Electrochemical Late-Stage Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(19), P. 11269 - 11335

Published: Sept. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Language: Английский

---

Sulfilimines from a Medicinal Chemist’s Perspective: Physicochemical and in Vitro Parameters Relevant for Drug Discovery

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

While sulfoximines are nowadays a well established functional group for medicinal chemistry, the properties of sulfilimines significantly less studied, and no sulfilimine has progressed to clinic date. In this account, physicochemical in vitro reported compared those other more traditional groups. Furthermore, impact on real drug scaffolds is studied two series sulfilimine-containing analogs imatinib hNE inhibitors. We show that can be chemically configurationally stable under physiologically relevant conditions they basic highly polar thus often beneficial solubility metabolic stability, although at cost reduced permeability. conclude S-cyclopropyl,S-(hetero)aryl S,S-di(hetero)aryl so far neglected but potentially valuable S(IV) based pharmacophores deserve considered as part chemistry toolbox.

Language: Английский

---

A reagent to access methyl sulfones

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 29, 2025

A chemical reagent to access methyl sulfones has been developed. Its reaction with various bis-nucleophiles leads the rapid formation of previously unknown heteroaromatic sulfones. Analogous strategy can also be used construct alkyl-, CHF2-, CF3- and even bicyclo[1.1.1]pentane-containing derivatives. These compounds have demonstrated a high potential for use in medicinal chemistry coordination chemistry. Methyl sulfone is standard polar substituent found different agro chemicals or drugs but due lack convenient efficient approaches them, are less investigated. Here authors report

Language: Английский

---

Emerging Building Blocks for Medicinal Chemistry: Recent Synthetic Advances

European Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 2021(47), P. 6478 - 6510

Published: Sept. 8, 2021

Abstract Current medicinal chemistry relies heavily on the quality of building blocks, i. e. reagents used to introduce chemical diversity into target molecules. The last decade witnessed an emergence many novel (or well‐overlooked old) chemotypes for drug discovery, which is related adapting new synthetic methodologies, designing sp 3 ‐enriched bioisosteres, paying attention previously underrated even unwanted) structural motifs, or combination thereof. In this review with 532 references, a survey selected that emerged recently in provided, focus synthesis corresponding blocks. Thus, saturated (hetero)aliphatic boronates, sulfonyl fluorides, sulfinates, non‐classical benzene isosteres, bicyclic morpholine/piperidine/piperazine analogs, as well gem ‐difluorinated cycloalkanes (as example emerging fluorinated motifs) are discussed.

Language: Английский

---

N-Trifluoromethyl Amines and Azoles: An Underexplored Functional Group in the Medicinal Chemist’s Toolbox

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(21), P. 13076 - 13089

Published: Oct. 28, 2020

Introducing trifluoromethyl groups is a common strategy to improve the properties of biologically active compounds. However, N-trifluoromethyl moieties on amines and azoles are very rarely used. To evaluate their suitability in drug design, we synthesized series azoles, determined stability aqueous media, investigated properties. We show that prone hydrolysis, whereas have excellent stability. Compared N-methyl analogues, higher lipophilicity can increased metabolic Caco-2 permeability. Furthermore, serve as bioisosteres N-iso-propyl N-tert-butyl azoles. Consequently, suggest valuable substructures be considered medicinal chemistry.

Language: Английский

---

Electrochemical C–H phosphorylation of arenes in continuous flow suitable for late-stage functionalization

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 16, 2021

Abstract The development of efficient and sustainable methods for carbon-phosphorus bond formation is great importance due to the wide application organophosphorus compounds in chemistry, material sciences biology. Previous C–H phosphorylation reactions under nonelectrochemical or electrochemical conditions require directing groups, transition metal catalysts, chemical oxidants suffer from limited scope. Herein we disclose a catalyst- external oxidant-free, reaction arenes continuous flow synthesis aryl phosphorus compounds. C–P formed through with anodically generated P-radical cations, class reactive intermediates remained unexplored despite intensive studies P-radicals. high reactivity cations coupled mild electrosynthesis ensures not only diverse electronic properties but also selective late-stage functionalization complex natural products bioactive synthetic utility method further demonstrated by production 55.0 grams one phosphonate products.

Language: Английский

---

A Close-up Look at the Chemical Space of Commercially Available Building Blocks for Medicinal Chemistry

Journal of Chemical Information and Modeling, Journal Year: 2021, Volume and Issue: 62(9), P. 2171 - 2185

Published: Dec. 20, 2021

The ability to efficiently synthesize desired compounds can be a limiting factor for chemical space exploration in drug discovery. This is conditioned not only by the existence of well-studied synthetic protocols but also availability corresponding reagents, so-called building blocks (BBs). In this work, we present detailed analysis 400 000 purchasable BBs. was defined synthons─fragments contributed final molecules upon reaction. They allow an BB physicochemical properties and diversity, unbiased leaving protective groups actual reagents. main classes BBs were analyzed terms their availability, rule-of-two-defined quality, diversity. Available eventually compared reference set biologically relevant synthons derived from ChEMBL fragmentation, order illustrate how well they cover medicinal chemistry needs. performed on newly constructed universal generative topographic map synthon that enables visualization both libraries overlapped library-specific regions.

Language: Английский

---

Asymmetric Hydrophosphinylation of Alkynes: Facile Access to Axially Chiral Styrene‐Phosphines

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(3)

Published: Nov. 25, 2022

Abstract A Cu/CPA co‐catalytic system has been developed for achieving the direct hydrophosphinylation of alkynes with phosphine oxides in delivering novel axially chiral phosphorus‐containing alkenes high yields and excellent enantioselectivities (up to 99 % yield ee). DFT calculations were performed elucidate reaction pathway origin enantiocontrol. This streamlined modular methodology establishes a new platform design application styrene‐phosphine ligands.

Language: Английский

---

Visible-Light-Induced Redox-Neutral Difunctionalization of Alkenes and Alkynes

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(72), P. 9659 - 9691

Published: Jan. 1, 2024

The twelve principles of green chemistry illuminate the pathway in direction sustainable and eco-friendly synthesis, marking a fundamental shift synthetic organic paradigms. In this realm, harnessing power visible light for difunctionalization various skeletons without employing any external oxidant or reductant, specifically termed as redox-neutral difunctionalization, has attracted tremendous interest from chemists due to its low cost, easy availability environmentally friendly nature contrast traditional metal-catalyzed difunctionalizations. This review presents an overview recent updates on visible-light-induced reactions with literature coverage up May 2024.

Language: Английский

---

Design and Synthesis of Sulfanilamide Aminophosphonates as Novel Antibacterial Agents towards Escherichia coli

Chinese Journal of Chemistry, Journal Year: 2021, Volume and Issue: 39(8), P. 2251 - 2263

Published: May 1, 2021

Main observation and conclusion The limit ability of traditional antibiotics to treat drug resistant bacteria calls for new therapeutic alternatives. A class unique sulfanilamide aminophosphonates as potential agents against microbes was synthesized by one‐pot three‐component reaction. Noticeably, fluorobenzyl derivative 5d (MIC = 2 μg/mL) active E. coli infection exerted no obvious toxicity towards human mammalian cells. Compound also displayed good anti‐biofilm activity low possibility induce resistance. Mechanism investigation elucidated that molecule could disrupt membrane through generation reactive oxygen (ROS) then intercalate into deoxyribonucleic acid (DNA) form a steady 5d‐DNA complex, which led bacterial death. These results indicated would shed light on developing novel antibacterial agents.

Language: Английский

---