Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• ], requires the presence of a nucleophile at the β-position of the amino acid and occurs exclusively on select amino acids. Specifically, cyclodehydration of a serine or threonine (followed by oxidation or reduction) generates an oxazole, oxazoline, or oxazolidine moiety in the NRP backbone, and the analogous

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• . Keywords: C–H functionalization; oxidation; peroxidation; radical reactions; TBHP; Introduction Organic peroxides are used in many different areas of human activities. The traditional and most developed field is the use of peroxides as initiators in the polymerization process for the production of a wide

• formation of peroxide 9. The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) [43]. Studying the oxidation of α-pinene (12

• then reacts with tert-butylperoxy radical B to form the target peroxide 20 and Cu(I). Cu(I) is oxidized by TBHP to form Cu(II) and tert-butoxy radical C, which abstracts a hydrogen atom from TBHP to form tert-butylperoxy radical B. Radical B can also be formed via oxidation of TBHP by complex A or the

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• ]. Beyond their essential biological roles, porphyrins and their derivatives are employed in a number of applications, acting as catalysts in numerous reactions, including oxidation, reduction, and cycloaddition [6][7][8][9][10]. Particularly when electron-rich porphyrins act as reducing agents, e.g. in

• to serve as a proton source for redox reactions at the metal. 3. The electronic properties of the porphyrin, especially the low oxidation potential, should not be increased. We have chosen four-fold meso-3,4,5-trimethoxyphenyl-substituted Ni porphyrin as the electron-rich system, however, the post

• carboxylic acids [10]. It was therefore obvious to use a perfluoroalkyl chain as a tether. However, a perfluoroalkyl chain as a substituent on the porphyrin has an electron-withdrawing effect and thus a negative influence on the oxidation potential. We have therefore inserted an O–CH2 group between the

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• reversible oxidation waves as shown from the CV data (Figure 6 and Table 1). This reversibility is crucial for the regeneration of dyes following redox processes. The compounds display ionisation energies (IEs) of −5.38 eV, −5.34 eV, and −5.40 eV for 3a, 3b, and 3c, respectively, with electron affinities

• exhibit a narrow HOMO–LUMO gap (1.46–1.47 eV), with a wide absorption range exceeding 800 nm compared to their previously reported precursors [30]. The electrochemical studies of the three materials show reversible oxidation and reduction waves with EA values that are in a similar range (from −3.70 to

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• state, eosin Y*. This excited state further undergoes oxidation via a single-electron-transfer (SET) reaction with Ar2IBF4 26, producing eosin Y+ and a phenyl radical 30 (Scheme 10). The radical intermediate 30 selectively binds to the C2 position of either quinoline or pyridine N-oxide, forming

• assist in the deprotonation of intermediate II to produce final products 27, while K2S2O8 aids in the oxidation of the photocatalyst in the case of pyridine N-oxide. In another photoinduced reaction procedure, Murarka et al. reported the formation of aryl radicals from a tetrameric electron donor

• 62. Acetonitrile was identified as a suitable solvent for this reaction, resulting in moderate to good yields of the products. The three main steps in the reaction were oxidation of the aryl iodide, addition of the TMP auxiliary, and C–O coupling reaction. Olofsson et al. worked towards the synthesis

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• oxidation with CrO3. Although this approach allowed for the synthesis of acceptor-substituted isatin-N-glycosides, it proved to be tedious and the yields were low. In a similar way, acetyl-protected isoindigo-N-glycosides were prepared. In addition, benzyl-protected isoindigo-N-glycoside β-58d, containing a

• of rhamnose with indoline (66) afforded β-67a which was transformed to indol-N-rhamnoside β-68a (Scheme 39) [59]. Benzylation and subsequent oxidation gave isatin-N-rhamnoside β-70a, albeit, in low yield. Condensation with 2-coumaranone (63) afforded the benzylated oxoisoindigo-N-rhamnoside β-71a

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• in Vm was caused by some modification – most likely oxidation – of the plasma membrane by the photoexcited triad molecule. Taken together, for the realization of rapid control of Vm using such C60-based molecules in the membrane, the suppression of ROS generation is an important consideration. In

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of N-aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which

• reacts with an isocyanide and an electron-rich aniline in a three-component Ugi-type reaction to give an α-aminoamidine. This compound might undergo an additional visible light-mediated oxidation to furnish a second iminium intermediate, which acts as electrophile in an intramolecular electrophilic

• : isocyanide; multicomponent reactions; one-pot reaction; oxidation; spiroindolenine; Ugi reaction; visible light; Introduction Diversity-oriented synthesis (DOS) is a successful approach to biologically active scaffolds directed to create an enormous exploratory space in pharmaceutical hit discovery [1][2

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• -dihydro-1H-pyrroles using aryldiazonium salts and (S)-PyraBox, followed by sequential Jones oxidation. They showcased their methodology by preparing both (R)-rolipram and (R)-baclofen hydrochloride. Tóth et al. reported the design and synthesis of new analogues of HeE1-2Tyr, a nonnucleoside SARS-CoV-2

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• , Trombay, Mumbai-400085, India Homi Bhabha National Institute, Anushaktinagar, Mumbai, PIN-400094, India 10.3762/bjoc.20.223 Abstract A transition-metal-free decarbonylation–oxidation protocol for the conversion of 3-arylbenzofuran-2(3H)-ones to 2-hydroxybenzophenones under mild conditions has been

• abilities has been verified by mathematical calculations. Keywords: decarbonylation–oxidation; hydroperoxide; 2-hydroxybenzophenone; transition-metal-free; UV-protection; Introduction Benzophenone compounds are ubiquitous in nature, and show biological activities such as anti-inflammatory, antiviral, and

• oxidative coupling of salicylaldehyde with arylboronic acids to successfully produce 2-hydroxybenzophenones [14]. Recently, a Ni-catalyzed decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones emerged as an innovative route to access 2-hydroxybenzophenones [2]. The use of transition metals poses

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• hydrogen bonding, although generally not dominant, can influence the complex formation as well [5]. Cyclodextrins form inclusion complexes with polar and non-polar substances of various aggregate states. This incredible versatility, combined with the enhanced stability against oxidation, as well as

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• -hydroxy-6-methyluracil, etc.). One of the successful methods for hydroxylation is peroxydisulfate oxidation. By modifying the Elbs reaction through catalysis and the introduction of additional oxidants, we have been able to significantly increase the yields of practically useful compounds. Keywords

• : oxidation; 6-methyluracil; peroxydisulfate; phthalocyanine catalysts; pyridine; Introduction The Elbs and Boyland–Sims peroxydisulfate oxidation reactions offer a convenient means of introducing the hydroxy function into phenols and aromatic amines [1]. The oxidation of phenol using peroxydisulfate was

• first demonstrated by Karl Elbs in 1893 [2], with E. Boyland later expanding this reaction to include aromatic amines [3]. Concurrently, the successful oxidation of several pyrimidine derivatives was also reported [4]. Since then, the reaction has been extensively researched on various classes of

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• pharmaceutical drugs and natural products. We classify these advancements into three types: anodic oxidation, cathodic reduction, and paired electrolysis (Figure 1). This review considers direct electrolysis (oxidation or reduction), mediator-induced electrolysis, and metal-catalyzed and photocatalyzed

• . Review 1 LSF via anodic oxidation To date, the majority of electrosynthetic methods in organic chemistry consists of anodic oxidations. These techniques are generally more robust and can often be performed outside of a glovebox, making them particularly attractive for larger scale applications in

• industrial settings. An anodic oxidation is frequently employed for C–H functionalization, which can simplify late-stage functionalization strategies. Additionally, many of these synthetic methods do not require precious metals, enhancing their appeal in terms of sustainability and cost-effectiveness

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• ], spirulina [16], Ti(OiPr)4/t-BuOOH [17], VO(acac)2)/t-BuOOH [18], and enzymatic oxidation [19] etc., which may compromise the environmental benefits (Scheme 1a,b) and take longer reaction times. Alternatively, a new green pathway is necessary for the Achmatowicz reaction to be performed in a faster and safer

• et al. [22] have demonstrated a combined use of flow and batch processes involving an electrochemical flow cell for the oxidation of furfuryl alcohols and subsequently utilizing the crude electrolysis mixture for hydrolysis in a traditional batch process to get the rearranged Achmatowicz product. As

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• ]. In contrast, the protocol reported herein provides 94–98% yield when employing longer chain-containing aldehydes (1c–e). In addition to resorcinol, 2-methylresorcinol is commonly used in resorcin[n]arene synthesis as radical oxidation of the methyl unit in the ArCH3 fragments provides a benzyl

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• functionalization of amides with alkenes under photoredox conditions. Another viable approach for amide functionalization through photoredox catalysis involves the nucleophilic addition, in the presence of base, of an amide to a radical cation obtained by oxidation of an unfunctionalized alkene moiety (Figure 1A

• ) [23][24][25]. The nucleophilic attack of the nitrogen atom on the oxidized C=C double bond results in the formation of a radical intermediate after deprotonation. This radical intermediate can proceed through various pathways (e.g., HAT, oxidation) to yield the desired final product. In the

• functionalization of amides with alkenes under oxidative conditions, the oxidation potential of the alkene plays a pivotal role in the oxidation to a radical cation through photoredox catalysis [26]. Alkenes that are less functionalized possess a higher oxidation potential, necessitating the use of potent

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• ]. Iodoethane was also shown to be an effective reagent furnishing the product in up to 56% upon heating to 40 °C (Table 1, entries 11 and 12). It was envisaged that oxidation of iodoethane led to formation of oxidized forms of iodide by C–I-bond cleavage, therefore tetrabutylammonium iodide was utilized to see

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• detection of benzaldehyde which was considered to be formed by the NaClO-mediated oxidation of benzyl alcohol generated by hydrolysis. Changing the oxidizing reagent to crystalline NaClO·5H2O nicely solved the problem with the realization of 86% isolated yield of 2b by the utilization of this oxidant (2

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• is produced in situ from the imidoyl chloride 9 [21]. The one-pot oxidation and ring-closure reaction [22][23] to iodoloisoxazolium(III) salt 7OTf and the salt metathesis with sodium tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF24) were then realized with 85% and 72% yield, respectively

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• (Table 1, entry 6). In contrast, zinc was not effective as an anode material in the carboxylation, probably due to competitive electrochemical reduction of zinc ions generated by electrochemical oxidation of the zinc anode. The deposition of a black precipitate was observed visually at the cathode (Table

• competitively occurs at the cathode, and an excess amount of electricity should therefore be necessary to obtain acceptable results. At the anode, on the other hand, dissolution of magnesium ions by electrochemical oxidation of magnesium metal occurs, preventing electrochemical oxidation of the product and

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• the electrochemical properties of functionalized catechols allows one to suggest the mechanism of their electrooxidation, establish electron transfer centers, and predict antioxidant activity based on electrochemical data. To determine electron-transfer centers, the oxidation potentials of the

• observed in the range of 0.94–1.25 V. It refers to the oxidation of the catechol moiety to the corresponding o-benzoquinone, as previously shown for related compounds [36]. The second redox transition at 1.55–1.84 V characterizes the oxidation of the sulfide fragment (Scheme 2). To confirm the

• participation of the catechol group in the first redox transition, the microelectrolysis of 3 was carried out at a controlled potential of 1.35 V in MeCN (2 h, 0.8 F/mol). After electrolysis, a decrease in the current intensity of the first oxidation peak is observed on the CVs of this compound (conversion

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• 24, which supported the hypotheses regarding the selectivity-determining transition states arrangement. It is important to note, that boronic acids 14 are highly sensitive to oxidation by air and could only be purified in air-free conditions and stored in airtight containers. Additionally

• generated from Togni’s reagent (145) to a double bond of the δ-alkenylamine, followed by intramolecular hydrogen atom transfer and a single-electron oxidation of the intermediate alkyl radical to form an imine that is then reduced by hydrogen donor 147 catalysed by CPA (R)-VAPOL (148). The

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• reagent detects nitrite formed by the enzymatic oxidation of NO) [44][45]. As shown in Figure 3, compounds 1a–e containing an aryl substituent at position 6 exhibited low NO-donor ability (0.3–4.5%). In contrast, compounds 1f–h with an aliphatic fragment showed moderate activity, with the maximum value

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• sites where benzylic C–H bonds readily undergo metabolism driven by cytochrome P450 oxidases via single-electron oxidation [24]. This metabolic lability may be tempered by hydrogen replacement with deuterium, an almost perfect bio-isosteric replacement (C–H to C–D) which maintains 3D surface, shape and