One-pot four-component sequential synthesis of S-alkyl dithiocarbamates using lipase as a biocatalyst

• Mansour Shahedi,
• Pargol Tahmasebi pour and
• Zohreh Habibi

Beilstein J. Org. Chem. 2026, 22, 1048–1056, doi:10.3762/bjoc.22.83

• (CS2), and amines. Initially, α,β-unsaturated carbonyl compounds, serving as Michael acceptors, were generated from aldehydes and ethyl acetoacetate through a decarboxylative Knoevenagel reaction under mild conditions, using lipase as a biocatalyst. These intermediates then sequentially undergo a

• reaction efficiency when compared to the optimized method (Scheme 5b). Based on the control reactions and previous studies a mechanism is proposed (Scheme 6). The reaction begins with a nucleophilic attack by the activated ketoester, facilitated by the triad amino acids of lipase, on the carbonyl group of

Synthesis of novel 1,2,4-oxadiazole-isoxazoline hybrids and their in silico potential with adenosine receptors

• Pshtiwan S. Mohammed,
• Mohammed K. S. Dalo,
• Onur C. Yazıcı,
• Muhammet Yildirim and
• Akın Sağırlı

Beilstein J. Org. Chem. 2026, 22, 1033–1047, doi:10.3762/bjoc.22.82

• , such as sulfisoxazole, oxacillin, and acivicin, have been clinically utilized for many years [21][22][23][24][25][26][27][28] (Figure 1). The synthesis of 1,2,4-oxadiazole derivatives can be achieved through various efficient methods, such as the cyclocondensation of amidoximes with carbonyl compounds

Semisynthesis, characterisation, and antibacterial evaluation of a novel lecanoric acid-derived amide library

• Ethan D. Abbott,
• Sasha Hayes,
• Jonathan M. White,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 1023–1032, doi:10.3762/bjoc.22.81

• ester carbonyl by the primary amine (i.e., isopentylamine) taking place, thus forming the desired amide analogue 6 along with orsellinic acid (4). The 1 h reaction was shown to produce the highest yield (i.e., 13%), generating 2.7 mg of the amide product 6 (Scheme 1) in high purity (>95%) following C18

• methylene groups (δC 38.1, 37.1), one aliphatic methine carbon (δC 25.2), and one carbonyl carbon (δC 167.7). The presence of phenols in 6 was supported by a bathochromic shift of the UV spectrum upon addition of base (NaOH) [25][26]. One spin system was identified from the COSY spectrum, which was the

Rh(III)-catalyzed chelation-assisted C–H activation/annulation of 2-arylimidazolines with cyclic diazo-1,3-dicarbonyl compounds: a novel approach to tetracyclic annulated derivatives of 2,3-dihydroimidazo[2,1-a]isoquinoline

• Ivan Lyutin,
• Grigory Kantin,
• Olga Bakulina and
• Dmitry Dar'in

Beilstein J. Org. Chem. 2026, 22, 997–1003, doi:10.3762/bjoc.22.78

• methylene group of the dimedone moiety at 4.18 ppm with both protons from the methylene group of the imidazoline moiety at 2.55 and 3.60 ppm was observed for the major isomer 4g. Next, the scope of suitable diazo carbonyl compounds was examined. In addition to dimedone, 1,3-cyclohexanedione and its 5-phenyl

• protodemetallation that delivers CAr-alkylated intermediate F and regenerates the active catalytic species. The target tetraheterocyclic product 4 is formed after intramolecular condensation between the carbonyl group and the imidazoline nitrogen of intermediate F. To support this mechanism experimentally, we have

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• spectrum of the nitroxide 9a (TEEPONE) was identical to that reported in the literature [21], and the IR spectrum of 9d was similar, with a strong absorption band at 1716 cm−1, characteristic of the carbonyl (C=O) stretching vibrations. The 1H NMR spectra of the reduced derivatives of 9a,d showed no

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• ]. Hydroamination simultaneously forms C–N and C–H bonds from simple and readily available starting materials without prefunctionalization. When applied to electron-deficient alkenes such as α,β-unsaturated carbonyl compounds, nitroalkenes, or vinyl sulfones, this transformation is often categorized as an aza

• -Michael addition [13][14][15][16][17][18]. In such cases, the reaction provides direct access to β-amino carbonyl derivatives and related motifs that serve as versatile intermediates in synthetic and medicinal chemistry. Despite its conceptual simplicity, catalytic hydroamination remains challenging. This

• selective hydroamination chemistry. Review Copper-catalyzed aza-Michael addition Early studies on copper–amido complexes by Gunnoe The aza-Michael addition of (hetero)aromatic amines to electron-deficient olefins provides a straightforward and atom-economical route to β-amino carbonyl, β-amino sulfone, and

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• carboxylation strategy using CO2 as an inexpensive, readily available, and non-toxic C1 source. In principle, CO2 can serve as a carbonyl source through nucleophilic addition followed by protonation to furnish the corresponding carboxylic acid. On the basis of this design (Figure 2a), brominated SiR precursors

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• . Considering that the condensation of acyldiazomethanes to aldehydes leads to the β-hydroxy-α-diazo carbonyl compound [20][21][22], we hypothesized that such condensation of aldehydes with 2-(diazoacetyl)-2H-azirines could yield the corresponding azirinyl-substituted diazo compounds. This paper describes the

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• reagent, 1) was used to label the α-amino group of insulin during sequence determination (Scheme 1a). Its selectivity over lysine’s ε-amine originates from the low pKa of the N-terminus, influenced by the adjacent carbonyl group and systematically characterized at ≈6–7 (Scheme 1b) [7]. Building on this

• sodium periodate (Scheme 2a) [13], selective modification of glutamate using Rapoport’s salt (4) which has generated modified trastuzumab in moderate yield (67%; Scheme 2b) [14], or pyridoxal phosphate (PLP, 5)-mediated carbonyl formation at residues such as serine, threonine, glycine, alanine, or

• modifications remains limited. The following examples illustrate recent advances in recruiting enzymes for native-sequence labelling, all of which rely on reaction mechanisms that activate carbonyl groups (Scheme 13). One of the most studied protein-modifying enzymes is sortase A. Recognising the LPXTG motif

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• carbonyl group with a γ-lactam system, which enables participation in a wide range of nucleophilic additions, condensations, and cyclizations [7]. As a result, isatin has proven to be a particularly powerful synthon for the construction of 2-oxindole derivatives, including a large variety of spiro-fused

• aromatic pattern of the isatin core. The IR spectrum showed a strong imine C=N band at 1610 cm−1, and the absence of the C-3 carbonyl stretching band confirmed complete condensation. The 13C NMR spectrum revealed multiple sets of closely related signals, consistent with the presence of three C=N

• retained the four-signal pattern of isatin (H4', H5', H6', H7'), slightly shifted by the new structural environment. In the 13C NMR spectrum, the amide carbonyl appeared at δ 176.5 ppm, while a key quaternary carbon at δ 61.0 ppm (C3‘) – formerly the C-3 isatin carbonyl carbon – confirmed the formation of

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• corresponding ketones complicating the synthetic protocol. Therefore, the Knoevenagel condensation seemed to be an alternative and preferable approach. Previously reported syntheses of diazafluorenylidenes employed diazafluorenones as the carbonyl component which are reacted with an active methylene moiety like

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• systems or the phenyl ring at the 3-position of the isoxazole to enhance hydrophilicity and improve pharmacokinetic properties [42]. Co-crystallization of GS-4997 with ASK1 unveiled key stabilizing interactions in the active site. Specifically, the amide carbonyl forms a hydrogen bond with the backbone

• moieties of Z8 formed hydrogen bonds with the key residues ARG-331 and HIS-447, respectively. Similarly, in the ASK1 binding pocket, the isoxazole, carbonyl, and triazole groups of Z8 engaged in hydrogen bonding with residues GLY-759, VAL-757, and LYS-709, respectively. Notably, the binding sites of Z8

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• -carbonyl or 3β-hydroxy function in this ring. Additionally, the accumulation of the dephosphorylated form of the BES1 protein, which is part of the BRs signaling pathway and control their activity, has been evaluated as well. The results are analyzed in terms of BR analog’s structure and compared with

• electronegative effects on the aromatic ring enhance the analogs’ bioactivity in the RLIT. A comparison of results obtained for compounds with the same substituent at C-22, but having just one hydroxy group at C-3 (3) (TE analogs) [28], or only a carbonyl group in this position (3a) (3-DT analogs) [31] is given

• in Table 2. The data indicate that derivatives with a OH group at C-3 (TE analogs) are much more active than derivatives with a carbonyl group in this position (3-DT analogs). However, the addition of another OH group at C-2 (CAT analogs) increases the activity of analogs substituted with p-methyl

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• high concentration of ≈80% acetic acid (pH ≈3), it seemed plausible that activation of the dienone carbonyl group would occur by hydrogen-bonding, rather than complete proton transfer to the carbonyl oxygen lone pairs [29]. We therefore included explicit solvation with acetic acid in our computational

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• derivatives with multiple chiral centers under high regio- and stereocontrol. Currently, strategies using azomethine ylides based on imino esters or α-amino acids with a variety of cyclic and acyclic carbonyl compounds dominate. Enantioselective (3 + 2) cycloaddition reactions of azomethine ylides obtained

• , cyclic and acyclic unsaturated substrates, and fullerenes are useful dipolarophiles. This reaction method allows for the single-step creation of a wide variety of complex polyheterocyclic systems that may be useful for practical applications. Keywords: alkenes; α-amino acids; azomethine ylides; carbonyl

• acid or its ester (Scheme 1). In both cases, condensation of amino acids with carbonyl compounds occurs; however, in the first case, decarboxylation occurs with the in situ formation of azomethine ylides, which subsequently undergo cycloaddition to unsaturated substrates. The advantage of the first

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• efficient macrocyclization methods, including tetracarbonylnickel-promoted cyclization of allylic dibromide [17][18], copper-mediated intramolecular carbene–olefin cyclization [19], titanium-induced intramolecular carbonyl coupling [20], and organozinc carbenoid-mediated intramolecular cyclopropanation [21

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• acceptors (carbonyl groups). Trifluoromethylation of anisole afforded product 11 in 57% yield, with the ortho-isomer identified as the major product. Compared with anisole, thioanisole, a less electron-rich substrate, produced a mixture of ortho-, meta-, and para-isomers 12 in a combined yield of 33%, with

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• , National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan Department of Chemistry, School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan 10.3762/bjoc.22.43 Abstract The reduction of carbonyl compounds

• : bimetallic nanostructure; carbonyl reduction; continuous-flow reaction; heterogeneous catalyst; subatmospheric hydrogen; Introduction The reduction of carbonyl compounds, ketones and aldehydes to alcohols is a fundamental and important reaction in organic synthesis that can provide valuable chemicals such

• often suffers from insufficient reactivity and conversion, even under harsh reaction conditions, such as high temperature and pressurized hydrogen, or when employing advanced technologies [8][9][11][12]. The selective hydrogenation of carbonyl moieties often needs to overcome the problem of

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• in Figure 2) likely inhibits the effective interaction of the substrate with the chiral catalyst, resulting in highly enantioselective kinetic resolution. Cymantrene is far less electron-poor than ferrocene due to the presence of the three carbonyl ligands, which are strong π-acids, on the manganese

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• epoxide 9b, the more positively charged epoxide carbon is sterically shielded by the neighbouring ester carbonyl group. As a result, nucleophilic attack occurs at the sterically more accessible, albeit less positively charged, epoxide carbon. These observations indicate that the regioselectivity of

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• colorless and amorphous substance. The molecular formula was determined as C18H22O5 by high resolution electrospray ionization mass spectrometry (HRESIMS), thus containing one more oxygen atom than the melifoliones. The UV spectrum showed a maximum at 250 nm, typical for an α,β-unsaturated carbonyl

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• protected with TESCl, then regioselective oxidation of the primary TES ether and addition of vinyl grignard led to 87. Another oxidation afforded α,β-unsaturated carbonyl 88 and acidic treatment with BnOH triggered the oxa-Michael reaction and transketalization towards tetracyclic 90. Following Kishi

• and the so obtained α,β-unsaturated carbonyl was reattacked by the adjacent hydroxy moiety via oxy-Michael reaction to form 102. This sequence is shown in detail in Scheme 10 below. From here, a sequence involving the oxidation of the unprotected 1,2-diol moiety towards an intermediate aldehyde, Ni(II

• α,β-unsaturated carbonyl was reattacked by the alcohol (oxy-Michael reaction, see reaction sequence in Scheme 10) leading to a diastereomeric mixture of 323 (4:1 dr). 323 was deprotected, oxidized and methylenated to afford 324 in 28% yield. Overall, 324 was obtained in a total yield of 3% over a

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• and have found diverse applications across both biomedical and industrial fields [25][26]. Hydroxamic acids are also well known for their strong chelating ability toward uranyl, forming stable complexes through the synergistic coordination of the carbonyl and hydroxylamine groups [27]. Uranium is a

• donor atoms, a carbonyl oxygen and a hydroxy oxygen, that can simultaneously coordinate to a uranyl ion [77]. In supramolecular systems, not all hydroxamic acid groups necessarily bind uranyl ions, as steric hindrance and site accessibility can limit coordination to a subset of available sites [78]. A

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall

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

• another, with a Se···Se distance of 3.703 Å. The second is a selenium–carbon (Se···C) interaction as shown in Figure 2c, where the molecules are arranged in a top-down orientation [54]. In this orientation, the Se motif of one molecule interacts with the carbonyl carbon of another molecule, showing the Se

• . Similarly, for compound 8, the charges were −0.588 (N), −0.539 (O1), −0.506 (O2), and −0.506 (O3) as shown in Figure 5b. The selenium atom displayed Mulliken charge values of −0.045 and −0.039 for compounds 7 and 8, respectively. The carbonyl carbon of the naptthalimide ring features relatively positive

• showing stronger binding, attributed to its additional π–sulfur interaction with Met742. The hydrogen-bonding interaction observed between the naphthalimide carbonyl oxygen and the Met-742 hydrogen atom correlates well with the negative Mulliken charge (vide supra), suggesting that the negatively charged