Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• intermolecular interactions in biological environments. This study clarifies the electronic origin of DFMO’s gauche effect and provides insight into how local electronic factors determine the structure of fluorinated amino acid derivatives. Keywords: conformational analysis; difluoromethylornithine; gauche

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• utilization in metal-chelating agents, flame retardants, and catalysts [3][6][7][8][9][10][11][12][13][14]. However, these applications involved the use of either phytic acid itself or its derivatives. Our group has previously reported a method for synthesizing diaryl phosphates using phosphoric acid as the

• the corresponding free acids or sodium salts [15][46][47][48]. According to Figure 3, each diaryl phosphate was isolated with a yield of approximately 60%, except for some derivatives. It was presumed that 2-hydroxy-m-xylol (1c) having methyl groups at the ortho-positions, led to a diminished yield of

• recovery of 4.2%, and phosphate ester 2a was synthesized using the extracted phytic acid in a good yield (Scheme 4). Furthermore, we demonstrated that the reaction could be applied to phenol derivatives (Figure 3). The time-course analysis of the esterification process via 31P NMR (Scheme 3, Figure 4

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• -functionalization, where a bulkier handle provides the required enantiomerization barrier to screw helical chirality (Figure 1C and D). A straight forward preparation of various carbohelicenes via an organocatalytic enantioselective hydroamination reaction of polyaromatic phenols with diazodicarboxamide derivatives

• further transformed into representative derivatives. Notably, the reaction performed well in the scale-up demonstration and the post-synthetic transformations proceeded smoothly without hampering the enantiomeric excess (Scheme 2). Another report applying peri-C–H functionalization for the synthesis of

• catalysts [33]. A domino reaction was developed, beginning with a PPS L2-catalyzed Michael addition of phosphine oxides 7 to nitro-substituted oxa[5]helicenes 6, followed by a copper-promoted aromatization. This sequence efficiently produced phosphorus-containing oxa[5]helicene derivatives 8 in high yields

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• , Leuven B-3001, Belgium 10.3762/bjoc.22.13 Abstract Solvent-dependent transformations of polysubstituted 2-acetyl-2,5-dihydrothiophenes to the corresponding 2-hydroxy- or deacetylated derivatives are described. The treatment of a methanolic solution of the dihydrothiophene substrates with sodium

• ] and more complex molecules [11]. Rearrangements of the oxidized compounds are equally important transformations [12]. Oxidation of compounds containing a carbonyl group into carboxylic acid derivatives can be divided into two large groups: direct oxidation and oxidative rearrangements. Direct

• conditions in hand, we have investigated the oxidation of 2-acetyl-2,5-dihydrothiophenes 1, containing various substituents (Scheme 2). Cyclohexano-, cycloheptano- and cyclooctano-spiroannulated 2-acetyl-3-morpholino-N-phenyl-2,5-dihydrothiophene-2-carboxamides 1a,c,f were oxidized into 2-hydroxy derivatives

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• advantages of inexpensive starting reagents, operationally simple reactions, and minimal purification of intermediates. Moreover, this work reports the successful sulfonation of 6,6’-dibromoindigo, producing water-soluble derivatives of this historically relevant dye. Keywords: 6,6’-dibromoindigo; dye

• indigo derivatives, an increasing number of sulfonic acid groups results in greater solubility of the 6,6’-dibromoindigo derivative (e.g., 10 has greater solubility in water than 9) [25]. When dissolved in aqueous solution, both 9 and 10 yield a bright blue solution. As shown in Figure 1A, salt 10

• red shift by 16 and 15 nm with a moderate increase in molar absorptivity, respectively, for compounds 9 and 10 [29]. This means that to the human eye, di- and trisulfonated derivatives of 1 appear blue, not purple. A smaller shift in λmax is observed when indigo is sulfonated, allowing for its blue

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• aromatic ring were also evaluated. The unsubstituted benzamide-derived sulfenamide 3z reacted smoothly to afford the desired product in 90% yield, serving as a representative standard for comparison. Ortho-substituted substrates were compatible, including 2-chloro (3a’) and 2-bromo (3b’) derivatives which

• were obtained with 87% and 88% yield, respectively, indicating that steric hindrance at the ortho-position does not adversely affect the transformation. Meta- and para-substituted derivatives, regardless of their electronic nature, also reacted smoothly to afford the corresponding products 3c’–g’ in

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• between the catalyst and the reagents. The chirality of the catalysts is derived from either amino acid or amino alcohols (including cinchona alkaloid derivatives). There are three exceptional structures: catalysts A-H and E-H, which are the hydrogen analogues of the corresponding iodine-containing

• % ee, Table 1, entry 6). Aminoindane-based catalysts C and D were inefficient and stereomeric purity of the products were not determined (Table 1, entries 7 and 8). The next group of catalysts consists of amino acid derivatives. The most selective was tert-leucine-based catalyst E affording the Mannich

• ). Screened catalysts. Model for the interaction of the catalyst with the imine. Substrate scope of the asymmetric Mannich reaction. The catalytic Mannich reaction under study. Catalyst screening. Reaction in the presence of catalyst K and its derivatives. Supporting Information Supporting Information File

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• can be shifted in the deep red/NIR region by changing the donor group with increased conjugated systems [19][20][21][22]. Gupta et al. studied optical properties of D–π–A system-based indan-2-one derivatives, and symmetric derivatives showed a significant bathochromic shift (≈300 nm) compared to

• toxic anion and dangerous to human health, by dyes gives advantages such as high sensitivity, fast response, low cost, and ease of operation [26][27][28]. In this study, symmetric novel indan-2-one derivatives with a D–π–A–π–D system were synthesized, and their structures were characterized using 1H NMR

• /acetic acid buffers with a good yield (84%). Target compounds were synthesized by a coupling reaction between 2-(1,3-dihydro-2H-inden-2-ylidene)malononitrile (1) and appropriate alkylaminobenzaldehyde derivatives in acetic anhydride. Compounds were obtained with low to good yields (25–75%, conventional

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• biologically active properties. Thus, barbamide exhibits molluscicidal activity [7], and sintokamide A is active against prostate cancer [8] (Figure 1). As derivatives of strained and unique structure and properties [9][10] cyclopropanes are of interest for entering into various transformations along the path

• groups seems attractive for both theoretical chemistry and the synthesis of 2-aminocyclopropanecarboxylic acids, of which representatives have biologically active properties against kynurenine-3-monooxygenase [25] and GABA receptors [26]. Such aminocyclopropane derivatives can be classified as donor

• a CF3-containing substrate and a nitromethylene component (the tandem reaction of trifluoromethyl-substituted alkenes with nitromethane [34] or bromonitromethane derivatives [35][36]) (Scheme 1). At the same time, one of the methods of synthesis of vicinally substituted nitrocyclopropanes is the

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• . Between 2020 and 2021, the research groups of Zhang [39], Bao [40], Zhou [41], and Glorius [42] reported four different methods for the reductive hydrogenation of pyridine or pyridine derivatives (Scheme 3). By activating pyridine to a pyridinium salt, the hydrogenated product can be efficiently obtained

• partially or fully saturated derivatives [49]. Over the past years, several research groups worldwide have reported significant progress toward addressing these selectivity and reactivity issues (Scheme 5 and Scheme 6). Nevertheless, despite these advances, the field still suffers from fundamental

• catalyst to achieve the hydrogenation of the nitrogen heterocyclic moiety in quinoline, that yielded the target product in near-quantitative amounts [51]. In 2021, the research groups of Sun [52] and Zhang [53] reported the use of iridium or manganese as catalysts to convert quinoline derivatives into

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• corresponding vic-bis(dithiane) derivatives 16a–d. In 2018, Milsmann et al. reported the dimerization of benzyl bromide using a zirconium complex as a photosensitizer (Scheme 4) [14]. Heating a zirconium precursor with the pincer-type ligand 17, which can be synthesized in three steps from commercially

• formation to give the cyclic acetal 33. This transformation was applicable to a range of oxetanes 30a–c bearing benzylic alcohol derivatives, each affording the corresponding cyclic acetals in good yields. In 2023, Ota and Yamaguchi et al. reported the hydrogenation of alkyl chlorides via halogen atom

• strong affinity of zirconium for oxygen atoms [4][21]. Building on this concept, they envisioned that a similar reaction system could be applied to the homolytic cleavage of C–O bonds in alcohols and ethers. When benzyl alcohol and ether derivatives 49 were treated with zirconocene in the presence of a

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• unavailability of other stable cycloheptatrienyl anions until recently, its derivatives were not expected to show high selectivity in reactions. Herein, we present the first examples of selective reactions of low-symmetry hexa(methoxycarbonyl)cycloheptatrienyl anion 2 [20] towards electrophiles. Additionally

• α-position, respectively. Compounds 5 represent derivatives with two substituents at the sp3-carbon atoms which sometimes tend to rearrange into the corresponding norcaradiene derivatives [29][30]. Our reactions of anion 2 with electrophiles confirm this tendency – we always observed either a

• reported [31] halogenations of anion 1 only afforded the corresponding octasubstituted cycloheptatriene derivatives. The reactions of 2 with alkyl halides were selective in terms of the initial reaction – the i-substitution was never observed. However, the alkylation reactions were even more intricate than

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• -rich acetophenone derivatives, such as the p-methoxy-substituted example 34 afforded only low yields. It is noteworthy that performing the synthesis of 26 under neat conditions with an excess of PCl5 afforded substantial amounts of dichloride 41 (Scheme 8A) [57]. Engler showed that the use of a large

• constitutional isomeric chloro derivatives 66 and 67 were formed in a 65:35 ratio. In the case of non-enolizable ketones such as benzophenone, dichlorodiphenylmethane 68 was obtained in 93% yield. Aldehydes consistently afforded gem-dichlorides in excellent yields, regardless of enolizability (not shown). It is

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• substituents that are labile towards electrophiles. Thus, there is a need for new, more efficient methods for the synthesis of nitro-NNO-azoxy derivatives that do not have the disadvantages of the known approach and allow the use of a wide range of substrates, including various aliphatic ones. Recently, our

• Griess test results, all synthesized nitro-NNO-azoxy compounds released high fluxes of NO (36–137%) exceeding those of CAS-1609 (22.1%) and NG (15.3%). Interestingly, azoxy derivatives 2a–e,i showed NO-donor properties only in the presence of ʟ-cysteine proposing the thiol-dependent mechanism of NO

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• -tert-butylbromobenzene [53]. We therefore adopted a prenylation method used by Knölker for bromocarbazole derivatives using Pd2(dba)3 [54]. Pleasingly, this led to the corresponding prenylindoles 14–17 without forming the isomeric reverse prenylated adducts, although the starting material was recovered

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• ]. In general, the developed approach allows pyridone derivatives to be generated in various environments of condensed carbo- and heterocyclic structures. Among the synthesized pyridone derivatives we have found analgesic [20][26], antibacterial [20] and antifungal [20] agents, which show practical

• ], fluopyram [36], and the nematicide fluazaindolisine [37] (Figure 1). The trifluoromethyl piperidine backbone is part of the structure of anticancer [38] and antirheumatic [39] agents. The fluorine-containing pyridines and their heteroannelated derivatives are known to exhibit a high biological potential, on

• minor when heated in 1,4-dioxane (Scheme 3, Table 3). Previously, we proposed and experimentally confirmed an aldol mechanism underlying the three-component cyclization of polyfluoroalkyl-3-oxo esters with α-methylene ketones and amines in piperidone derivatives. According to this mechanism, the key

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• Group, Magyar tudósok krt. 2, H-1117 Budapest, Hungary 10.3762/bjoc.21.205 Abstract New tetra- and pentacyclic derivatives of the dibenzo[c,f][1,2]thiazepine ring system have been synthesized. The target compounds contain methylenedioxy or ethylenedioxy substituents linked to the benzene ring. The key

• step for the construction of the ring systems has been implemented by an intramolecular Friedel–Crafts cyclization. Altogether eight new ring systems are described here, five of them are also characterized by single-crystal X-ray diffraction. Keywords: acylation; bridged derivatives; cyclization

• ; Friedel–Crafts reaction; heterocycles; new ring systems; Introduction In our prior report [1] we disclosed the synthesis of new fused ring derivatives of the dibenzo[c,f][1,2]thiazepine skeleton (1, Figure 1) shown by general structure 2. In recent publications we have also reported the synthesis of new

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

• 10.3762/bjoc.21.203 Abstract Various 5-arylidene derivatives were prepared via a Knoevenagel condensation-type reaction of aromatic/heteroaromatic aldehydes with rhodanine or thiazolidine-2,4-dione (TZD) catalyzed by EDA/AcOH under microwave heating. This convenient methodology is broad in scope (49

• scaffolds for several synthetic or natural compounds [5]. Five-membered heterocycles include the thiazolidinone nucleus, characterized by two heteroatoms and a carbonyl group on the fourth carbon, as seen in compounds like rhodanine and thiazolidine-2,4-dione derivatives (Figure 1). These privileged

• , ciglitazone, and rosiglitazone [9][10]. Rhodanine (2-thioxothiazolidin-4-one) derivatives exhibit a wide range of pharmacological activities, including antiviral [11], antimalarial [12], antimicrobial [13], anti-inflammatory [14], anticancer [15], antidiabetic [16], antibacterial [17], and antifungal [18

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

• leading not only to improved extraction effectivity but also to enhanced selectivity [2]. Anion extractants based on functionalized polystyrene or silica gel typically incorporate calixarenes [6] and their analogues, calixpyrroles [7][8], azacalixarene derivatives [9], or expanded porphyrin-like sapphyrin

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• –C, C–HA bond-forming reactions [36][37]. These chiral NHC catalysts, used to access enantiopure alcohol/amine derivatives, particularly 2° and 3° alcohols/amines, are significant structural motifs in numerous drugs and natural products and have found widespread synthetic applications in medicinal

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

• arylcyclopropanes 5 by applying NHC/ photoredox cooperative organocatalysis under visible-light irradiation. This method allows sequential C–O and C–C bond formation, leading to access to various γ-aroyloxy keto-ester derivatives 6 in good yield up to 81% and excellent functional group tolerance, including electron

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• member ryanodine has a specific regulatory effect on myocardial calcium ion channels (PyR). Since only a limited number of compounds have been reported to act by modifying this receptor, ryanodine and its derivatives are potential therapeutic agents for treating cardiovascular diseases. This article

• polyhydroxylated molecular framework has posed a significant synthetic challenge, impeding the preparation of derivatives for SAR exploration. In 2017, the Reisman group addressed this issue by drawing upon an analysis of Deslongchamps’s prior synthetic work [45] (Scheme 8). They hypothesized that utilizing an

• ryanodine skeleton via an established single-electron reductive cyclization to complete the total synthesis. This strategic inversion of the synthetic sequence enabled direct acylation of anhydroryanodol derivatives, facilitating the introduction of the key pyrrole-2-carboxylate unit. This method

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• functionality strategy employing oxazoline to unmask the 1,2-hydroxyamine moiety proves feasible, eliminating the need for alkene functionalization required in previous endeavours. This current strategy provides a reliable platform for accessing diverse uracil nucleosides and their derivatives, facilitating the

• target-oriented synthesis toward malayamycins remains to be complished and several steps need to be improved, the current strategy provides a reliable platform to access various uracil nucleosides and derivatives for developing potent fungicides. Selected natural uracil-containing nucleosides (the key

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• , and low toxicity make calixarene derivatives valuable drug candidates against cancer. The aim of the present study was the synthesis and characterization of a calix[4]arene derivative in which known anticancer isothiouronium groups were clustered on a calix[4]arene scaffold bearing long C12 alkyl

• chemotherapy and achieving targeted treatments [18][19][20]. In the era of nanotechnology, a promising strategy for developing more effective treatments against cancer [21][22], calixarene derivatives are also emerging as valid building blocks for the development of nanoscale multivalent constructs [23]. Due

• into the calixarene skeleton to develop anticancer derivatives, including proline [34], carbonyl amide [35], glycoureido [36], ureido [37], picolylamine [38], 5-bromopentyltrimethylammonium bromide and 3-bromopropyltriphenylphosphonium bromide [39], among others. Isothiouronium salts represent another

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• -diaryl-1,2,3-triazoles 7–12 into target pentacyclic aromatic heterocycles 13–18. Yields of annulation reactions for naphthalene-containing analog 13 (90%) was appreciably higher than for quinoline and isoquinoline derivatives 14–18 (31–72%). Due to triazole subunit connectivity to the napththalene

• thermal heating conditions [46] was successful for preparing these compounds. Yields of annulation reactions for the naphthalene-containing analog 31 (65%) was once again appreciably higher than that of the quinoline and isoquinoline derivatives 32–36 (31–51%), but there appeared to be no significant

• measurably bioactive, including those serving as controls for the five bioactive derivatives, highlighting the additional importance of structural rigidity on bioactivity within this series. Elucidation of the mechanism of action for these bioactive pentacyclic compounds will be the focus of future

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

• pyrimidine recognition problem with a threefold strategy (Figure 3). First, we aimed to focus primarily on U–A recognition due to the poor selectivity of E [30], the promiscuous behavior of S [31], and the synthetic advantages imparted by commercially available uracil derivatives that could be readily

• nucleobases that showed enhanced triplex stability through cooperative effects compared to the control thymine base. In a follow up study, the pendant amide was removed from the Io core to determine the importance of the third hydrogen bond. To our surprise, these second-generation Io derivatives retained