Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(2), P. 2017 - 2291

Published: Nov. 23, 2021

We present here a review of the photochemical and electrochemical applications multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis. MS-PCETs are redox mechanisms which both an proton exchanged together, often concerted elementary step. As such, MS-PCET can function as non-classical mechanism for homolytic bond activation, providing opportunities to generate synthetically useful free radical intermediates directly from wide variety common functional groups. introduction practitioner’s guide reaction design, with emphasis on unique energetic selectivity features that characteristic this class. then chapters oxidative N–H, O–H, S–H, C–H homolysis methods, generation corresponding neutral species. Then, reductive PCET activations involving carbonyl, imine, other X═Y π-systems, heteroarenes, where ketyl, α-amino, heteroarene-derived radicals be generated. Finally, we asymmetric catalysis materials device applications. Within each chapter, subdivide by group undergoing homolysis, thereafter type transformation being promoted. Methods published prior end December 2020 presented.

Language: Английский

---

The importance of sulfur-containing motifs in drug design and discovery

Expert Opinion on Drug Discovery, Journal Year: 2022, Volume and Issue: 17(5), P. 501 - 512

Published: Feb. 23, 2022

Sulfur-containing functional groups are privileged motifs that occur in various pharmacologically effective substances and several natural products. Various functionalities found with a sulfur atom at diverse oxidation states, as illustrated by thioether, sulfoxide, sulfone, sulfonamide, sulfamate, sulfamide functions. They valuable scaffolds the field of medicinal chemistry part large array approved drugs clinical candidates.Herein, authors review current research on development organosulfur-based drug discovery. This article also covers details their roles new lead compounds reported literature over past five years 2017-2021.Given its prominent role importance discovery, has attracted continuing interest been used design demonstrate variety biological pharmacological feature activities. Overall, sulfur's continues to grow. However, many remain underused small-molecule discovery deserve special attention armamentarium for treating diseases. Research efforts still required synthetic methodology direct access these functions late-stage functionalization.

Language: Английский

---

Synthesis and Transformations of NH‐Sulfoximines

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(69), P. 17293 - 17321

Published: Sept. 14, 2021

Recent years have seen a marked increase in the occurrence of sulfoximines chemical sciences, often presented as valuable motifs for medicinal chemistry. This has been prompted by both pioneering works taking sulfoximine containing compounds into clinical trials and concurrent development powerful synthetic methods. review covers recent developments synthesis concentrating on since 2015. includes extensive S-N S-C bond formations. Flow chemistry processes are also covered. Finally, subsequent transformations sulfoximines, particularly N-functionalization reviewed, including N-S, N-P, N-C forming cyclization reactions.

Language: Английский

---

Synthesis of chiral sulfinate esters by asymmetric condensation

Nature, Journal Year: 2022, Volume and Issue: 604(7905), P. 298 - 303

Published: Feb. 14, 2022

Language: Английский

---

Catalytic Enantioselective Sulfur Alkylation of Sulfenamides for the Asymmetric Synthesis of Sulfoximines

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(39), P. 17808 - 17814

Published: Sept. 26, 2022

Sulfoximines are increasingly incorporated in agrochemicals and pharmaceuticals, with the two enantiomers of chiral sulfoximines often having profoundly different binding interactions biomolecules. Therefore, their application to drug discovery development requires challenging preparation single rather than racemic mixtures. Here, we report a general fundamentally new asymmetric synthesis sulfoximines. The first S-alkylation sulfenamides, which readily accessible sulfur compounds one carbon nitrogen substituent, represents key step. A broad scope for was achieved by rhodium-catalyzed coupling diazo under mild conditions. When rhodium catalyst utilized loadings as low 0.1 mol %, products were obtained high yields enantiomeric ratios up 98:2 at newly generated center. efficiently converted variety complete retention stereochemistry. utility this approach further demonstrated complex sulfoximine agrochemical.

Language: Английский

---

Applications of Bioisosteres in the Design of Biologically Active Compounds

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(47), P. 18087 - 18122

Published: March 24, 2023

The design of bioisosteres represents a creative and productive approach to improve molecule, including by enhancing potency, addressing pharmacokinetic challenges, reducing off-target liabilities, productively modulating physicochemical properties. Bioisosterism is principle exploited in the bioactive compounds interest both medicinal agricultural chemists, this review, we provide synopsis applications where kind molecular editing has proved be advantageous molecule optimization. examples selected for discussion focus on carboxylic acids, fluorine fluorinated motifs compound design, some sulfoximine functionality, drug-H2O complexes, phenyl ring.

Language: Английский

---

Cobalt(III)/Chiral Carboxylic Acid‐Catalyzed Enantioselective Synthesis of Benzothiadiazine‐1‐oxides via C−H Activation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(28)

Published: May 2, 2022

Abstract Among sulfoximine derivatives containing a chiral sulfur center, benzothiadiazine‐1‐oxides are important for applications in medicinal chemistry. Here, we report that the combination of an achiral cobalt(III) catalyst and pseudo‐ C 2 ‐symmetric H 8 ‐binaphthyl carboxylic acid enables asymmetric synthesis from sulfoximines dioxazolones via enantioselective C−H bond cleavage. With optimized protocol, with several functional groups can be accessed high enantioselectivity.

Language: Английский

---

New Opportunities for the Utilization of the Sulfoximine Group in Medicinal Chemistry from the Drug Designer's Perspective**

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(56)

Published: July 5, 2022

Extension of the medicinal chemistry toolbox is in vital interest drug designers. However, diffusion an innovation can be a lengthy process. Along these lines, it took almost 70 years before use sulfoximine group reached critical mass chemistry. Even though this versatile functional has increased exponentially recent years, there ample room for further innovative applications. This Review highlights emerging trends and opportunities designers utilization chemistry, such as construction complex molecules, proteolysis targeting chimeras (PROTACs), antibody-drug conjugates (ADCs) novel warheads covalent inhibition.

Language: Английский

---

Synthesis of Chiral Sulfonimidoyl Chloride via Desymmetrizing Enantioselective Hydrolysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5439 - 5446

Published: Feb. 22, 2023

Direct construction of chiral S(VI) from prochiral S(II) is a formidable challenge due to the inevitable formation stable S(IV). Previous synthetic strategies rely on conversion S(IV) or enantioselective desymmetrization preformed symmetrical substrates. Here, we report desymmetrizing hydrolysis in situ-generated symmetric aza-dichlorosulfonium sulfenamides for preparation sulfonimidoyl chlorides, which could be used as general synthon obtaining series derivatives.

Language: Английский

---

Asymmetric Synthesis of S(IV) and S(VI) Stereogenic Centers

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 700 - 714

Published: Feb. 28, 2023

Sulfur can form diverse S(IV) and S(VI) stereogenic centers, of which some have gained significant attention recently due to their increasing use as pharmacophores in drug discovery programs. The preparation these sulfur centers enantiopure has been challenging, progress made will be discussed this Perspective. This Perspective summarizes different strategies, with selected works, for asymmetric synthesis moieties, including diastereoselective transformations using chiral auxiliaries, enantiospecific compounds, catalytic enantioselective synthesis. We discuss the advantages limitations strategies provide our views on how field develop.

Language: Английский

---