The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• consisting of a combination of isoxazolidine rings [36][37][38][39][40][41]. It has been demonstrated that such cycloaddition reactions are also employed in the efficient preparation of biologically active molecules, including nucleosides, β-lactam class antibiotics, peptides, and amino acids, as well as

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• cross-electrophile coupling of alkyl halides and nitroalkanes [76]. Yang and co-workers reported photoenzymatic asymmetric C(sp3)–C(sp3) oxidative cross-couplings between organoboron reagents and amino acids (Scheme 9) [37]. The authors used a synergistic system consisting of an engineered threonine

• aldolase, a photoredox catalyst, and an oxidizing agent. With this catalytic system, they were able to accomplish the C–H functionalization of glycine and α-branched amino acids, obtaining α-tri- and tetrasubstituted amino acids with moderate to good yields, good diastereoselectivity, and high

• )–C(sp3) coupling reactions between organoboron compounds and amino acids. Electrochemical α-alkenylation reactions of 2-acylimidazoles catalyzed by a chiral-at-rhodium Lewis acid. Regio- and enantioselective electrochemical reactions of silyl polyenolates catalyzed by a chiral nickel catalyst.

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• of the Targets Our study started by a detailed analysis of the sequence of amino acids in CLK3 compared to the three other CLKs. There are several differences but one appeared very significant (Figure 1A): CLK3 has a polar lysine in position 241 while the other CLKs have a nonpolar leucine. Further

• present in DYRK kinases. Nevertheless, by highlighting the role of the lysine 241, the present work paves the way towards the long-term goal of getting more potent and selective inhibitors of this understudied CLK3 kinase. A) Sequence of amino acids in CLK3 as compared to the three other CLKs; B

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• amino acids [8][9][10]. Sets of reactive probes are generally prepared using robust reactions, most usually amide formation, chosen from the toolkit that currently dominates medicinal chemistry [11] which may, in turn, limit probe structural diversity. We have developed a unified connective approach for

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• pharmaceutical and agrochemical industries [38][39]. Various types of catalysts are used to enhance the efficiency and selectivity of the Knoevenagel reaction, including Lewis acids, ureas/ thioureas, amino acids, and bases such as alkali metal hydroxides, alkali metal alkoxide, amines, etc. [37][40][41][42][43

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• mechanisms that will be detailed in this article, researchers have made progress in the transport of amino acids and molecular peptides across membranes using macrocycles in recent years [35][36][37]. These works have paved the way for the potential application of remote-controlled membrane transport

• drug design and therapeutic strategies. Notably, PA derivatives also exhibit specificity in recognizing important molecules in biological processes, such as acetylcholine [80], amino acids [81], doxorubicin (DOX) [82] and antibiotics [83], etc. Among the many derivatives, water-soluble pillar[5]arene

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• human system. In this study, we isolated two previously undescribed N-salicyl-amino acids as natural products (1 and 2) and other two new derivatives (3 and 4) from the organic extract of a culture broth in a modified starch–glucose–glycerol (SGG) medium of Pseudomonas sp. UIAU-6B. The structure of the

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• co-workers reported an unprecedented synthesis of 3-aryl-3-aminooxetanes 156 from amino acids 155 utilising a combination of photoredox and nickel cross-coupling catalysis (Scheme 39) [90]. The reaction uses low catalyst loadings, gives moderate to excellent yields and tolerates various functional

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• accordance with coupling constants and resulting dihedral angles. Keywords: conformational restraints; dihedral angle NMR; half-chair conformation; modified amino acids; pipecolic acid; stereoselective hydrogenation; Suzuki–Miyaura cross-coupling; Introduction Non-proteinogenic amino acids play an

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

• pharmacokinetics [15][16], stability against degradation [17] and general stability [10][18] of the peptide [19]. One of those amino acids is pipecolic acid [20][21], a homolog of proline with a six-membered piperidine ring. Pipecolic acid has similar features as proline in regard to its rigid nature and turn

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• projecting outward denoted by an asterisk. Furthermore, the resulting crystal structure reveals that 1 is also a distorted planar macrocyclic system consisting of the amino acids carbonyl oxygens facing inside the ring. All three benzyl groups are located above a single plane (more figures are provided in

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• Maurizio Iannuzzi Thomas Hohmann Michael Dyrks Kilian Haoues Katarzyna Salamon-Krokosz Beate Koksch Institute of Chemistry and Biochemistry, Freie Universität Berlin, Arnimallee 20, 14195 Berlin, Germany 10.3762/bjoc.21.52 Abstract Fluorinated amino acids are essential building blocks in the

• spheres of protein engineering and medicinal chemistry. In the last decades, a large number of different synthetic strategies have been developed to produce a large variety of fluorinated amino acids. Still, obtaining fluorinated amino acids in great quantities can be challenging, or the corresponding

• pathways are heavily time-consuming and synthetically challenging. In this context, chiral Ni(II) complexes can be powerful tools to obtain tailor‑made non‑canonical amino acids. In this work, we wanted to take advantage of this strategy and extend the range of this method to include additional fluorinated

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• under constant current conditions in aqueous acetonitrile and provides access to N-sulfonyl, N-benzoyl, and N-Boc-protected 2-aminoproline derivatives. Keywords: anodic oxidation; decarboxylation; electrosynthesis; Hofer–Moest reaction; non-proteinogenic amino acids; Introduction Non-proteinogenic

• cyclic amino acids are common structural motifs in the design of small-molecule drugs and peptidomimetics [1]. For example, the clinically used anesthetics carfentanil (1) and remifentanil (2), the FDA-approved antipruritic medication defelikefalin (3), and the arginase inhibitor 4 [2] possess cyclic α,α

• -disubstituted piperidine-containing amino acid subunits. Likewise, a cyano-substituted cyclic aminal is a core structural unit of the fibroblast activation protein inhibitor 5 [3] (Figure 1). The widespread use of non-proteinogenic cyclic amino acids in drug discovery justifies both the design of new analogs

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• native amino acids, by enzymatic coupling, or by bioengineering for the incorporation of non-canonical amino acids [18][19]. In fact, incorporating non-natural amino acids significantly broadens the scope of reactions that can be used in bioconjugation. As an example, click chemistry comprises one

• particularly useful and important tool in which azides and other dipolar species engage with reactive alkenes and alkynes on non-canonical amino acids [20]. Transition-metal-mediated processes, including metathesis reactions, aryl cross-coupling reactions, and conjugate addition reactions with dehydroalanine

• derivatives round out the most predominant reactions used on non-natural amino acids. However, even though bioengineering allows the incorporation of non-canonical amino acids with astounding effectiveness and near-complete selectivity, this technology is exceedingly expensive and time-consuming, and the

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• this study, we present an innovative, sustainable approach to synthesizing hydantoins (H2a–j) directly from amino acids. This method employs a column chromatography-free, two-step, one-pot microwave-assisted synthesis that delivers hydantoins in yields ranging from 34% to 89%. The protocol demonstrates

• accessibility of these bioactive compounds for pharmaceutical applications. Keywords: amino acids; hydantoin; microwave-assisted; one-pot reaction; Urech synthesis; Introduction The hydantoin moiety is a scaffold found in many biologically active compounds exhibiting a diverse range of properties, including

• antibacterial [1], antiviral [2], anticancer [3], anti-inflammatory [4], and anticonvulsant [5]. Hydantoins were traditionally accessed from amino acids by conversion to urea derivatives followed by cyclization (Urech reaction) or from carbonyl compounds through the cyanohydrin intermediate (Bucherer–Bergs) [6

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• ) 46 (Scheme 41) [97]. Unfortunately, this procedure does not work properly when amino acids or ammonia are used as amine components. In the case of ammonia, the corresponding imine was not generated, but rather a byproduct that incorporated two molecules of isocyanide 47 (Scheme 42). It was suggested

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• , Chiba 263-8522, Japan 10.3762/bjoc.21.43 Abstract β-Amino cyanoesters are important scaffolds because they can be transformed into useful chiral amines, amino acids, and amino alcohols. Halogen bonding, which can be formed between halogen atoms and electron-rich chemical species, is attractive because

• excellent enantioselectivities (Figure 1c). Despite these successful examples, the construction of only one stereocenter has been reported to date. The Mannich reaction has great importance because of its utility in the preparation of useful chiral molecules such as amines [36], amino acids [37], and amino

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• binding of tryptophan is therefore important for diagnostic and medicinal applications. Recently, we reported a glucose naphtho crown ether which is a chemoselective receptor for the esters of aromatic amino acids, in particular tryptophan, in water. Herein, we demonstrate that the same compound also

• binds free tryptophan selectively in aqueous media. Furthermore, it is capable of binding to tryptophan within model tripeptides. The naphthalene functionality in the glucose-derived receptor enables the study of guest binding using fluorescence spectroscopy. Keywords: amino acids; macrocyclic

• for the binding of free, unprotected tryptophan. To determine, if 1 binds tryptophan selectively over other amino acids we also studied phenylalanine, glutamic acid, lysine, and leucine as guests. We chose these amino acids to verify, how the character of their side chains (Phe – aromatic, Glu

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• functionalities of naturally occurring amino acids, synthetic polypeptides offer a robust platform for designing drug delivery systems that meet the criteria of biodegradability and biocompatibility [13]. The present study focuses on a polysarcosine and poly-ʟ-(benzyl glutamate) block copolymer (PSar-PBLG), as it

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available

• ]. Amid the growing popularity of biomolecular drug candidates, the late-stage modification of peptide scaffolds has gained significant importance [28]. A particularly interesting class of amino acids for late-stage diversification consists of dehydroamino acids (Dha). Dha derivatives have shown

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• synthesis of tripeptides incorporating new fluorinated heterocyclic hydrazino acids, based on the tetrahydropyridazine scaffold is described. Starting from simple fluorinated hydrazones, these non-proteinogenic cyclic β-amino acids were easily prepared by a zinc-catalyzed aza-Barbier reaction followed by an

• ; Introduction The synthesis of molecules capable of mimicking the various secondary structures and key functions of proteins is a major challenge in medicinal chemistry, especially in the fields of protein–protein interactions [1][2]. Accordingly, the incorporation of heterocyclic amino acids into peptides

• is known about its β-analog (Figure 3), although β-amino acids have been shown to strongly modulate the structural, metabolic, and biological characteristics of peptides [13]. Finally, it is well known that fluorine is a very useful tool in medicinal chemistry as the incorporation of fluorinated

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• substituted 1,4-benzodiazepin-3-ones using the UDC method. This process involves N-Fmoc-amino acids, isocyanides, amines, and derivatives of 2-fluorobenzaldehyde (Scheme 15). Ugi-4CR/reduction/cyclization (URC) strategy: The URC pathway enables the synthesis of benzodiazepines by using amine surrogates, such

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

• recognizes and activates a specific substrate BB. Notably, the BBs are in most cases amino acids, wherein a much broader variety are used in NRP biosynthesis than the 20 canonical amino acids used in protein biosynthesis [52]. The modules are usually arranged co-linearly to the BGC sequence, which makes

• underexplored by two-fold a particular BB (or a group of BBs with similar chemical structures), respectively (Figure 3c). Phenylglycine and its derivatives (the sp2 group of BBs, Figure 3d) turned out to be the most oversampled group of BBs. This group of BBs included noncanonical amino acids characteristic of

• , respectively. Based on the position of the nucleophile, a NRP can be cyclized head-to-tail, via an amino acid side-chain, a nucleophilic heteroatom on the N-terminal fatty acyl chain, or as a multimer of repeating sub-structures (Figure 5b). The ring size, ratio of ʟ- and ᴅ-amino acids, etc. may also be the

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• acceptors [13][14][15][16][17]. The Michael addition with fluorinated acceptors finds application in the synthesis of, among others, fluorinated amino acids, which can be a structural motif in many biologically active compounds [18]. There are also known studies on the incorporation of highly reactive