Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• N1- and N2-transition states with favorable NCIs shown as red dashed lines. Reaction of 18 under conditions A and B (top), and proposed chelation/coordination pathways to account for regioselectivity (bottom); black two-headed curved arrows indicate the observed NOEs of the major product; adetermined

• and N2 transition states with favorable NCIs shown as red dashed lines. DFT-calculated transition-state structures and energies of 21 under conditions A (top) and conditions B (bottom). NMR, NOE, and yield data of compounds 8 and 9. Synthesis of compounds P1 and P2. Reaction of 21 under conditions A

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• -di(het)aryl groups via Suzuki–Miyaura [26][27][28] or Sonogashira [29][30][31] reactions. In this study, we report a straightforward method to obtain a diverse array of N-substituted DPP derivatives through a two-step process. Firstly, the N-alkylation of Pigment Red 254 (DPP 1) is achieved using

• reagents used in this work were purchased from Merck Life Science (Algés, Portugal) or TCI Europe N.V. (Belgium) and were used as received. Pigment Red 254 was purchased from TCI Europe N.V. The solvents were used as received or distilled and dried by standard procedures. Analytical thin-layer

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• results, thiazole 2b, benzothiazole 2i and benzimidazole 2t react very well with sodium nitrite in an acidic environment (Scheme 6, red section). Among the various subclasses of compounds, pyrazole 2l exhibited a high reactivity using t-BuONO and EtONa in ethanol (Scheme 6, red section). On the other hand

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• amine A1 without the lutidine additive (black curve) and after addition of 2 equiv (red curve). DMF, 0.1 M NaOTs, 0.1 V/s, Pt disc electrode, vs Ag/AgCl, KCl(sat.) Semi-differential CV curves for the mediators (TEMPO, bis(4-tert-butylphenyl)nitroxide and tris(4-bromphenyl)amine) and amine A3 in DMF

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

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• days, but it decomposed completely to iodosyl 9 after just 48 hours in dry chloroform-d1 in air (red line in Figure 3). The difference in the stability of difluoroiodane 6 in CDCl3 and CD3CN was attributed to the ability of acetonitrile to coordinate to the iodine(V) centre. Stabilisation via halogen

• (blue line), dry CDCl3 with 2.4 equivalents of dry pyridine (green line), and dry CDCl3 (red line). Order of hydrolytic stability for the four hypervalent iodine(V) fluorides. Examples of fluorination using hypervalent iodine(III) reagents 1 and 2. Preparations and reactions of hypervalent iodine(V

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• = green, N = blue, and O = red. a) Absorption and b) emission spectra of the compounds dissolved in CH2Cl2. Cyclic voltammograms of the compounds collected on ca. 1 mM solutions of the analyte in CH2Cl2 with 0.1 M Bu4NPF6 as electrolyte. The major y-axis tick mark spacing corresponds to 5 μA. Structural

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• . Subsequently, the downstream HR-iPKS module, SorbB, catalyzes both the extension of polyketide chain from 30 using two additional malonyl-CoAs and C-methylations exploiting two units of SAM (S-adenosyl methionine) to generate thioester 31 on the ACP domain. Then, the reduction (Red) domain located at the C

• ][98][99]. The reduction (Red) domain at the C-terminus of SfmC reduces the thioester 87 to release aldehyde 88 from SfmB, while the adenylation (A) domain activates 86 and loads it onto the PCP domain of SfmC. The Pictet–Spengler (PS) domain then catalyzes the first diastereoselective PS cyclization

• to form bicyclic thioester 89 with incorporation of a stereogenic center at C1. The Red domain liberates bicyclic aldehyde 90 by reducing the resulting thioester 89, while the A domain again activates another molecule of tyrosine derivative 86, facilitating its loading onto the PCP domain. In the

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• was added, no significant shifts in the NMR spectral signals were detected, probably due to the poor solubility of the iodane. Conversely, with the addition of the red tetrazine salt 1c, a significant downfield shift was observed for the alpha-carbon protons from 3.51 ppm to 4.55 ppm, as illustrated

• formation of a) an alkoxy-NHI which is causing a significant downfield shift of the protons in alpha-position (orange) compared to the free alcohol 2 (blue) and b) oxidation of p-tolylmethanol (3a, blue) to the aldehyde 4a (green) and carboxylic acid 4a’ (red). Reaction conditions: An equimolar mixture of

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

• . There are several options for chemical methylation (see text), but only one example is shown. Enzymatic synthesis is highlighted in red as this is the focus of this highlight. PURE = protein synthesis using recombinant elements, MT = methyltransferase. Biological methylation. A) Methyl donors from

• , PDB ID: 6UAK (https://doi.org/10.2210/pdb6UAK/pdb), [72]. The residues involved in SAH binding are depicted in red. Reaction scheme of the PAMT´s catalysis, leading to the enzymatic conversion of aspartate to aspartyl-O-methyl ester, followed by a two-step non-enzymatic conversion via succinimide

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• from Microbulbifer Agarases Agarose is a natural polymer consisting of a linear chain of alternating residues of 3-O-linked β-ᴅ-galactopyranose and 4-O-linked 3,6-anhydro-α-ʟ-galactose. Agarose is a major component of agar, a polysaccharide present in the cell walls of some red algae [101]. Agarases

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• supramolecular structural transformations [37]. The large-aspect-ratio DA nanostructures assembled into macroscopic soft scaffolds, for which the disassembly process on a macroscopic length scale was controlled by white light. Furthermore, the red-light-responsiveness of the DAs could be regained in aqueous

• (Figure 1a). Upon 625 nm red-light irradiation for 60 s at 20 °C to reach the photostationary state (PSS), the strong absorption band at 470–685 nm was diminished, with a clear isosbestic point at 259 nm (Figure 1a, red line), which indicates a selective photoisomerization process from the open-isomer O

• -DA11 (Figure 1a, black line and Figure 1b blue line) to the cyclized-isomer C-DA11 (Figure 1a, red line). The resulting solution continued to be irradiate with 625 nm red light for 60 s at 20 °C and subsequently stored in the dark at 20 °C for 60 min for the thermal back reaction to occur to test the

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• fluorescein sample was adjusted to 6.30 min to correct for run to run drifts in retention time. Biosynthetic scheme for the formation of burpitides using a split (top) or fused (bottom) pathway. RS is recognition sequence. Peptide modifications are shown in red. Cladogram made from 647 plant species surveyed

• color-coded to show localization of various molecules. Molecules in red are new to this study and predicted by MS/MS fragmentation. Ceanothine B was isolated and its structure confirmed by 1D and 2D NMR. Correlations are indicated as follows: red lines – COSY, green lines – TOCSY, pink arrows – NOSEY

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• -catalysed bidentate-directed benzylic C(sp3)–H fluorination. Palladium-catalysed benzylic fluorination using a transient directing group approach. Ratio refers to fluorination (red) vs oxygenation (blue) product. Outline for benzylic C(sp3)–H fluorination via radical intermediates. Iron(II)-catalysed

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• decreases concomitantly to the appearance of two new bands at 312 and 438 nm (Figure 2, blue line). Two isosbestic points can also be observed at 310 and 429 nm. The back Z→E photoisomerization can be achieved by illumination at 485 nm (Figure 2, red line). 1H NMR spectroscopy has been used to determine the

• ). The S-galactosyl azobenzenes 3–5 also displayed excellent photoswitching properties, with a red shift for the π→π* transition (λmax = 348–364 nm) compared to the O-galactosyl derivatives (Table 1, entries 5–8). However, the absorption coefficient and the thermostability of the Z-isomers are increased

• ) designed general structure of photoswitchable ligands 1–5 targeting LecA. (Left) Absorption spectra and (right) fatigue resistance of 1 under alternated 370/485 nm irradiations in Tris buffer/DMSO 95:5 at rt: E-1 (black line), PSS370 (blue line), PSS485 (red line). Irradiation conditions at 370 nm: 12.8

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• rings. The triangles indicate a product having α-substituents. (c) Crystal structure of DH-ER-KR tridomain (PDB ID 8G7W) [24]. DH, KRS, ER, KRC are colored in cyan, pink, yellow, and purple, respectively. The lid of KR catalytic pocket is colored in red. The co-crystallized cofactor is represented as

• classification of their products. The key catalytic residues are marked by red stars, and the NADPH-binding residues (partially) are marked by blue triangles. The numbers at the top indicate the fingerprint motifs. Sequence logo comparation of γ- and δ-module KRC based on the classification of their products

• . Top five rows show KRs associated with an inactive DH that produces the hydroxy products. The key catalytic residues are marked by red stars, and the NADPH-binding residues (partially) are marked by blue triangles. The motif numbers at the top are corresponding to the location of fingerprints in

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• diterpenoids and their biosyntheses. (A) The 6/10-bicyclic hydrocarbon framework is conserved in eunicellane diterpenoids. Selected natural products consisting of cis- (red) and trans-eunicellane skeletons (blue) are shown. (B) Four types of diterpene synthases are known to form the eunicellane skeleton, each

• of DFT calculations on the atropisomers 10a/10b and the free energy barriers for clockwise (blue) and counter-clockwise (red) rotations. Scaffold exploration of the 2E-trans-eunicellane skeleton. Supporting Information Supporting Information File 90: Experimental methods, NMR and MS spectra, and

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

• complexation, a significant red-shift of the dipyrrin band to 465 nm was observed due to the metal coordination with the dipyrrin moieties in 4b. To compare the structures of 1a and 1b, they are calculated through geometry optimization with the density functional theory (DFT) method. The alkyl chains at the

• existence of SWNTs in the extract. Actually, the absorption bands in the range of 500–1400 nm are attributed to the extracted SWNTs. The absorption band of Cu-nanobrackets 1b is red-shifted from 465 to 495 nm in the extract, suggesting the complexation of 1b with SWNTs. To further investigate whether the

• p-SWNTs. Red and black characters indicate metallic and semiconducting SWNTs, respectively. (a, b) Enriched (n,m)-SWNTs are shown in orange. (a) Binding energy between SWNTs of various (n,m)-structures with Cu-nanobrackets 1a and 1b; GFN2-xTB-optimized structures of (b) 1a@(9,4)-SWNT and (c) 1b

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• start at 0 V. Structures of the imidazolium cations obtained by DFT calculations (B3LYP/6-311++G (d,p)). The electrostatic potentials are indicated by color (blue: positive; red: negative). Overview of the synthesis of compounds 1–63. Thermal decomposition point at 5% mass loss in °C for NTf2− TAAILs 37

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• future. Characterization data. (a) FTIR spectra of t-Bu-FIDO and t-Bu-FIDS. (b) UV–vis spectra of fullerene derivatives normalized at 270 nm. (c) Vacuum TGA curves of t-Bu-FIDO (black), t-Bu-FIDS (red), and C60 (blue). The measurements were conducted under 0.1 Pa. (d) HPLC analyses before deposition of t

• -Bu-FIDS (black) and of toluene used to rinse the evaporated film of t-Bu-FIDS (red). Single-crystal structure of t-Bu-FIDS. (a) The π–π distance between two molecules. (b) Crystal packing. Cyclic voltammograms of fullerene derivatives in o-DCB solution containing Bu4N+(CF3SO2)2N− (0.1 M) as

• supporting electrolyte at 25 °C with a scan rate of 0.05 V/s, for C60 (blue), t-Bu-FIDO (red), and t-Bu-FIDS (black). Glassy carbon, platinum wire, and Ag/Ag+ electrodes were used as the working, counter, and reference electrodes, respectively. J–V curves of BHJ OPV devices. (a) ITO/ZnO/fullerene:P3HT (1:1

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• under otherwise identical conditions gave a completely different spectrum (Figure 1B, red) and we assume that the triplet state of Aza-H is almost fully quenched by oxygen at the selected delay, which is supported by additional kinetic measurements (see below). The second transient species is identified

• Aza-H•+ (red) were computed using TD-DFT (see Supporting Information File 1 for details). These computational results, which are included in Figure 1B, align well with the experimentally observed absorption bands in the visible region, supporting our assignment. The observed behavior of the Aza-H

• contribution of the radical cation to the TA signal at 640 nm is only minor, which allows us to estimate a triplet lifetime of ≈28 µs at this detection wavelength. Based on our observations, an isolated triplet spectrum can be obtained from the spectral difference between the black and the red spectrum in

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• ]. Carboxylic acids 2 and aldehydes/ketones 3 used in the Ugi4CR. GI50 range plot against human solid tumor cell lines of investigated α-acetamide carboxamide isatin hybrids. Green most potent, yellow intermediate, red less potent. (A) Library of isatin-based α-acetamide carboxamide oxindole derivatives

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• shown. (b) Packing structures. Chloroform molecules in the crystal of 3b are omitted for clarity. X-ray charge density analyses of 3a and [6]CMP. (a) Deformation map (Fo – Fc) of a pyridine ring in 3a (contour interval: 0.05 e·Å−3, positive: red, negative: blue). (b) Electrostatic potential maps mapped

• on the 0.0067 e·Å−3 isosurface for the electron density. Response towards acid treatment with nitrogen-doped CMPs. (a) Absorption spectra of 3a (CHCl3, 2.3 × 10−6 M) in the absence (black) and presence of trifluoroacetic acid (green: 4.3 × 10−2 M, blue: 2.1 × 10−1 M, red: 4.2 × 10−1 M). (b

• ) Absorption spectra of 6 (CHCl3, 1.9 × 10−6 M) in the absence (black) and presence of trifluoroacetic acid (green: 4.3 × 10−2 M, blue: 2.1 × 10−1 M, red: 4.2 × 10−1 M). Syntheses of 3a and 3b. Supporting Information Supporting Information File 50: Experimental and copies of spectra. Supporting Information

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• + ʟ-isoleucine; (i) 8 + JadG; (j) 8 + AlpJ + ʟ-isoleucine. UV absorptions at 266 nm (black line) and 313 nm (red line) are displayed for each reaction. HPLC traces of reactions of JadG, AlpJ, or Flu17 quenched by SOD. (a) 8 + JadG + ʟ-isoleucine; (b) 8 + JadG + ʟ-isoleucine + SOD (5,000 U/mL); (c) 8

• + AlpJ; (d) 8 + AlpJ + SOD (5,000 U/mL); (e) 8 + Flu17 + SOD (5,000 U/mL). UV absorption at 266 nm (black line) and 313 nm (red line) are displayed for each reaction. Ring cleavage and ring rearrangement reactions in the biosynthesis of atypical angucyclines. Proposed catalytic mechanism of cofactor

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• electron density (ρ) and the reduced-density gradient (RDG, s). The NCIplot provides qualitative information, and it can successfully map real-space regions where non-covalent interactions are prominent. The resulting plots have a color scheme of red–green–blue scale, where red represents attractive