Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• ], tetrahydrobenzo[b]pyrans [68], and pyrrolo[3,4-c]quinolinediones [69]. EDDA favors the enol formation of the thiazolidinone (2) through hydrogen donation from the protonated amino group, thus facilitating its removal and formation of enol ii (Scheme 4). This enol adds to the carbonyl group of the aromatic

• band around 350 nm was observed. This increase can be explained by deprotonation of the structures, which facilitates solvation effects by water molecules. The cause for the tautomerism effect at acidic pH may be due to the protonation of the basic site of the amino group present in the derivatives

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• from glutaric anhydride [30]. In fact, molecular dynamics simulations did confirm that the amide carbonyl of the linker forms a stable H-bond to the amino group of C (Figure 7C). Since the distal guanosine in the C–G base pair is a mismatch with the isoorotic acid binding moiety, the isoorotamide

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• morpholine via an aza-Michael addition and condensation (Scheme 3). It was envisaged that the β-amino group could act as a stable functional group resulting in Baylis–Hillman-like reactivity. An extensive survey of reaction conditions using Selectfluor and N-fluorobenzenesulfonimide (NFSI) as the sources of

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• quinazolinone's amino group. When this carbon atom was in a sp2 hybridization state, the C3 position of the indole attacked the inner side of the triple bond under the action of a gold catalyst, leading to a 6-exo-dig cyclization to yield 1,2-fused quinazolinones 146 (Scheme 30, path a). When the carbon atom was

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

• below. Molecular modeling studies First, molecular modeling experiments suggested that our initial hypothesis was correct: the most potent compound VS-77 seems actually able to form a salt bridge with lysine 241, since the acid is located close to the amino group of this lysine (about 3 Å, Figure 5

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• ), compound 154 underwent epoxidation followed by acid-mediated cyclization to yield bicyclic compound 155. The synthesis was completed through a nine-step conversion of 155 to obtain (−)-dysiherbaine (156). To construct the asymmetric quaternary carbon centers with an amino group, the Kang group developed a

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• enantioselective synthesis of planarly chiral macrocycles through a dynamic kinetic resolution approach [15]. Despite bearing an amino group on the phenyl ring, the configuration of the macrocyclic paracyclophane 32 was found to be unstable at room temperature. Consequently, by employing a CPA-catalyzed asymmetric

• chirality transfer process. Notably, while only the amino group of the co-catalysts was shown to engage in the catalytic cycle, the 2-acyl group of 73 was believed to participate in hydrogen bonding interactions with the substrate and the CPA catalyst, playing additional crucial roles. In addition to

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• -protected amino group. On the basis of the previous report [28], a possible reaction mechanism is presented in Scheme 3. The reaction of triphenylphosphine oxide and triflic anhydride first generates an activating agent, the Hendrickson reagent (A). The amide in cyclohexane-1,2-dicarboxamides 4

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• changes in the position and shape of the νNH2 and δNH2 bands are observed, which are an indirect indication of the interaction of the amino group with the metal (curve b) [51]. On the other hand, major changes are observed in the spectrum of 5 wt % Si –MonoAm-Cu(II) (curve d). These are particularly

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• acceptors is more pronounced. The effect of the amino group is stronger comparing to NMe2 due to the steric hindrance in the latter. Since in 1 the azo group, an acceptor, is placed on position 8, it is also expended to bring additional inherent stabilization of the 1K tautomer. The effect of the

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• amino group. The corresponding fluorescence quantum yields were also strongly affected by the substitution pattern of the pyrrolouracils. Compounds 4k and 4l show very high fluorescence quantum yields of 83% and 71%, respectively, what might be reasoned by the strong donor ability of the NMe2-functional

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• -monomethylation of the primary amino group of compound 25 by alkylation with methyl iodide or by Eschweiler–Clarke reductive amination with formaldehyde and formic acid were unsuccessful, because the dimethylated byproduct was also formed, even when one equivalent alkylating agent was used. Finally, our efforts

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ]. In 2015, García-Valverde and co-workers described an alternative synthesis of benzo[e][1,4]diazepines 6, exploring the nitro group of 2-nitrobenzoic acid as a masked amino group. The release was achieved through the post-Ugi reduction of the nitro group with SnCl2 triggering concomitant

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• enhanced electrophilicity of palladium facilitates preferential coordination with the amino group and activates the alkyne to form the intermediate Int-14 instead of Int-14'. Subsequent nucleophilic cyclization generates intermediate Int-15. Following CO insertion, complex Int-16 is formed, and reductive

• the hydroxy group to form complex Int-17 and the amino group undergoes nucleophilic attack to generate Int-18. After CO insertion complex Int-19 is produced and reductive elimination ultimately affords the indolo[3,2-c]coumarin product 10. In 2023, the Garg group achieved the first example of

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• coupling between the secondary amino proton and the proton resonance at 2.76 ppm (see Supporting Information File 1). Therefore, the doublet resonance signal at 2.76 ppm correlates to three protons from the methyl group (CH3) directly bonded to the nitrogen atom of the secondary amino group (NH

• -hybridized carbon atom directly bonded to the nitrogen atom of the secondary amino group of compound 5a. In the structure of each pyrrolidine-2,3-dione derivative 3a–e, there is an α,β-unsaturated ketone moiety in which the π systems of the C=C and C=O bonds could overlap each other to yield an extended

• a dihedral angle of 49.86(10) 86.22(11)° with the phenyl rings C6–C11 and C18–C23, respectively. The angle between both phenyl rings is 70.76(11)°. The stereochemistry around the double bond is Z, allowing an intramolecular N–H···O hydrogen bond between one of the carbonyl oxygen atoms and the amino

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorophores that provide the parent HBC530 ((4-((2-hydroxyethyl)(methyl)amino)benzylidene)cyanophenylacetonitrile) stilbene core [7] but offer an electrophilic alkyl handle on the amino group replacing the original N-hydroxyethyl residue. Three of them have been applied in the cellular applications (Brc3HBC

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

• that features both an ester moiety and an amino group will be discussed later, in section 5 of this review [112]. 4 Sugars We have examined several classes of molecules of gradually increasing complexity, progressing from alkanes (section 1) to ethers (section 2) and then alcohols (section 3

• is that the amino group becomes less basic when an inductively electron-withdrawing fluorine atom is nearby. This effect can be exploited to adjust the charge-state of a drug molecule, which can help in optimising the drug’s target-binding and/or bioavailability [154][173][174][175][176][177][178

• their proximity to the amino group. But there is another aspect to the modulation of pKaH of amines by fluorine: conformation matters, too [182]. If the F–C–C–N alignment is gauche (as in 105, Figure 11), the pKaH will be lowered by ≈1 log unit compared to the non-fluorinated amine. However, if the F–C

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

• tripeptides 2–7 consisting of one tryptophan and two alanine residues. We varied the position of the tryptophan in the peptide sequence, N-terminus in 2, middle of the chain in 3, and C-terminus in 4 to check if this affects their binding by 1. To probe the importance of the N-terminal amino group in the

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• chain length [21]. The exchange by an amino group showed a similar trend, however, N,N-dimethylation of the amino group again increased cytotoxicity significantly [20]. Nevertheless, this cryptophycin might only be conjugated via an ammonium-based self-immolative linker [22]. We envisioned the synthesis

• containing a dimethylamino motif did not require an additional protecting group, ring closure was performed through alkene cross metathesis, which has been accomplished reliably and with good yields for other cryptophycins [11][26][27]. However, for the synthesis of a cryptophycin with a monomethylated amino

• group in unit B a suitable protecting group, i.e., allyloxycarbonyl (Alloc), must be used. Since the presence of this allylic double bond would most likely interfere with a clean reaction outcome after alkene cross metathesis, we decided for a more classical ring-closure strategy through

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• pH 7.4 compared to 41% in acetonitrile, while in acidic aqueous media a PSS of 62% E for the Z→E photoisomerization was observed. This is due to the complete protonation of the amino group converting it to an electron-deficient substituent. The thermal half-lives of 13 and 21 increase by a factor of

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• , making them more oxidizing. Extended conjugation in cyanins (e.g., 53 and 54) further increases their oxidizing nature at the ground state. Overall, both central substitution and extended conjugation play crucial roles in determining the redox behavior of these dyes. Cyanins with an amino group on the

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• pathway leading to 13, we strategically designed 2,3-diaminobenzofuran 11 as a suitably functionalized cyclization precursor for the gold(I)-promoted hydroamination, considering the following three factors. Firstly, the appropriate trajectory of the secondary amino group in the benzofuran moiety is

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• installed amino group and a disubstituted amide group at the 2- and 3-positions, respectively, and reacting them with formamide (Scheme 1B). Those synthetic hubs can be rapidly accessed by cyanoacetamide-based MCRs, which is an interesting reaction type that gives access to privileged cores and has been

• the desired thienopyrimidones 5a–e, quinolinopyrimidones 6a–e and indolopyrimidones 7a–e, respectively, as reported in the literature [42][44]. In accordance with the reported mechanism, after the initial formylation of the amino group at position 2, an intramolecular nucleophilic attack by the NH

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• 39 were prepared exploiting the multicomponent reaction by using aminonaphthalenes, CS2 and secondary amines. The mechanism involved the Ullmann-type coupling of the bromo(amino)naphthalene with the dithiocarbamate salt followed by intramolecular nucleophilic attack of the naphthalene amino group to

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• organocatalyst C21 was studied in 2019 (Scheme 21) [44]. A broad range of aniline and phenol substrates was studied. The best results were accomplished with products containing a Boc-protected amino group on the aniline or 2-aminonaphthalene frame (66a–g), achieving very good yields and excellent

• results in one case, providing high cytotoxicity toward the MCF-7 cancer cell line. The stable axial chirality of the products 71 and 73 was confirmed by calculations of the rotational barriers ranging from 30.2 to 46.3 kcal/mol. Kinetic resolution by amino group protection of biaryls (R,S)-74a–r with

• present on the amino group of the 1,3-benzenediamine, lower yields were reported, and substituting the amino group in position 3 for an N-methylamino or N,N-dimethylamino group led to a reduction in the enantioselectivity. Shao et al. developed the first organocatalyzed atroposelective Friedländer