Publications by authors named "Adam Noble"

At present, little is known about the outcomes measured in studies assessing the effectiveness of treatments for adults with epilepsy. As part of a wider project developing a Core Outcome Set for clinical trials for adults with epilepsy, we summarised the current outcomes and measurement instruments used in completed phase III and IV clinical trials registered in the clinicaltrials.gov and International Standard Randomised Controlled Trial Number (ISRCTN) databases.

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Objectives: With a projected rise in care home residency and the disproportionate impact of epilepsy and seizures on older adults, understanding seizure-related needs in this population is crucial. Data silos and inconsistent recording of residence status make this challenging. We thus leveraged ambulance data to investigate seizure call-out incidence, characteristics, management and costs in care homes compared with the wider community.

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Ketyl radicals are valuable reactive intermediates because they allow carbonyl chemistry to be extended beyond traditional electrophilic reactivity through simple single-electron reduction to a nucleophilic radical. However, this pathway is challenging due to the large negative reduction potentials of carbonyls, thus requiring highly reducing conditions. Herein, we describe the development of an alternative strategy to access ketyl radicals from aldehydes, which avoids the reduction pathway by instead proceeding via single-electron oxidation and desulfination of α-hydroxy sulfinates.

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Background: Calls have been made for paramedics to have some form of care pathway that they could use to safely divert adults with epilepsy away from emergency departments and instigate ambulatory care improvements. Different configurations are possible. To know which to prioritise for implementation/evaluation, there is a need to determine which are acceptable to service users and likely National Health Service-feasible.

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Asymmetric diboration of terminal alkenes is well established, and subsequent selective functionalization of the less hindered primary boronic ester is commonly achieved. Conversely, selective functionalization of the sterically less accessible secondary boronic ester remains challenging. An alternative way to control chemoselective functionalization of bis(boron) compounds is by engendering different Lewis acidity to the two boryl moieties, since reactivity would then be dictated by Lewis acidity instead of sterics.

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C(sp)-rich heterocycles are privileged building blocks for pharmaceuticals and agrochemicals. Therefore, synthetic methods that provide access to novel saturated nitrogen-containing heterocycles are in high demand. Herein, we report a general synthesis of 1-azabicyclo[2.

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Purpose: With epilepsy increasingly affecting older adults, seizure-related care needs arise in new settings. Persons in these settings must receive optimal support and challenges identified for remediation. This may entail the epilepsy community researching in unfamiliar environments.

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With increasing interest in constructing more three-dimensional entities, there has been growing interest in cross-coupling reactions that forge C(sp)-C(sp) bonds, which leads to additional challenges as it is not just a more difficult bond to construct but issues of stereocontrol also arise. Herein, we report the stereocontrolled cross-coupling of enantioenriched boronic esters with racemic allylic carbonates enabled by iridium catalysis, leading to the formation of C(sp)-C(sp) bonds with single or vicinal stereogenic centers. The method shows broad substrate scope, enabling primary, secondary, and even tertiary boronic esters to be employed, and can be used to prepare any of the four possible stereoisomers of a coupled product with vicinal chiral centers.

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Introduction: To identify service users' preferences for an alternative care pathway for adults with epilepsy presenting to the ambulance service.

Methods: Extensive formative work (qualitative, survey and knowledge exchange) informed the design of a stated preference discrete choice experiment (DCE). This hypothetical survey was hosted online and consisted of 12 binary choices of alternative care pathways described in terms of: the paramedic's access to medical records/ 'care plan', what happens next (described in terms of conveyance), time, availability of epilepsy specialists today, general practitioner (GP) notification and future contact with epilepsy specialists.

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Introduction: Adults presenting to the ambulance service for diagnosed epilepsy are often transported to emergency departments (EDs) despite no clinical need. An alternative care pathway (CP) could allow paramedics to divert them from ED and instigate ambulatory care improvements. To identify the most promising CP configuration for subsequent testing, the COLLABORATE project surveyed people with epilepsy and family/friends who had recently used the English ambulance service to elicit preferences for 288 CP configurations for different seizures.

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Article Synopsis
  • Ambulance services face challenges when responding to suspected seizures, creating uncertainty for paramedics about whether to take patients to the emergency department.
  • The RADOSS project is creating a risk assessment tool to estimate the likelihood of negative outcomes after suspected seizures, aiming to improve decision-making for patient care.
  • Through workshops with stakeholders, important feedback led to the identification of 10 key variables for the tool, emphasizing that it should support clinicians rather than dictate care decisions.
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Enones are widely utilized linchpin functional groups in chemical synthesis and molecular biology. We herein report the direct conversion of boronic esters into enones using commercially available methoxyallene as a three-carbon building block. Following boronate complex formation by reaction of the boronic ester with lithiated-methoxyallene, protonation triggers a stereospecific 1,2-migration before oxidation generates the enone.

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Background: Paramedics convey a high proportion of seizure patients with no clinical need to emergency departments (EDs). In a landmark study, only 27% of UK paramedics reported being "Very…"/ "Extremely confident" making seizure conveyance decisions. Improved pre-registration education on seizures for paramedics is proposed.

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Carbon-phosphorus bond formation is significant in synthetic chemistry because phosphorus-containing compounds offer numerous indispensable biochemical roles. While there is a plethora of methods to access organophosphorus compounds, phosphonylations of readily accessible alkyl radicals to form aliphatic phosphonates are rare and not commonly used in synthesis. Herein, we introduce a novel phosphorus radical trap "BecaP" that enables facile and efficient phosphonylation of alkyl radicals under visible light photocatalytic conditions.

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Decarboxylative halogenation reactions of alkyl carboxylic acids are highly valuable reactions for the synthesis of structurally diverse alkyl halides. However, many reported protocols rely on stoichiometric strong oxidants or highly electrophilic halogenating agents. Herein, we describe visible-light photoredox-catalyzed decarboxylative halogenation reactions of N-hydroxyphthalimide-activated carboxylic acids that avoid stoichiometric oxidants and use inexpensive inorganic halide salts as the halogenating agents.

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Enantioenriched organoboron intermediates are important building blocks in organic synthesis and drug discovery. Recently, transition metal-catalyzed enantioselective 1,2-metalate rearrangements of alkenylboronates have emerged as an attractive protocol to access these valuable reagents by installing two different carbon fragments across C═C π-bonds. Herein, we report the development of an iridium-catalyzed asymmetric allylation-induced 1,2-metalate rearrangement of bicyclo[1.

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Borylations of inert carbon-hydrogen bonds are highly useful for transforming feedstock chemicals into versatile organoboron reagents. Catalysis of these reactions has historically relied on precious-metal complexes, which promote dehydrogenative borylations with diboron reagents under oxidant-free conditions. Recently, photoinduced radical-mediated borylations involving hydrogen atom transfer pathways have emerged as attractive alternatives because they provide complimentary regioselectivities and proceed under metal-free conditions.

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Article Synopsis
  • The synthesis of four-membered carbocycles, important for medicinal chemistry, has been enhanced through a new method for producing spirocyclic epoxides and aziridines with a cyclobutane structure.
  • A two-step one-pot reaction involves lithiating bicyclo[1.1.0]butyl sulfoxide and reacting it with carbonyl compounds followed by cross-coupling to create the desired products efficiently.
  • The resulting compounds are versatile and can undergo ring-opening reactions, making them useful building blocks for creating complex three-dimensional molecular structures.
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Article Synopsis
  • * Researchers present a simple method to create spirocyclic dihydropyridines by using a specific rearrangement process on 4-(1'-hydroxycyclobutyl)pyridines.
  • * The findings highlight opportunities for modifying the starting materials and using the resulting compounds, which may lead to faster creation of important medicinal spirocycles.
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The development of preparative methods for the synthesis of four-membered carbocycles is gaining increasing importance due to the widespread utility of cyclic compounds in medicinal chemistry. Herein, we report the development of a new methodology for the production of spirocyclic epoxides and aziridines containing a cyclobutane motif. In a two-step one-pot process, a bicyclo[1.

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Objective: To identify the views of people with epilepsy (PWE), and their significant others, on the repurposing and trialing of statins as a potential antiepileptogenic or disease-modifying treatment for those who have had the first seizure.

Methods: Online questionnaire. Participants needed to be aged ≥ 16 years, UK residents, and able to independently complete a questionnaire in English.

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Polyketide natural products often contain common repeat motifs, for example, propionate, acetate and deoxypropionate, and so can be synthesized by iterative processes. We report here a highly efficient iterative strategy for the synthesis of polyacetates based on boronic ester homologation that does not require functional group manipulation between iterations. This process involves sequential asymmetric diboration of a terminal alkene, forming a 1,2-bis(boronic ester), followed by regio- and stereoselective homologation of the primary boronic ester with a butenyl metallated carbenoid to generate a 1,3-bis(boronic ester).

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Background: A Core Outcome Set (COS) is a standardised list of outcomes that should be reported as a minimum in all clinical trials. In epilepsy, the choice of outcomes varies widely among existing studies, particularly in clinical trials. This diminishes opportunities for informed decision-making, contributes to research waste and is a barrier to integrating findings in systematic reviews and meta-analyses.

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Introduction: Ambulances services are asked to further reduce avoidable conveyances to emergency departments (EDs). Risk of Adverse Outcomes after a Suspected Seizure seeks to support this by: (1) clarifying the risks of conveyance and non-conveyance, and (2) developing a risk prediction tool for clinicians to use 'on scene' to estimate the benefits an individual would receive if conveyed to ED and risks if not.

Methods And Analysis: Mixed-methods, multi-work package (WP) project.

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