11 (
11
C) radionuclide has several advantages related to the ...ubiquity of carbon atoms in biomolecules and the conservation of pharmacological properties of the molecule upon isotopic exchange of carbon-12 with carbon-11. However, due to the short half-life of
11
C (20.4 minutes) and the low scale with which it is produced by the cyclotron (sub-nanomolar concentrations), quick, robust and chemospecific radiolabelling strategies are required to minimise activity loss during incorporation of the
11
C nuclide into the final product. To address some of the constraints of working with
11
C, the use of silicon-based chemistry for
11
C-labelling was proposed as a rapid and effective route for radiopharmaceutical production due to the broad applicability and high efficiency showed in organic chemistry. In the past years several organic chemistry methodologies have been successfully applied to
11
C-chemistry. In this short review, we examine silicon-based
11
C-chemistry, with a particular emphasis on the radiotracers that have been successfully produced and potential improvements to further expand the applicability of silicon in radiochemistry.
The use of silicon-based reagents and precursors for carbon-11 labelling has shown wide applicability and robustness with short reaction times using mild conditions. In this review, recent advances and future perspectives are examined.
Hydrogen
Ccyanide (
CHCN) is a versatile
C-labelling agent for the production of
C-labelled compounds used for positron emission tomography (PET). However, the traditional method for
CHCN ...production requires a dedicated infrastructure, limiting accessibility to
CHCN. Herein, we report a simple and efficient
CHCN production method that can be easily implemented in
C production facilities. The immediate production of
CHCN was achieved by passing gaseous
Cmethyl iodide (
CCH
I) through a small two-layered reaction column. The first layer contained an
-oxide and a sulfoxide for conversion of
CCH
I to
Cformaldehyde (
CCH
O). The
CCH
O produced was subsequently converted to
CHCN in a second layer containing hydroxylamine-
-sulfonic acid. The yield of
CHCN produced by the current method was comparable to that of
CHCN produced by the traditional method. The use of oxymatrine and diphenyl sulfoxide for
CCH
O production prevented deterioration of the molar activity of
CHCN. Using this method, compounds labelled with
CHCN are now made easily accessible for PET synthesis applications using readily available labware, without the need for the 'traditional' dedicated cyanide synthesis infrastructure.
11CCarbon dioxide (11CCO2) and 11Ccarbon monoxide (11CCO) are 2 attractive precursors for labelling the carbonyl position (C═O) in a vast range of functionalised molecules (eg, ureas, amides, and ...carboxylic acids). The development of radiosynthetic methods to produce functionalised 11C‐labelled compounds is required to enhance the radiotracers available for positron emission tomography, molecular, and medical imaging applications. Following a brief summary of secondary 11C‐precursor production and uses, the review focuses on recent progress with direct 11C‐carboxylation routes with 11CCO2 and 11C‐carbonylation with 11CCO. Novel approaches to generate 11CCO using CO‐releasing molecules (CO‐RMs), such as silacarboxylic acids and disilanes, applied to radiochemistry are described and compared with standard 11CCO production methods. These innovative 11CCO synthesis strategies represent efficient and reliable 11CCO production processes, enabling the widespread use of 11CCO chemistry within the wider radiochemistry community.
A novel carboxylation radiosynthesis methodology is described starting from cyclotron-produced 11CCO2 and fluoride-activated silane derivatives. Six carbon-11 labelled carboxylic acids were obtained ...from their corresponding trimethylsilyl and trialkoxysilyl precursors in a one-pot labelling methodology. The radiochemical yields ranged from 19% to 93% within 12 minutes post 11CCO2 delivery with a trapping efficiency of 21–89%.
The development of a fast and novel methodology to generate carbon‐11 carbon monoxide (11CCO) from cyclotron‐produced carbon‐11 carbon dioxide (11CCO2) mediated by a fluoride‐activated disilane ...species is described. This methodology allows up to 74 % conversion of 11CCO2 to 11CCO using commercially available reagents, readily available laboratory equipment and mild reaction conditions (room temperature). As proof of utility, radiochemically pure carbonyl‐11CN‐benzylbenzamide was successfully synthesized from produced 11CCO in up to 74 % radiochemical yield (RCY) and >99 % radiochemical purity (RCP) in ≤10 min from end of 11CCO2 delivery.
Radio Ga Ga: Release of 11CCO up to 74 % at room temperature within 10 min from the end of 11CCO2 production.
An (Au)some coupling! Gold‐catalyzed cascade CO cyclizations of benzyl‐substituted allenoate esters followed by intramolecular oxidative CC cross‐coupling involving aryl CH functionalization were ...performed with Selectfluor as the oxidant (see scheme). This operationally simple and mild procedure benefits from complete axis‐to‐center chirality transfer and allows for the preparation of surprisingly uncommon tricyclic motifs.
Over recent years, within the community of radiopharmaceutical sciences, there has been an increased incidence of incorrect usage of established scientific terms and conventions, and even the ...emergence of ‘self-invented’ terms. In order to address these concerns, an international Working Group on ‘Nomenclature in Radiopharmaceutical Chemistry and related areas’ was established in 2015 to achieve clarification of terms and to generate consensus on the utilisation of a standardised nomenclature pertinent to the field.
Upon open consultation, the following consensus guidelines were agreed, which aim to:•Provide a reference source for nomenclature good practice in the radiopharmaceutical sciences.•Clarify the use of terms and rules concerning exclusively radiopharmaceutical terminology, i.e. nuclear- and radiochemical terms, symbols and expressions.•Address gaps and inconsistencies in existing radiochemistry nomenclature rules.•Provide source literature for further harmonisation beyond our immediate peer group (publishers, editors, IUPAC, pharmacopoeias, etc.).
A copper‐catalysed radiosynthesis of carbon‐11 radiolabelled carboxylic acids was developed by reacting terminal alkynes and cyclotron‐produced carbon‐11 carbon dioxide (11CCO2) in the presence of ...1,8‐diazabicyclo5.4.0undec‐7‐ene (DBU). A small library of 11C‐labelled propiolic acid derivatives were obtained with a total synthesis time of 15 min from end of bombardment (EOB) with a (non‐isolated) radiochemical yield ranging from 7% to 28%.
A copper‐catalysed radiosynthesis of carbon‐11 radiolabelled carboxylic acids was developed by reacting terminal alkynes and cyclotron‐produced carbon‐11 carbon dioxide. A small library of 11C‐labelled propiolic acid derivatives was obtained with a total synthesis time of 15 min from end of bombardment (EOB) with a (nonisolated) radiochemical yield ranging from 7% to 28%.
PDF
![Recent progress in [11C]car...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0362-4803_1099-1344/small "Recent progress in [11C]carbon dioxide ([11C]CO2) and [11C]carbon monoxide ([11C]CO) chemistry")
