233 research outputs found
Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis.
The use of photochemical transformations is a powerful strategy that allows for the formation of a high degree of molecular complexity from relatively simple building blocks in a single step. A central feature of all light-promoted transformations is the involvement of electronically excited states, generated upon absorption of photons. This produces transient reactive intermediates and significantly alters the reactivity of a chemical compound. The input of energy provided by light thus offers a means to produce strained and unique target compounds that cannot be assembled using thermal protocols. This review aims at highlighting photochemical transformations as a tool for rapidly accessing structurally and stereochemically diverse scaffolds. Synthetic designs based on photochemical transformations have the potential to afford complex polycyclic carbon skeletons with impressive efficiency, which are of high value in total synthesis.R01 GM073855 - NIGMS NIH HHS; R01 GM096129 - NIGMS NIH HHS; R35 GM118173 - NIGMS NIH HH
NOVEL CASCADE REACTIONS OF ALKENYLZIRCONOCENES AND THEIR APPLICATION TO THE SYNTHESIS OF CYCLOPROPYL PEPTIDE MIMETICS
We have successfully applied to ZrâZn methodology developed in the Wipf group to the preparation of functionalized allylic amides and alcohols via the 1,2-addition to imines and α-keto esters. During the preparation of allylic amides, concomitant formation of C-cyclopropylalkylamides was observed in CHâClâ. The combination of the ZrâZn methodology with the Simmons-Smith cyclopropanation reaction has led to the discovery of a novel cascade reaction for the preparation of C,C-dicyclopropylmethylamides from simple, readily available starting materials. These functionalized amides have served as precursors in a diversity-oriented approach for the preparation of 7-, 8-, and 9-membered azaspirocyclic ring structures based on reductive amination, epoxide opening or ring-closing metathesis strategies. Finally, a small library of α,ÎČ-cyclopropyl-Îł-amino acids were prepared in 6-7 steps from readily available starting materials and evaluated for their potential as peptide mimetics. Simple amide derivatives were found to adopt stable sheet-like structures in the solid state, whereas the structural properties of oligopeptides were not readily assessed using crystallographic techniques. A combination of molecular modeling, circular dichroism and NMR studies was used to ascertain the solution folding preferences of our novel peptides
Opportunities in Photocatalytic Synthesis
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108661/1/2739_ftp.pd
Visible Light Mediated Aryl Migration by Homolytic CâN Cleavage of Aryl Amines
The photocatalytic preparation of aminoalkylated heteroarenes from haloalkylamides via a 1,4âaryl migration from nitrogen to carbon, conceptually analogous to a radical Smiles rearrangement, is reported. This method enables the substitution of amino groups in heteroaromatic compounds with aminoalkyl motifs under mild, iridium(III)âmediated photoredox conditions. It provides rapid access to thienoazepinone, a pharmacophore present in multiple drug candidates for potential treatment of different conditions, including inflammation and psychotic disorders.Aminoalkylated heteroarenes are synthesized by a radical Smiles rearrangement of haloalkylamides through a key CâN cleavage under mild, iridium(III)âmediated photoredox conditions. The method provides rapid access to the pharmaceutically relevant thienoazepinone scaffold.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/1/anie201806659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/2/anie201806659.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146419/3/anie201806659-sup-0001-misc_information.pd
Radical CarbonâCarbon Bond Formations Enabled by Visible Light Active Photocatalysts
This mini-review highlights the Stephenson group's contribution to the field of photoredox catalysis with emphasis on carbonâcarbon bond formation. The realization of photoredox mediated reductive dehalogenation initiated investigations toward both intra- and intermolecular coupling
reactions. These reactions commenced via visible light-mediated reduction of activated halogens to give carbon-centered radicals that were subsequently involved in carbonâcarbon bond forming transformations. The developed protocols using Ru and Ir based polypyridyl complexes as
photoredox catalysts were further tuned to efficiently catalyze overall redox neutral atom transfer radical addition reactions. Most recently, a simplistic flow reactor technique has been utilized to affect a broad scope of photocatalytic transformations with significant enhancement in reaction
efficiency
Exploiting Imine Photochemistry for Masked NâCentered Radical Reactivity
This report details the development of a masked Nâcentered radical strategy that harvests the energy of light to drive the conversion of cyclopropylimines to 1âaminonorbornanes. This process employs the Nâcentered radical character of a photoexcited imine to facilitate the homolytic fragmentation of the cyclopropane ring and the subsequent radical cyclization sequence that forms two new CâC bonds en route to the norbornane core. Achieving bondâforming reactivity as a function of the Nâcentered radical character of an excited state Schiff base is unique, requiring only violet light in this instance. This methodology operates in continuous flow, enhancing the potential to translate beyond the academic sector. The operational simplicity of this photochemical process and the structural novelty of the (hetero)arylâfused 1âaminonorbornane products are anticipated to provide a valuable addition to discovery efforts in pharmaceutical and agrochemical industries.The Nâcentered openâshell character of photoexcited cyclopropylimines is utilized to initiate a radical fragmentationâcyclization sequence that generates bridgeheadâfunctionalized norbornanes. This unique mode of reactivity requires only violet light to proceed, and the 1âaminonorbornane products are valuable building blocks for drug and agrochemical discovery programs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153143/1/anie201909492_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153143/2/anie201909492.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153143/3/anie201909492-sup-0001-misc_information.pd
The importance of data issues when comparing cystic fibrosis registry outcomes between countries : are annual review FEV1 in the UK only collected when subjects are well?
Rationale, aims and objective
Crossâcountry comparisons of cystic fibrosis (CF) outcomes can potentially identify variation in care but are dependent on data quality. An important assumption is that the UK annual review FEV1 is only collected during periods of clinical stability. If this assumption does not hold, results of FEV1 comparisons may be biased in favour of registries with encounterâbased FEV1. We aimed to test the assumption that CF annual reviews in the UK are only performed during periods of clinical stability.
Method
Prospective encounterâbased data collected in Sheffield (n = 174) was used to establish whether annual review FEV1 were always collected during periods of clinical stability and to determine the groupâlevel discrepancy between annual review vs best FEV1. We then went on to quantify the groupâlevel discrepancy between annual review and best annual FEV1 readings within the UK registry (n = 2995) to determine if the differences observed in Sheffield also apply to the wider UK data.
Results
Sheffield results showed a groupâlevel discrepancy between best and annual review FEV1 of â2.5% (95% CI â3.95% to â1.2%) for annual reviews performed during periods of clinical stability (n = 50). The groupâlevel discrepancy is larger at â8.0% (95% CI â11.2% to â4.9%) among annual reviews performed during periods of clinical instability (n = 13). Therefore, the magnitude of this groupâlevel discrepancy is a surrogate for the proportion of clinically stable annual reviewsâsmaller discrepancy indicates a higher proportion of clinically stable annual reviews and vice versa.
The overall groupâlevel discrepancy in the UK registry (â5.6%, 95% CI â5.9 to â5.4%) was similar to Sheffield (â6.1%, 95% CI â7.1 to â5.1%). Around 20% of the clinician reviewed, annual reviews in Sheffield were performed during periods of clinically instability.
Conclusions
Annual review FEV1 underestimates lung health of adults with CF in the UK and may bias crossâcountry comparisons
Arylmigration durch sichtbares Licht unter homolytischer CâNâSpaltung in Arylaminen
Die photokatalytische Synthese von aminoalkylierten Heteroaromaten aus Halogenalkylamiden gelingt durch die einer SmilesâUmlagerung konzeptionell analogen 1,4âArylmigration von Stickstoff zu Kohlenstoff. Mit dieser neuartigen Methode kann die Substitution von Aminogruppen in Heteroaromaten durch Aminoalkylmotive unter milden, Iridium(III)âvermittelten PhotoredoxâBedingungen realisiert werden. Sie bietet einen schnellen Zugang zum ThienoazepinonâBicyclus, einem Pharmakophor, der in unterschiedlichen Verbindungen mit potentiellen Anwendungen bei der Behandlung von bestimmten EntzĂŒndungen und psychischen Krankheiten vorkommt.Aminoalkylierte Heteroarene werden durch SmilesâUmlagerung von Halogenalkylamiden ĂŒber eine CâNâSpaltung unter milden, Iridium(III)âvermittelten PhotoredoxâBedingungen synthetisiert. Das Verfahren bietet einen schnellen Zugang zu dem pharmazeutisch relevanten ThienoazepinonâGrundgerĂŒst.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146369/1/ange201806659.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146369/2/ange201806659_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146369/3/ange201806659-sup-0001-misc_information.pd
A Scalable Biomimetic Synthesis of Resveratrol Dimers and Systematic Evaluation of their Antioxidant Activities
An efficient synthetic route to the resveratrol oligomers quadrangularinâ
A and pallidol is reported. It features a scalable biomimetic oxidative dimerization that proceeds in excellent yield and with complete regioselectivity. A systematic evaluation of the natural products and their synthetic precursors as radicalâtrapping antioxidants has revealed that, contrary to popular belief, this mode of action is unlikely to account for their observed biological activity.HartnĂ€ckigkeit zahlt sich aus: Eine kurze Synthese der ResveratrolâOligomere Quadrangularinâ
A und Pallidol macht sich die StabilitĂ€t der von 2,6âDiâtertâbutylphenol abgeleiteten Radikalâ und der ChinonmethidâZwischenstufe zunutze. Untersuchungen dieser Verbindungen als antioxidative RadikalfĂ€nger ergaben, dass diese Eigenschaft höchstwahrscheinlich nicht die Ursache ihrer beobachteten biologischen AktivitĂ€t ist.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110868/1/3825_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/110868/2/ange_201409773_sm_miscellaneous_information.pd
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