Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• was obtained in 60% overall yield from 20 via sequential global deprotection of the Bn, Cbz, and Bz groups. The structures of the synthetic glycan motifs 1–4 were supported by their 1H and 13C NMR spectra and MALDI–TOF as well as ESI mass spectra. In particular, the anomeric proton signals of 1–4 were

• highlighted in the 1H NMR spectra of synthetic glycans motifs 1–4 (see Supporting Information File 1). Conclusion In summary, the monophosphorylated glycan motifs 1–4 from PI-88 have been collectively synthesized via a one-pot orthogonal glycosylation strategy on the basis of glycosyl PVB, which avoids such

• -pot synthesis of glycans 1 and 2. One-pot synthesis of glycan 3. One-pot synthesis of glycan 4. Supporting Information Supporting Information File 22: Experimental procedures and spectral data for all new compounds including 1H NMR, 13C NMR, and HRMS. Funding The financial support from the National

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• bond rotation was investigated by variable temperature nuclear magnetic resonance (VT-NMR) spectra (Figure 3) in DMSO-d6 [27]. In the case of the molecular form of amidine 1 (Figure 3a), the signals corresponding to the two methyl groups resulting from the amidine E/Z isomerism were observed separately

• not coalesced even at 383 K, indicating that the C–N bond rotation was sufficiently slow on the NMR time scale (Figure 3b). To separate each E/Z isomer, amidine 2 with two different substituents on the same nitrogen atom, was prepared, and racemic 2 was analyzed by reversed-phase high performance

• details, see Supporting Information File 1). The NMR and HPLC experiments clearly indicate that protonation of the amidine moiety increases the rotational barrier of the C–N bond, a result which is consistent with our DFT study. Since it was found that the E/Z isomers of amidine could be isolated as a TFA

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• , along with decamer 3 (30%). High-resolution atmospheric-pressure-chemical-ionization time-of-flight mass-spectrometry (HR-APCI-TOF-MS) showed a molecular ion peak for 4 at m/z = 1479.4320 (calcd for C100H66N6S4, m/z = 1479.4305). The 1H NMR spectrum of 4 in acetone-d6 exhibited two NH signals at 9.07

• and evaporation of the solvent to afford a crude product, which was recrystallized from THF to give 5 in 58% yield. Due to its poor solubility in common organic solvents, the 1H NMR spectrum could only be recorded in DMSO. At room temperature, the 1H NMR spectrum in DMSO-d6 exhibited broad signals in

• the range of 6–7 ppm, which sharpened significantly at 100 °C (Figure 3). The 1H NMR spectrum at 100 °C displayed distinct signals at 12.01 and 11.54 ppm due to NH protons, a singlet for the pyrrole β-protons at 6.97 ppm, and doublets for the thiophene β-protons at 6.26 and 5.95 ppm. HR-APCI-TOF-MS

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• form two new carbon–heteroatom bonds in a 1,2,4-oxadiazoline ring through both variants of orbital overlap. It should be noted that, in this case, NMR spectroscopy is not applicable to assign the product structure due to the presence of only quaternary carbon atoms in the tetrasubstituted 1,2,4

• -substituted aromatic group, we have observed atropoisomerism (Figure 2) what is manifested by the appearance of a second set of signals in their NMR spectra. As the previously studied similar structures (Y = N–R) [22], products 5b and 5d (Y = O) were formed through the addition of a dipole molecule, resulting

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• Supporting Information File 1. 1H, 13C, and 19F NMR spectra were collected on a Bruker Avance 300 MHz or Bruker Avance-III 500 MHz instrument and processed by MestReNova v. 14.3.1-31739 (2022) MestreLab Research S. L. GC analyses were performed on an HP 5890 N Series II instrument with Restek RTX®-50

• . Its purification was performed by vacuum distillation (18–20 mmHg, 114–116 °C) and stored under argon before subsequent use. The purity (>99.99%) was checked by 1H and 13C NMR spectroscopy. 1H NMR (300 MHz, CDCl3, TMS) δ 5.10 (s, 1H, CH), 4.71 (s, 1H, CH), 4.05 (d, J = 7.3 Hz, 1H, CH), 3.96 (t, J

• = 6.3 Hz, 1H, CH), 2.73–2.02 (m, 4H, CH2); 13C NMR (75 MHz, CDCl3, TMS) δ 200.3 (CO), 101.5 (CH), 73.1 (CH), 67.6 (CH2), 31.1 (CH2), 29.9 (CH2). The NMR data correspond to the published results. Methyl 4-methoxyvalerate and ethyl 4-ethoxyvalerate were prepared using the published method [47]. The

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• oxidative state PC1* that interacts with morpholine (8a) to generate the corresponding aminium radical cation. To gain a better understanding of the process, the formation of the enaminone product 9a was monitored overtime by 1H NMR, which confirmed that the the reaction was complete within 2 h. Furthermore

• : Additional optimization details, mechanistic studies, experimental details, characterization data and NMR spectra for enaminones 9. Acknowledgements We would like to thank Prof. Jose Manuel Costa-Fernández for his help with the spectroscopic studies. Funding This work has received financial support from MCI

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• (≥98% purity) from Sigma-Aldrich. All of these were used as received. 4,4’-Dimethoxyazobenzene was synthesized according to the reaction depicted in Scheme S1 in Supporting Information File 1. The purity was confirmed by NMR spectroscopy (JNM-ECZR 500, JEOL). UV–vis measurements were done with a Cary

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• initial ethyl esters were observed in the NMR spectra of the reaction mixtures. Remarkably, ethyl 2-bromopropanoate (4d) reacted less successfully in the transesterification and the yield of methyl ester 5d within 2 h was 66%, even when the catalyst loading was increased to 5 wt %. The transesterification

• of NMR spectra. Acknowledgements The authors gratefully acknowledge the Magnetic Resonance Research Centre, Centre for Chemical Analysis and Materials Research, X-ray Diffraction Research Centre of Research Park of Saint Petersburg State University. Funding This work was financially supported by

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• analysis of the isolated products of S–H and N–H insertion was carried out based on spectroscopic data (1H and 13C NMR) and the structures of two representatives were established by using the X-ray single crystal diffraction analysis method. Biological activity (cytotoxicity) of some selected products

• was typically carried out at 45 °C in THF solution, and evolution of N2 was monitored using a nitrometer connected with the reaction flask. When the evolution of the gas was completed, the solvent was evaporated, and the crude residue was checked by means of 1H NMR. Two high-field shifted singlets

• CH2Cl2 led to isolation of a colorless, crystalline material with a narrow melting point of 107‒109 °C (yield 66%). The 1H NMR spectrum registered for the purified product perfectly fitted with that one of the crude mixture and thereby confirmed formation of a single product with a single set of the Me‒S

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• (≈120°), the angle between the vectors. The intermolecular distance obtained from STM corresponds to the lateral length of the EEE isomer (F to F distance is 22.06 Å). Thus, we conclude that the adlayer is formed by the energetically most favorable EEE isomer. This is also consistent with the NMR data

• (CRG/2023/003861). We are thankful to IISER Mohali for the departmental and central research facilities and other instruments (NMR, and HRMS NMR facility). HM and TGG would like to thank MeitY for research fellowships within Visvesvaraya Ph.D. Scheme (MEITY-PHD-826). D. G., and A. K. G thank MoE, and S

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• -center of analytical and testing center, Huazhong University of Science and Technology for measuring NMR spectroscopic data. The authors are very grateful to Professor Hideaki Oikawa (Hokkaido University, Sapporo, Japan) for providing A. oryzae NSAR1 heterologous expression system. Funding This work was

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• ones [31][32][33] introducing the photocatalyst [Ru(bpy)3](PF6)2, which successfully initiated the reaction under blue light irradiation and afforded benzamide 2aa in 36% yield (Table 1, entry 2). In that case less than 2% of the iodonium salt 1a remained in the reaction medium according to the 1H NMR

• conditions: 2-isocyano-1,3-dimethylbenzene (0.2 mmol), iodonium salt 1 (0.2 mmol), Na2CO3 (0.34 mmol), [Ru(bpy)3](PF6)2 (0.004 mmol), MeCN (2 mL), H2O (200 μL), under irradiation by blue LED (465 nm, 20 W) for 10 h. bDetermined by 1H NMR spectroscopy after isolation as a mixture of amides or a single amide

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

• -formylpiperidine and aminophenol (2a-o-hydrol) (see Figure 1a). To better understand the influence of the reaction conditions on product distribution, we plotted conversion versus selectivity in Figure 1b. Crudes were analysed by 1H NMR spectroscopy, as shown in Figure S1 (Supporting Information File 1), to

• Scheme S1 in Supporting Information File 1). The 1H NMR spectrum of the crude showed that the starting material was almost completely converted (by 77.4%), that the intermediate 2a-o was recovered in the mixture at 64% and that the side product was detected at only 0.7%. To more deeply understand the

• in the presence of Si-MonoAm-Cu(I) 5 wt %. Under these conditions, the yield was quantitative, and NMR analysis confirmed the exclusive formation of the desired product. No improvements were observed when the catalyst was loaded at 3 or 9 wt % (Table 3, entries 7–10). For comparison, the reaction was

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• yield of 50%. In addition, the reaction furnished bis-olefin 5 in 2% isolated yield which is lower than the estimated yield by 1H NMR measurement of the crude mixture (11%). This is due to the partial loss of the product during purification to remove a trace amount of DBC 2, which was generated as a

• byproduct and exhibited similar polarity as compound 5. The obtained compounds 3, 4, and 5 were identified using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) (see Supporting Information File 1) as well as single crystal X-ray diffraction analysis (vide infra). Furthermore, the

• internally functionalized DBC derivatives [22]. The dihedral angle between the mean planes of the two terminal benzene units is 83°, which is comparable to those of other derivatives. Next, products 3 and 5 were analyzed by variable temperature (VT) 1H NMR spectroscopy. The 1H NMR spectrum of bis-olefin 5 in

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

• stabilization of the azo tautomer and making possible long range proton transfer to the quinolyl nitrogen atom. Keywords: azo dyes; E/Z isomerization; DFT; NMR; photochemistry; proton transfer; tautomerism; UV–vis; Introduction Azo compounds have long been utilized as dyes in industries such as textiles

• OH functionality in compound 2 gives possibility to influence the tautomerism in this compound dynamically by protonation/deprotonation. The tautomeric and switching properties of compounds 1 and 2 have been revealed by using quantum-chemical calculations, UV–vis and NMR spectroscopy and UV

• addition of water to acetonitrile (Figure 3) lead to increase of the content of the keto tautomers, but the enol form is still present. As suggested by the theoretically predicted chemical shifts of the tautomeric proton (Table 1), the use of NMR could shed more light on the tautomeric composition in

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• larger or even commercial scale. The structures of compounds 3 were confirmed by 1H and 13C NMR spectroscopy and high-resolution mass spectrometry. The 1H NMR spectra are characterized by signals from protons of the aromatic rings in the range of 8.08–7.32 ppm, singlets for the proton at the C-3 position

• of the 2,3-dihydro-1,2-thiazole ring in the range of 6.44–6.06 ppm, and multiplets corresponding to the morpholine fragment in the range of 3.80–2.89 ppm or protons of residues of other amino groups in the range of 3.51–1.31 ppm. In the 13C NMR spectra, characteristic signals of the C-4 atom of the

• Information Supporting Information File 15: Full experimental details and characterization data of all new compounds. Supporting Information File 16: Copies of NMR and HRMS spectra of all new compounds. Funding We gratefully acknowledge financial support of this work by the Russian Science Foundation

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

• new natural products, pseudomonins D–G (1–4) isolated alongside other three known compounds, pseudomonine (5), pseudomonin B (6) and salicylic acid (7), were elucidated based on high-resolution mass spectrometry, 1D and 2D NMR analyses. The absolute configurations of the threonine residue in compounds

• unsaturation, calcd. for C11H12NO5, 238.0721) of 1 was established from negative mode high-resolution electrospray ionisation (HRESI) mass spectrum data which showed a deprotonated molecular ion, [M − H]−1 at m/z 238.0723. The complete analysis of 1D and 2D NMR spectra (see Table 1 and Supporting Information

• 1,2-disubstituted benzene ring system was identified by the 1H NMR spectrum showing downfield methine protons at δH 7.88 (dd, J = 8.0, 1.5 Hz, H-5), 7.37 (td, J = 8.0, 1.5 Hz, H-3) 7.01 (d, J = 8.0 Hz, H-2) and 6.92 (t, J = 8.0, H-4) that were consistent with a salicylic acid unit. This was supported

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

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• optical absorption. The UV–vis absorption spectra, fluorescence properties and 1H NMR spectroscopy, indicate that 150 and 151 can be protonated to form the corresponding tropylium cation and consecutive dication under acidic conditions, with reversible protonation−deprotonation capabilities. Additionally

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• (lit. 155 °C [5]). 1H NMR (300 MHz, CDCl3) δ 5.24 (s, 2H), 6.43 (s, 1H), 6.92–7.04 (m, 3H), 7.09–7.16 (m, 3H), 7.19–7.29 (m, 4H), 7.57 (dd, 3J = 7.7 Hz, 4J = 1.3 Hz, 1H), 7.73–7.83 (m, 2H); MALDI–TOF–MS (m/z): 362.2, [C22H16FNOS + H]+. Retrosynthetic analysis of aroyl-S,N-ketene acetals 1 and tentative

• condensation synthesis of aroyl-S,N-ketene acetals 1 under standard (A)a and modified conditions Bb and Cc. Supporting Information Supporting Information File 6: Experimental details of the synthesis and analytical data of compounds 1 and 3, 1H and 13C NMR spectra of compounds 1 and 3. Acknowledgements We

• thank the CeMSA @ HHU (Center for Molecular and Structural Analytics @ Heinrich Heine University) for recording mass spectrometric and NMR spectroscopic data. Funding The authors are grateful to the Fonds der Chemischen Industrie for financial support (J.K. for a scholarship; T.J.J.M. for ad personam

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• . Experimental General: In all experiments rt stands for 22–25 °C. 1H and 13C NMR spectra were recorded on Bruker AVANCE II 300, Bruker Fourier 300HD (300.13 MHz for 1H, 75.47 MHz for 13C and 121.49 MHz for 31P, respectively), and Bruker AVANCE II 600 (600.13 MHz for 1H, 150.92 MHz for 13C, 242.93 MHz for 31P

• phosphorylation of enol acetates. Optimization of reaction conditions for the synthesis of β-ketophosphonate 3a from enol acetate 1a and diisopropyl H-phosphonate (2a)a. Supporting Information Supporting Information File 4: Experimental details, compound characterization data, and NMR spectra. Funding This work

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• % yield. Alcohol products, [4.3.3]_CH2OH and [3.3.3]_CH2OH, were then tested in acidic conditions using anhydrous FeCl3 as a Lewis acid. After the reactions, the alcohol proton signals at 1.54–1.58 ppm disappeared in the 1H NMR spectra, and aliphatic carbon ones at 63.1–63.2 ppm were largely up-field

• -shifted to ca. 34 ppm in the 13C NMR spectra due to conversion into methylene groups (Figure 2b and Figures S315 and S316 in Supporting Information File 1). However, all 1H NMR signals were broad, and gel permeation chromatography (GPC) charts indicated broad patterns due to multiple products with varying

• . Despite the stereocontrolled substrate, the resonances in the 1H NMR spectrum of the product remained broad. Therefore, we concluded that these systems were difficult to give specific macrocyclic oligomers but instead provided linear polymers composed of fully π-fused propellanes. After the reactions

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• chromatography with 30:70 EtOAc/hexanes. Product structures were confirmed by 1H and 13C NMR analysis and X-ray crystal structure analysis of 8a. Density functional theory (DFT) calculations DFT computations were conducted utilizing Gaussian 16W with the B3LYP functional and the 6-31G(d,p) basis set [21][22

• -aromatization. Optimization of IMDA and re-aromatization reactions for the preparation of 8a. Supporting Information Supporting Information File 50: General reaction procedures, compound characterization data, and copies of NMR spectra. Conflict of Interest The authors declare no competing financial interest.

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• % yield over three steps. This compound was isolated in its pure form as a white solid after recrystallization from ethanol, confirmed by HPLC and NMR. In parallel, the primary alcohol group of ent-38 was protected as a TBDMS ether, and the acetate group was converted to a tosyl ester by hydrolyzing the

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• undescribed amine analogues 2–15 were fully characterised following 1D/2D NMR, UV, and HRMS data analyses. X-ray crystallographic analysis of crystals obtained from the aminated products 2, 7, 10, and 15 are also reported here. The new library of amine-substituted triazolopyrazines was screened against the

• good yield with this straightforward methodology (and without the need for toluene reflux), and to determine the distribution of products obtained for this synthetic approach, by exhaustive analysis of reaction mixtures by HPLC, MS and NMR. Ultimately, 14 aminated derivatives of 5-chloro-3-(4

• -chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine were synthesised, purified (≥95% purity, determined by 1H and 13C NMR and HPLC–MS analysis) and assayed for in vitro antimalarial activity. Results and Discussion Synthesis of aminated triazolopyrazine analogues The amination of 5-chloro-3-(4-chlorophenyl)-[1,2,4