Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• . Glutaminases catalyze the hydrolysis of glutamine to glutamate, which supports the biosynthesis of amino acids, lipids, and glutathione and can also be oxidatively deaminated to α-ketoglutarate and enter the citric acid cycle. The “glutamine addiction” of cancer cells has made glutaminase an attractive

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• regions indicate more electronegative areas. For both compounds 7 and 8, the oxygen atoms exhibit the highest electronegativity, indicating potential nucleophilicity and the ability to readily participate in hydrogen bonding with amino acids through non-covalent interactions. Overall, MEP mapping reveals

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• lone electron pair at the nitrogen atoms and protonated amino acids of proteins. However, oxazolo[5,4-d]pyrimidine forms more stable complexes, which is in good agreement with in vitro studies [10]. We have already shown the anticancer potential of 7-N-derivatives of 2,5-diaryl[1,3]oxazolo[4,5-d

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• azabicyclo[3.1.0]hexane and cyclopropa[a]pyrrolizine moieties can be synthesized via 1,3-dipolar cycloaddition between cyclopropene derivatives and azomethine ylides generated in situ from alloxan and α-amino acids [43]. In [43], a mechanism was proposed for the formation of azomethine ylides from alloxan

• and α-amino acids, which includes a stage of decarboxylation of the intermediate lactone. It is worth noting that generating azomethine ylides via decarboxylation of α-amino acid derivatives is a common practice in synthetic chemistry [44][45][46]. It was shown in our recent works that spirocyclopropa

• alloxan and α-amino acids) reacted with N-methylmaleimide was published by Ronald Grigg’s group in 1994 (Scheme 3) [52]. The authors reported the synthesis of spirobarbiturates containing various substituents: R’ = iPr (67%), Bn (61%), and Ph (66%). In this work, which is a continuation of studies on the

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• . This is consistent with the relative strength of hydrogen bonds (5–40 kcal mol−1) compared with typical hyperconjugative interactions [20]. Finally, because neutral amino acids dominate in the gas phase whereas zwitterions prevail in solution [21][22][23][24], the zwitterionic form of DFMO was examined

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• carboxylic acids [4]. The trichloromethyl group is a convenient precursor of the carboxylic function, which determines their use in the synthesis of α-amino acids [5]. A number of natural trichloromethyl-containing compounds are metabolites of symbionts of marine sponges – cyanobacteria [6][7][8] – and have

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• ). The developed dimerization protocol proved scalable to 100 g scale, affording 40 g of the desired dimer 61b in 47% yield. Subsequent removal of the two Boc groups with TMSI, followed by HATU-mediated amide coupling with various amino acids 65–67, furnished the diketopiperazine precursors 68–70

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• alkaloids belong to the class of steroid alkaloids and are pseudoalkaloids, as they emerge biogenetically from steroidal biosynthesis via cholesterol and not, as usual for alkaloids, from amino acids [1]. For synthetic chemists, this combines challenges for steroid and alkaloid total synthesis and poses

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