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

• ]. Results and Discussion We hypothesized that [D1]-aldehydes could be converted to [D2]-benzylic isocyanides using [D2]-formic acid via Leuckart–Wallach reaction followed by dehydration. Surprisingly, the Leuckart–Wallach reaction gave [D3]-formamides which are scarce in the primary literature. The common

• method to prepare [D1]-formamides (D–C=O) is through a Leuckart–Wallach reaction with an amine and [D1]-methyl/ethyl formate or [D1]-dimethylformamide [19][20]. Stockmann and co-workers produced [D2]-formamides (N–D, D–C=O) via acid-catalyzed nitrile hydrolysis with HCl and D2O [21]. Thus, using the

• Leuckart–Wallach methodology developed herein, deuterated aldehydes can be converted into [D2]-isocyanides. The optimized conditions for this reaction are summarized below (Table 1). It is important to note that 1 equivalent of formamide and excess [D2]-formic acid (Table 1, entry 2) leads to increased

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• Brønsted acid, such as Tf2NH and TfOH, with Bu4NBF4 might be effective to promote the gem-difluorination of alkynes because of the in situ generation of HF equivalents (Figure 1, reaction 6, chemical method). In addition, the electrogenerated acid (EGA) [43][44][45][46][47][48][49][50][51][52] from a

• organic molecules. Herein, we wish to report that the combination of the excess amount of Brønsted acid and Bu4NBF4 or the use of an EGA in Bu4NBF4/CH2Cl2 can serve as suitable reagents for the gem-difluorination of alkynes. These procedures are practical, simple and environmentally friendly, because HF

• ) was reacted with the Brønsted acid (X equiv) and the fluorine source (Y equiv) in the solvent (4 mL) at temperature of T (°C) for Z hours. The chemical yield of the desired product, (5,5-difluorohexyl)benzene (2a), was evaluated for reaction optimization by using the 19F nuclear magnetic resonance

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• used to establish a reference CFPS synthesis under standard conditions containing 2% PEG-8000. A concentration of 1.77 mg/mL sfGFP was obtained after 4 hours. The calculated fractional yield of 114% based on the added amino acid concentration is higher than expected, which can be explained either by

• (UTP), tRNA, coenzyme A (CoA), nicotinamide adenine dinucleotide (NAD), cyclic adenosine monophosphate (cAMP), folinic acid, spermidine, 3-PGA, and PEG-8000 to obtain a master mix. The master mix was assembled with the plasmid encoding for sfGFP respectively thscGAS-sfGFP and nuclease-free water, which

• , 1.5 mM ATP and GTP, 0.9 mM CTP and UTP, 0.2 mg/mL tRNA, 0.26 mM CoA, 0.33 mM NAD, 0.75 mM cAMP, 0.068 mM folinic acid, 1 mM spermidine, 30 mM 3-PGA, 2% PEG-8000, and 1 nM plasmid DNA. Reactions were incubated for 4 h at 37 °C with no shaking. Resulting fluorescence intensities were measured from 2 µL

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• 5 was prepared from phthalimide (1, Scheme 1). Iodination followed by hydrolysis afforded 4,5-diiodophthalic acid (2) in 46.7% yield. Esterification with 1-hexanol yielded compound 3 in 56.8% yield and the subsequent Sonogashira coupling with trimethylsilylacetylene provided compound 4 in 80.0

• is straightforward and has broad applicability, extending to other azidated molecules and polymers. Experimental Materials All reagents are purchased from TCI, Aldrich, and Kanto Chemical Co. Inc., and used as received. 4,5-Diiodophthalic acid was prepared according to a literature method [20]. A

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• thioesters and β-keto amides is reported. In refluxing water, the hydrolysis reactions of α-oxo ketene N,S-acetals in the presence of 1.0 equiv of dodecylbenzenesulfonic acid effectively afforded β-keto thioesters in excellent yield, while β-keto amides were successfully obtained in excellent yield when the

• N,S-acetals; β-keto amide; β-keto thioester; dodecylbenzenesulfonic acid; hydrolysis; Introduction In the past decades, the application of easily available and stable α-oxo ketene N,S-acetals as significant synthons has received more and more attention in organic synthesis due to their unique

• water under different conditions (Table 1). We initially tested the reaction in the presence of dodecylbenzenesulfonic acid (DBSA) in boiling water and found that the amount of DBSA has a dramatic influence on this reaction. Using 1.0 equiv of DBSA, the reaction efficiently gave the desired S-ethyl 3

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• 2356151). No significant improvement in the yield was observed by varying the reaction conditions. Surprisingly, the reaction of 1,3-diketone 1a, morpholine and acetone without the use of molecular sieves and acid catalysis (conditions A) resulted in 81% yield of meta-substituted aniline 3ab. Applying the

• with aniline resulted in low conversion of 1b even at prolonged reaction times (up to 10 days). The addition of molecular sieves, excess aniline, or acid catalysts did not significantly affect the conversion (Scheme 3). 1,3-Diketones with benzothiazole (1c, σm/σp 0.338/0.390) and oxazole (1d, σm/σp

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• overviews exist on mycotoxins in general [1][2][3], on selected Alternaria toxins [4][5][6][7][8][9][10][11][12], and on dibenzo-α-pyrones [13][14][15][16][17][18][19]. The current review will comprehensively deal with all naturally occurring polyketides derived from β-resorcylic acid (2,4-dihydroxybenzoic

• acid), whose biosynthesis is presumably starting from alternariol. The lactone moieties of these compounds are usually six-membered rings, where variations during or after polyketide synthesis occasionally give rise to five- or seven-membered rings or even to open structures with a free resorcylic acid

• respect seems to be available for alternariol or even for its derivatives. Compounds not containing a fully intact resorcylic acid (e.g., dendrocoumarin (C) [29], urolithin A (D) [30], or polygonumoside B (E) [31]) or containing more than the two hydroxy groups of the resorcylic acid (e.g., unnamed

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• –80%) along with their preliminary photophysical (absorption, emission and time resolved fluorescence lifetime) properties. The condensation reaction for assembling the required DPMs were catalyzed with trifluoroacetic acid (TFA) at 0 °C to room temperature (rt), and the stable dipyrromethanes were

• functional materials for diverse uses [1][5][6][7]. Notably, to synthesize this vital heptacyclic star‐shaped π‐conjugated polyarene framework, only a single acid-mediated co-trimerization step is required from an inexpensive and commercially available starting material, namely 1-indanone [8]. It is to be

• pointed out, though for the first time truxene was reported in 1894 by Kipping [9], whereby 3‐phenylpropionic acid in situ cyclized under acidic conditions to indan‐1‐one which under the same conditions offered a mixture of both isomers, that is truxene as well as isotruxene. However, the practical

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• Biginelli synthesis of dihydropyrimidinones/thiones/selenones via acetic acid or solvent-free Yb(OTf)3-catalyzed tandem reaction of β-ketosulfone (dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide), an appropriate urea, and arylaldehyde has been developed. The reaction proceeds with high chemo- and

• ) are the key methodology to access valuable heterocycles for medicinal chemistry projects. The classical Biginelli reaction (1893) is an acid-catalyzed, three-component reaction between an aldehyde, β-ketoester, and urea that produces 3,4-dihydropyrimidin-2(1H)-ones, also known as DHPMs (Scheme 1A

• amides, coumarins, alicyclic ketones, β-ketophosphonates, α-nitroketones, curcumin, and barbituric acid derivatives [1][2][8][9]. We analyzed a number of Biginelli-type products and publications and concluded that Se-containing DHPMs among the rarest examples and, in addition to this, ketosulfones have

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• Amorphous (SBA-15) and small pore-sized Mobil Composition of Matter (MCM-41) were applied and compared as supports of an organocatalyst. These silicas were modified by incorporating an organosulfonic acid group (propylenesulfonic acid) through a post-synthesis grafting method. Their catalytic performance

• was studied and compared in the esterification of methanol or glycerol with oleic acid (1). It was observed that substrate conversion and product yield also depended on the particle morphology. Rope-type propylsulfonic SBA-15 mesoporous silica gel showed the highest catalytic activity in both studied

• , contributing to more sustainable and efficient catalytic processes. Esterification of oleic acid (1) with propylsulfonic acid (Pr-SO3H)-functionalised mesoporous silica catalyst 4. Using confinement of organocatalytic units for improving the enantioselectivity of silica-supported organocatalysts in the Michael

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• hindrance. However, several examples of isocyanide insertion reactions into B–H and B–B bonds are known. For example, isocyanides coordinate to diborane (B2H6) or trialkylboranes (BR'3) to form Lewis acid–base complexes (RNC→BH3 or RNC→BR'3), but these complexes are thermally labile, and hydrogen or alkyl

• Lewis acid–base complexes (t-BuNC→BH3) to generate the corresponding isocyanide–boryl radicals 17 (t-BuNC→BH2•), which can be observed by ESR (Scheme 10b) [47]. However, the synthetic application of this boryl radical has not been investigated. Among the cyclic diboron compounds, a series of five

• acid [58]. Rainier et al. reported the thiol-mediated 5-exo cyclization of o-alkynylaryl isocyanides, which successfully afforded dithiolated indoles 22 (Scheme 15) [59]. However, depending on the reaction conditions, quinoline derivatives were also produced as byproducts (vide infra). The photoinduced

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• ), skew (S), and half-chair (H) conformations (Figure 1). Among them, chair’ shapes typically have the lowest energy and are thus preferred, except few cases in which different conformations can exist in a dynamic equilibrium, as for the iduronic acid that can adopt three low-energy solution conformations

• -translational modifications, including glycosylation, in which a carbohydrate chain is directly attached to a specific amino acid to generate glycoproteins and proteoglycans [27]. Based on the amino acid involved in the link with the carbohydrates chain, it is possible to classify different types of

• GalNAc combined with uronic acid (glucuronic or iduronic acid) or galactose residues, forming chains which can also be partially sulfated. GAGs family includes heparan sulphate (HS), dermatan sulphate (DS), chondroitin sulphate (CS), keratan sulphate (KS), and hyaluronic acid (HA) [31]. The extraordinary

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• emulsions. The polystyrene particles were treated with sulfuric acid to form a surface layer of sulfonated polystyrene. These particles were then used to produce Pickering emulsions, which were transformed into large-pore structures when treated with an alcohol/water mixture [12]. Another method involves

• . Titration of CMC with hydrochloric acid, followed by treatment with a mixture of hexamethylene diisocyanide and formalin led to the formation of compact particles with an average diameter of 40–80 nm (Figure 3A). These particles were the main building blocks for the construction of cage-like structures

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -dicarbonyl compounds and their one-pot transformation pave the way for MCR syntheses of pyrazoles. 1,3-Dicarbonyl compounds can, for example, be generated in situ from enolates and carboxylic acid chlorides. They can be converted to the corresponding pyrazoles 1 in a consecutive multicomponent reaction with

• , 3,4,5-substituted pyrazoles 5 are formed (Scheme 2) [45]. The Lewis acid catalyst accelerates the reaction via participation in the formation of β-diketonate complexes. Other carbonyl compounds suitable for pyrazole synthesis are 2,4-diketoesters 13. These intermediates can be prepared from diethyl

• serves a dual role as a Lewis acid and an oxidizing agent. However, a significant limitation of the method is that it only tolerates aliphatic 1,3-dicarbonyl compounds, as the reaction with aromatic carbonyl compounds leads to very low yields. Improved yields for the latter can be achieved by isolating

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• . With comparison to the rate of Z–E isomerisation on addition of acid to the PS systems, we show that factors beyond the production of protons (H+) upon X-ray radiolysis of water may have an effect to produce the large, rapid structural changes observed using SAXS. To conclude, we create a set of

• effect, but also as the medium for structural rearrangements. Effect of acidification The effect of acidification on isomerisation was further investigated using UV–vis absorbance spectroscopy, where excess hydrobromic acid (HBr) was added to AzoTAB and AAPTAB samples (25 μM) that had been preirradiated

• with UV light into the Z-rich PSS. HBr was selected as the acid to eliminate any effects from the Br− counterion on the self-assembly behaviour [36]. AzoTAB (in the Z-rich PSS) showed a rapid response to acidification with near-complete reversal to the E isomer within 60 minutes (Figure 4a). In

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• undergo deprotonation delivering the oxadiazole 24a. Alternatively, from 23b (R2 ≠ H), nucleophilic addition of methanol to oxycarbenium 26b yielded the oxadiazoline 24b (Scheme 6) [41][42]. In 2020, Lei, Zhang and Gao et al. described the electrooxidative cyclization of in situ-generated α-keto acid

• reaction initiated with anodic formation of iodine. The latter would react with hydrazone 83 to form the zwitterionic species 86 under basic conditions. Subsequent formal (3 + 2)-cycloaddition with the quinoline 84 formed fused system 87 which underwent elimination of iodide and sulfinic acid to furnish

• generate the α-iodo ketone-derived NH-tosylhydrazone 92 and ultimately the azadiene 93 upon elimination of HI. In agreement with a previous report [63], further formal (4 + 1) cycloaddition with S8 followed by elimination of S7 and sulfinic acid gave rise to the aromatic cycle 91 (Scheme 17) [64]. The

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• : Allostreptomyces; β-alkylpyrrole; conformer; cytotoxic; DFT; 4-formylpyrrole-2-carboxylic acid; Introduction β-Alkylpyrroles are key structural motifs in biomolecules and functional organic materials [1]. For instance, β-alkylpyrroles are the main building blocks for the life-essential tetrapyrrole pigments

• (porphyrins) including heme, chlorophyll, and vitamin B12 [1][2] (Figure S54 in Supporting Information File 1). Porphobilinogen, the fundamental biological precursor of tetrapyrroles, is biosynthesized via asymmetric condensation of two δ-aminolevulinic acid molecules [2][3]. From another aspect

• many marine natural products [6][7], pyrroles substituted with long hydrocarbon chains (pyrrole lipids) are seldomly isolated, and their presence is limited to certain marine organisms [8]. A series of 3-alkylpyrrole-2-carbaldehydes/carboxylic acid/methylcarboxylate was reported from the marine sponge

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• generated in the flow reaction system through the intramolecular cyclization of ortho-carbonyl alkynylbenzene derivatives by the π-Lewis acidic metal catalyst AgNTf2 and the subsequent proto-demetalation with trifluoroacetic acid. The 2-benzopyrylium intermediates underwent further photoreactions with

• intramolecular cyclization followed by proto-demetalation with trifluoroacetic acid (TFA). In catalytic cycle II, photoexcitation of the generated 2-benzopyrylium intermediates A under light irradiation facilitates single-electron transfer (SET) from benzyltrimethylsilane derivatives 2 as the donor molecule

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• the chelation pathway proposed in Figure 5, we hypothesized that 18 (Figure 9) would provide a model for exploring the mechanism further. If chelation between an electron-rich oxygen atom from a substituent and a Lewis acid (such as Cs+ or P+) were taking place, we would expect regioselectivity for

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• applicable to a broad range of substrates, however, it utilizes a catalyst that is not commercially available and small heteroaromatic rings are underrepresented in the scope. Recognizing the importance of small heteroaromatic rings and the amino acid motif in medicinal chemistry [30][31][32][33], and aiming

• subsequent re-esterification was necessary to achieve the desired ketoester. Reduction of the oximes Oximes are commonly reduced to the corresponding amines using either palladium on activated carbon and hydrogen gas [65][66][67][68], or with zinc and a Brønsted acid as source of hydrogen [68][69]. Both

• first attached to carboxylic acid functionalized DNA headpiece 7a (first reverse amidation). Next, the ester was hydrolyzed to obtain acid 9, and finally, a second reverse amidation with aniline afforded 10. Both the reverse amidation and the ester hydrolysis were performed following literature

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• peracetic acid as a terminal oxidant [20]. Recently, Kočovský et al. disclosed a method employing 2-methylbenzamide and benzonitrile to yield 3-aryl-substituted isoquinolinone derivatives in the presence of n-butyllithium [21]. On the other hand, the intramolecular oxidative cyclization is also a viable

• migration and reductive elimination, along with the release of iodobenzene and sulfamic acid. Cyclization of protonated G takes place to afford the intermediate H. Finally, release of water and β-proton elimination produces the rearranged product 3a (Scheme 8). Conclusion In summary, we reported the

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• intermediate (i.e., the diarylamines’ radical cation) and indicates the dominance of the intramolecular cyclization over the intermolecular C–N coupling process. Oxidation of diarylamines in the presence of an excess of trifluoroacetic acid gave no targeted pyridoindazolium salts, whereas the amount of

• . Our experiments with the acid additives (see above) showed that protonation of the pyridyl group suppresses the pyridoindazolium salt formation. Voltammetry testing also showed that 2,6-lutidine addition facilitates oxidation of the amine (Figure 2); the peak potential was of 100 mV shifted toward

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• due to the increased conductivity of the electrolyte solution (Table 1, entry 1). The reaction did not take place without electricity and most of the starting material was recovered (Table 1, entry 3). The addition of trifluoroacetic acid (TFA) was advantageous in terms of the reproducibility, which

• was in good accordance with the observation reported by Yoon (Table 1, entry 4). The use of acetic acid (AcOH) instead of TFA gave a slightly lower yield of the five-membered pyrrolidine 2 (Table 1, entry 5). Although a constant-potential condition at 1.8 V was also productive, the constant-current

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• 191036, Russian Federation 10.3762/bjoc.20.164 Abstract In this work, we report an efficient approach to 2-oxoazetidine-3-carboxylic acid derivatives based on a thermally promoted Wolff rearrangement of diazotetramic acids in the presence of nucleophiles. The method allows easy variation of the

• well as a wide range of nucleophiles provides access to a structural diversity of medically relevant 2-oxoazetidine-3-carboxylic acid amides and esters. Keywords: β-lactams; diazotetramic acids; nucleophiles; spirocycles; thermolysis; Wolff rearrangement; Introduction The importance of the β-lactam

• ketenes 2 generated by a thermally promoted Wolff rearrangement [3]. The interaction of such ketenes with nucleophiles of different nature could serve as a source of libraries of structurally diverse 2-oxoazetidine-3-carboxylic acid derivatives 3 (Scheme 1). The 2-oxoazetidine-3-carboxylic acid

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• improvement through inverse agonism at histamine receptor 3 (H3) using recombinant isoforms. This finding corrects their previous assumption of betahistidine acting as an antagonist. Inhibition of cAMP formation and [3H]arachidonic acid release concluded the inverse agonist role. Five-membered heteroaromatic

• -heteroarylethylamine chemical space is constituted by the biogenic amine histamine (43). In a similar fashion as dopamine and epinephrine produced from ʟ-phenylalanine along the catecholamine pathway, histamine is generated from the amino acid ʟ-histidine (42) via enzymatic decarboxylation promoted by ʟ-histidine

• decarboxylase (Scheme 8) [45][46][47]. Histamine is commonly degradated by two enzymes: diamine oxidase (DAO) to produce (imidazol-4-yl)acetic acid (44), or histamine N-methyltransferase (HMT) to N-methylhistamine 45. Monoamine oxidase B (MAO-B) transforms N-methylhistamine into (N-methylimidazol-4-yl)acetic