Photolytic Access to Oxaspirodecanes and Chromenes from Vinyldiazo Ester Cycloaddition with p-Quinones: A Vinylcarbene Is Not Involved

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

Synthetic methods that provide access to skeletally diverse heterocyclic motifs are poised accelerate drug discovery and streamline the synthesis of advanced intermediates materials. However, development such synthetic necessitates leveraging previously unexplored mechanistic pathways. We report herein an efficient blue light-emitting diode light-induced reaction vinyldiazoacetates quinones produces spirocyclic dihydrofurans, featuring synthetically challenging oxaspiro[4,5]decane core numerous medicinal agents, agrochemicals, natural products. In a departure from well-established photochemical reactivity diazo compounds, these reactions do not involve vinylcarbene formed by photolytic dinitrogen extrusion. Instead, they result photoexcitation quinone its triplet state with subsequent energy transfer vinyldiazo ester. The addition vinylogous carbon vinyldiazoacetate oxygen affords diradical collapses dihydrofuran upon loss dinitrogen. A strain release-driven Bro̷nsted acid-catalyzed rearrangement products unravels fused bicyclic ring system equally medicinally valuable chromenes, enabling facile skeletal diversification important motifs.

Язык: Английский

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Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

The cell surface proteome, or surfaceome, is the hub for cells to interact and communicate with outside world. Many disease-associated changes are hard-wired within yet approved drugs target less than 50 proteins. In past decade, proteomics community has made significant strides in developing new technologies tailored studying surfaceome all its complexity. this review, we first dive into unique characteristics functions of emphasizing necessity specialized labeling, enrichment, proteomic approaches. An overview surfaceomics methods provided, detailing techniques measure protein expression how leads novel discovery. Next, highlight advances proximity labeling (PLP), showcasing various enzymatic photoaffinity can map protein-protein interactions membrane complexes on surface. We then review role extracellular post-translational modifications, focusing glycosylation, proteolytic remodeling, secretome. Finally, discuss identifying tumor-specific peptide MHC they have shaped therapeutic development. This emerging field neo-protein epitopes constantly evolving, where targets identified at proteome level encompass defined PTMs, complexes, dysregulated cellular tissue locations. Given functional importance biology therapy, view as a critical piece quest neo-epitope

Язык: Английский

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From Structure to Function: Designing Iridium Catalysts with Spin-Forbidden Excitation for Low-Energy Light-Driven Reactions

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Herein we describe a comprehensive study of ligand effects on optoelectronic properties series Ir(III) catalysts which undergo formally spin-forbidden excitation using low-energy light. We demonstrate that electronic and steric tuning several variables can be explained by their impact the HOMO LUMO energies complex. Density functional theory calculations catalysts' adiabatic triplet agree with experimental results to within 0.05 eV average. As many these subtle are independent each other, merger them in single complex tends have an additive effect thus succeeded developing family highly oxidizing iridium photocatalysts operate excitation.

Язык: Английский

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Red-Light-Induced Cysteine Modifications Suitable for Protein Labeling

ACS Organic & Inorganic Au, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Язык: Английский

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Facile Access to Hindered Ethers via Photoinduced O–H Bond Insertions

ACS Central Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

The synthesis of the hindered and polyfluorinated dialkyl ethers poses challenges owing to bulkiness tertiary alcohols low nucleophilicity alcohols. Additionally, associated competitive side reactions always provide poor reactivities. Although certain strategies, such as electrocatalytic decarboxylation hydroalkoxylation, have been explored, a straightforward method for obtaining with structural diversity remains elusive. In this study, we exploited photoinduced approach that involves in situ formation singlet carbenes followed by O-H insertions access congested or Moreover, other nucleophiles phenols, H2O, thiols, silanols, tributyltin hydride, etc., are also tolerable obtain valuable products. gram-scale marketed drugs modification complex molecules demonstrate practicality approach. detailed mechanistic studies elucidated key intermediates reaction mechanism, which were distinct from traditional metal-carbenoid insertions.

Язык: Английский

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Subcellular Photocatalysis Enables Tumor-Targeted Inhibition of Thioredoxin Reductase I by Organogold(I) Complexes

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Selective inhibition of TrxR1 over TrxR2 is a highly sought-after goal, because the two enzymes play distinct roles in cancer progression. However, achieving targeted challenging due to their high homology and identical active site sequence. Herein we report new subcellular photocatalysis approach for by controllably activating organogold(I) prodrugs within cytosol, exclusive location TrxR1. The NHC-Au(I)-alkynyl complexes are stable evenly distributed cell; they can meanwhile be efficiently transformed into NHC-Au(I)-L species (L = labile ligands) via radical mechanism photocatalysts released cytosol (from endosome/lysosome) upon light irradiation, leading selective without affecting TrxR2. This results strong cytotoxicity cells with much higher selectivity than auranofin, pan TrxR inhibitor that cannot discriminate TrxR1/2, along potent antitumor activities multiple zebrafish mouse models. prodrug activation may thus suggest novel precision targeting using remarkable spatial control photocatalysis.

Язык: Английский

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Red Light and Supersilane: A Novel Pathway for Hydrofunctionalizations and Giese Reactions

ACS Organic & Inorganic Au, Год журнала: 2025, Номер unknown

Опубликована: Май 10, 2025

Язык: Английский

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Total Synthesis of (±)-Rhazinilam via Red-Light-Driven Zinc(II)porphyrin-Catalyzed Radical Cyclization of N-Substituted Pyrrole

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Май 27, 2025

A red-light-driven radical cyclization strategy has been developed for the concise synthesis of (±)-rhazinilam. The transformation, catalyzed by [5,15-bis(pentafluorophenyl)-10,20-diphenylporphinato]zinc(II), enables efficient formation a tetrahydroindolizine core from an N-acyloxyphthalimide-substituted pyrrole, providing key intermediate en route to target alkaloid.

Язык: Английский

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Mechanistic Insights: Correspondence on “Tuning Co‐Operative Energy Transfer in Copper(I) Complexes Using Two‐Photon Absorbing Diimine‐Based Ligand Sensitizers”

Angewandte Chemie International Edition, Год журнала: 2025, Номер unknown

Опубликована: Июнь 1, 2025

Abstract In a recent communication, Collins and coworkers presented Cu(I) complex with photocatalytic activity under red light LED conditions, mainly for singlet oxygen‐driven reactions. Guided by steady‐state emission measurements 800 nm excitation, the authors suggested that underlying mechanism generation of photoexcited key species is simultaneous two‐photon absorption via virtual state. However, such requires pulsed laser excitation cannot compete when conventional one‐photon also feasible selected wavelength range. Using several spectroscopic techniques reactivity assays different color intensity we unambiguously demonstrate followed rather inefficient oxygen (quantum yield <5%) responsible observed photoreactivity complex. addition, briefly summarize general mechanistic considerations, estimate typical photon densities required variety mechanisms, highlight importance optical filters impurities to avoid artifacts in spectra, present some guidelines differentiation between one‐ mechanisms.

Язык: Английский

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Mechanistic Insights: Correspondence on “Tuning Co‐Operative Energy Transfer in Copper(I) Complexes Using Two‐Photon Absorbing Diimine‐Based Ligand Sensitizers”

Angewandte Chemie, Год журнала: 2025, Номер unknown

Опубликована: Июнь 1, 2025

Abstract In a recent communication, Collins and coworkers presented Cu(I) complex with photocatalytic activity under red light LED conditions, mainly for singlet oxygen‐driven reactions. Guided by steady‐state emission measurements 800 nm excitation, the authors suggested that underlying mechanism generation of photoexcited key species is simultaneous two‐photon absorption via virtual state. However, such requires pulsed laser excitation cannot compete when conventional one‐photon also feasible selected wavelength range. Using several spectroscopic techniques reactivity assays different color intensity we unambiguously demonstrate followed rather inefficient oxygen (quantum yield <5%) responsible observed photoreactivity complex. addition, briefly summarize general mechanistic considerations, estimate typical photon densities required variety mechanisms, highlight importance optical filters impurities to avoid artifacts in spectra, present some guidelines differentiation between one‐ mechanisms.

Язык: Английский

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