Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• Liangyu Liu Wanqiu Lu Quanping Guo Zhaoqing Xu Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 West Donggang Road, Lanzhou 730000, China 10.3762/bjoc.21.202 Abstract This study establishes an efficient solid-phase

• scalable methodology overcomes limitations of prior syntheses, enabling biological evaluation. Keywords: Fmoc-solid-phase peptide synthesis (Fmoc-SPPS); head-to-tail cyclization; plant cyclopeptides; Vaccaria segetalis; Introduction Cyclopeptides have garnered significant research interest owing to their

• existing methodologies and the biological significance of the segetalins, we sought to develop an efficient, scalable, and generally applicable solid-phase synthesis strategy for the Vaccaria segetalis cyclopeptide family. Results and Discussion Synthesis strategy and optimization While both solution-phase

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• ]. In the field of anion extraction, there is growing interest in solid-phase substrates functionalized with synthetic macrocyclic receptors. These materials employ a supramolecular approach based on specific host–guest interactions between the immobilized macrocycle and the guest in solution, often

• , exhibiting near-quantitative binding at millimolar concentrations [17]. The lower binding efficiency of BUs attached to the material compared to the free macrocycle in solution can likely be attributed to the heterogeneous nature of the solid-phase system. Moreover, the anion binding ability of BU1 may be

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

• Synthesis and biophysical assays With Db1–Db3 monomers prepared, new nucleobases were incorporated into PNA oligonucleotides (PNA1–PNA3) via solid phase peptide synthesis using Fmoc chemistry on an Expedite 8909 DNA/RNA/PNA synthesizer and following established protocols [40]. Following purification by

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

• series of compounds 34a–c (Scheme 9) which melt upon irradiation with UV light in the solid phase. Upon irradiation with green light, the compounds isomerise back to the solid phase. The large depth of light penetration of these compounds (>1400 µm for both UV and vis light) and the high capacity for

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• as high as 1.51 × 10−3, for chiral emitters at 5 wt % dispersed in a matrix of polymethylmethacrylate (PMMA). Unfortunately, these pillarene-bridged TTM radicals with a TPA donor did not exhibit CPL in solution [78]. This report signifies that CPL is more easily achieved in the solid phase, where

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• L as an anion receptor to extract cesium salts (chloride, nitrate, carbonate, sulfate, and phosphate) from the solid phase into chloroform. Remarkably, Cs3PO4 exhibits the highest extraction efficiency, driven by strong cooperative interactions involving ion-dipole coordination between Cs+ and

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• fluorescence behavior significantly different from those observed in solution. Figure 4 compares absorption and fluorescence spectra between F8-phenacenes and the parent phenacenes in the solid phase. The parent phenacenes displayed sharp and vibrationally resolved fluorescence bands with maxima in the 380–390

• the fluorination. By contrast, in the solid phase, F8PIC, F8FUL, and F87PHEN showed significantly broadened and red-shifted fluorescence bands indicating that the intermolecular interactions in the solid phase were modified by the fluorine substitution. The present results could provide a strategy for

• , and 489 nm. As shown in Table 1, the differences in the fluorescence maxima shifts between the solution and solid phases (ΔλFL and Δν̃FL) are obviously larger for F8-phenacenes than the parent phenacenes. These observations explicitly indicate that the alignment of the phenacene molecules in the solid

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

• < 5%) despite numerous attempts. Conclusion This work described the stereoselective and gram-scale synthesis of a highly attractive palette of fluorinated amino acids prepared for application in solid-phase peptide synthesis. First, two different fluorinated variants of phenylalanine were synthesized

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• develop a method to facilitate the elimination of this impurity. We first attempted scavenging 6 by solid-phase supported amines. Incubating a mixture of 3 and 6 with TentaGel S-NH2 in DMF led to a gradual decrease of 6 over four days. Whereas this method is applicable to removing 9 of different PEG-OH

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• rigorous planning of one-pot glycosylation the role of a neighbouring group and possible effect of remote participating groups comes into play. One-pot glycosylations have also opened the door of the automated oligosaccharide synthesis which applies the principle of solid-phase synthesis [59][60][61][62

• hydrogenation step to yield the product 38 [107]. Compound 37 shows all-1,2-trans glycosidic bonds due to the installed pivaloyl group in the C-2 position. This cyanopivaloyl group is also widely used in solid-phase automated oligosaccharide synthesis [107] for the synthesis of oligorhamnoside derivatives. Thus

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• . In turn, in the IR spectra (KBr) of compounds 7a–f, absorption bands of the ester fragment in the region of 1714–1750 cm−1 and absorption bands of the carbonyl group of the amide fragment in the region of 1674–1688 cm−1 are observed, which suggests the existence of these compounds in the solid phase

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• issue, Manzano et al. [31] have developed a small-footprint portable chemical synthesis platform able to perform liquid and solid phase organic reactions (Figure 2c). The platform utilizes 3D-printed reactors that can be generated on demand based on the targeted reaction and features liquid handling

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

• molecules Aside from an analysis of the BB usage pattern, real NRP-like molecules can be constructed in accordance to the predicted identity and order of the BBs. Brady and co-workers used solid-phase peptide synthesis to convert the predicted NRPs from virtual into reality; they called these molecules

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• the single crystal X-ray structure of 11 (Figure 5), the environment around the ortho-bromo-position is extremely sterically hindered. Figure 5, shows the Br…Br separations in the α2β2-atropsiomer of compound 11 to be 4.3–4.4 Å. While only an illustration of the situation in the solid phase this

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• other snakes except for the proline-derived diketopiperazines. Experimental General procedures IR spectra were recorded on an Agilent Technologies 7890B gas chromatograph coupled to a Dani Instruments DiscovIR DD-FTIR solid phase interface. Chromatography was performed on an Agilent HP5MS capillary

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• beads, the beads can be split into two portions from which one is analyzed by in-gel analysis first to determine the overall labeling and the other portion after on-beads trypsin digest is subjected to LC–MS/MS analysis. The AzKTB reagent can be synthetized by standard solid-phase peptide synthesis

• proteomics, so called single-pot solid-phase enhanced sample preparation (SP3) [125][126]. The workflow can be scaled down readily to low protein amounts and small volumes compatible with the 96 and 384-well plate format fitting to liquid handling robots. An automatization of the protocol indeed lowers the

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• already discussed in section 1.3, Brunschweiger et al. [47] reported the synthesis of DNA–imidazole heterocyclic conjugates by the GBB-3CR. An alternative to the previously discussed encapsulated solution-phase synthesis is the solid-phase approach in which the DNA barcodes are synthesized on CPG

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• . Additionally, stereoselectivity can be achieved by using potassium bis(trimethylsilyl)amide for deprotonation and methylation with MeI [33][39]. Any of these routes would yield methylated amino acids that can then be incorporated into an oligopeptide in solid-phase peptide synthesis (SPPS). Additionally, N

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• addition, the compatibility of the method with solid-phase synthesis is shown exemplarily. Keywords: azide; click reaction; CuAAC; pyrazole; triazene; triazole; Introduction Nitrogen-containing heterocycles are central scaffolds in medicinal chemistry and are incorporated in most small-molecule drugs [1

• systematically. Results and Discussion Triazenes have previously been established as versatile intermediates and linkers for conventional and solid-phase synthesis [22][23][24][25] that can be considered as protected diazonium salts [3]. According to the previous work [3], triazenylpyrazoles could serve as azide

• 21gd could be isolated in quantitative yield with this technique, avoiding additional purification steps for the azide intermediate without any losses in product formation. The developed procedure was exemplarily transferred to solid-phase synthesis. In quantitative yields, 5-methyl-1H-pyrazol-3-amine

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• in Figure 3b, all the materials were analyzed with Raman spectroscopy in the solid phase with normalization at G-band (1570 cm−1) of SWNTs. The characteristic signals from Cu-nanobrackets 1b are observed in e- and i-SWNTs, but not in p-SWNTs, indicating the interlocking of SWNTs with 1b, because the

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• of hydrophilic oligopeptide anchors (oligo-Lys, oligo-Glu, and oligo-Arg) were synthesized. A previously reported Prato reaction adduct of a biscarboxylic acid-substituted C60 derivative was subjected to a solid phase synthesis for amide formation with N-terminal amines of peptides on resin to

• suitable for the coupling to peptides on resin, prepared by solid-phase peptide synthesis (SPPS) [35]. The detailed conditions for the amide-forming reaction were optimized using biscarboxylic acid-substituted C60 derivative 3 and a similar peptide with a primary amine derived from γ-aminobutyric acid

• resin (rink amide MBHA) relative to 3, provided a rather low yield (13%, isolated by HPLC), which was increased to 24% by changing the solid phase to 2-chlorotrityl chloride resin. By replacing the base with N,N-diisopropylethylamine (DIPEA), the yield was slightly increased to 28%, which became higher

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• attention is given to the strategies of mimics formation to demonstrate how biocatalysis provides an elegant link between chemistry and biology. Review Macrocyclic peptides Since first being reported in the 1960s [26], solid-phase peptide synthesis (SPPS) has been an invaluable tool for preparing numerous

• and promote the utilization of TE domains as biocatalysts with tremendous potential. To this purpose, Walsh and co-workers developed the 2nd generation of tyrocidine chemoenzymatic approach utilizing a linear peptide immobilized on the solid-phase support poly(ethylene glycol) acrylate (PEGA) with a

• -product biosynthesis and combinatorial solid-phase chemistry, this strategy has expanded the sequence space of macrocyclic peptides significantly (Scheme 2c). The daptomycins The calcium-dependent antibiotic (CDA, 11), daptomycin (12), and A54145 are acidic lipopeptides isolated from Streptomycetes, which

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• , but the second fluorination step occurs only after reaction for several days. In the solid phase, mechanical milling of the diketone substrate with solid Selectfluor in the presence of sodium carbonate [13][14], and reaction of ketones with a strong base and an N–F reagent give rise to the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36