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

• with an electrophilic handle for the covalent attachment of the surrogate to the RNA. The resulting irreversibly tethered dye–RNA complexes have opened up new avenues for RNA imaging in live cells. Here, we report the syntheses of such modified HBC530 ((4-((2-hydroxyethyl)(methyl)amino)benzylidene

• 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

• and the new ones) for covalent attachment to the Pepper aptamer in vitro. Results and Discussion Background The fluorescent light-up aptamer Pepper binds a series of structurally related synthetic dyes that contain a stilbene core. The lead compound is (4-((2-hydroxyethyl)(methyl)amino)benzylidene

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

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• was observed. Conclusion A method for the synthesis of new push–pull stilbazoles of the type D–π–A was developed. The obtained compounds represent a rare class of benzylidene derivatives of 1-pyrindane. They were characterized by an unusual type of photoluminescence in two states (dual-state emission

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• -galactose and subsequent perbenzoylation afforded an anomeric mixture (α:β = 87:13) of tribenzoyl-4,6-benzylidene-ᴅ-galactose from which the pure α-anomer 10a was separated (Scheme 6) [20]. Cleavage of the acetal and subsequent regioselective replacement of the hydroxy group OH-6 with an iodide by

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• , it is worth mentioning the work of Li and co-workers (2011) [20], who described a single example of the formation of such structures by carrying out an organocatalytic domino aza-Michael–Mannich reaction between benzylidene-1H-imidazol-2-amine and cinnamaldehyde. Although the imidazo[1,2-a

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• presence of carbon dioxide to give the corresponding phenylacetic acids [12]. We found that alkyl benzyl carbonates and benzal diacetates (benzylidene diacetates) were also applicable to electrochemical carboxylation with C(sp3)–O bond cleavage at the benzylic position, yielding phenylacetic acids [13] and

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• low conversions and stereoselectivities when applied to benzylidene acetones or cyclic enones (vide infra). In our latest research in establishing a mild organocatalytic protocol for incorporating benzyl malonates and bisthiomalonates into cyclic enones and benzylidene acetones, we have developed a

• the ideal tool in addition to reactions to cyclic enones and benzylidene acetones. However, our concern was whether the thioester group, whose activity towards nitrogen nucleophiles significantly exceeds that of analogous oxo-esters [26][27][40], would remain unaffected in the presence of a

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• 1H NMR spectroscopy data, one of its components was the product of the migration of the double bond of the benzylidene fragment into the succinimide cycle – compound 22. Finally, a compound with a longer side chain 24, obtained from 2-(2-bromoethoxy)ethanol (23), underwent exclusively isomerization

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• using established procedures from the literature, commencing with ᴅ-glucosamine and benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-ᴅ-glucopyranoside as the starting materials, respectively [40][41][42][43]. Imidate donors 1a and 1e were obtained exclusively as α-anomers, and 1b and 1g as a 1:1 α:β

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• , taking care not to affect the Troc group, to afford acceptor 5 in a 96% yield. Earlier optimizations of the introduction of the β-linked galactose moiety using 2-azidoethyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-ᴅ-galactopyranoside as acceptor showed an acetylated thioglycoside donor to be the best

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• scaffolds is the introduction of a benzylidene moiety on C5 via a Knoevenagel reaction. Here, a facile synthesis of 5-arylidenerhodanines via a Knoevenagel reaction in an ʟ-proline-based deep eutectic solvent (DES) is reported. This method is fast (1 h at 60 °C), easy, catalyst-free and sustainable as no

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• 24.5. In addition to the stereocontrolled synthesis of AMG reported in Figure 21 [116] and Figure 22 [118], another possibility uses dimethyl-ᴅ-tartrate (25.1) as chiral precursor (Figure 25) [81]. This 8-step synthesis starts with the protection of the diol to form the benzylidene tartrate 25.2. Then

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• crystallography. In all other cases, only the pure syn diastereomer was isolated and characterized. The yields of spirocyclic products were generally modest to good over two steps. An electron-accepting group in the benzylidene portion (5j) or an N-benzyl substitution in the starting material (5g) lowered the

Radical cation Diels–Alder reactions of arylidene cycloalkanes

• Kaii Nakayama,
• Hidehiro Kamiya and
• Yohei Okada

Beilstein J. Org. Chem. 2022, 18, 1100–1106, doi:10.3762/bjoc.18.112

• benzylidene cycloalkanes and therefore, the results described herein may support a detailed mechanistic understanding. Further experimental and theoretical studies of radical cation cycloadditions of arylidene cycloalkanes are under investigation in our laboratory. Experimental Photoelectrochemical: The

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• should be pointed out that the exocyclic benzylidene group exists on the C3-position in the newly formed cyclohexyl ring, while it exists on the C6-position in the above obtained spiro compounds 3a–z. This result clearly indicated that these two reactions have the opposite regioselectivity. Another kind

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

• other hand, their specific geometry enables intriguing transformations with simultaneous involvement of the diazo function and the benzylidene fragment. DAS were first described in 2020 and were involved in a [2 + 1] cycloaddition to aldehydes to give oxiranes [1]. Later on, we developed a convenient

• benzylidene fragment (1g) led to the deactivation of the diazo substrate ‒ after 1 hour the conversion did not exceed 30% and even after 3 days the starting DAS 1g was still present in the mixture. At the same time, only a trace amount of the expected dimerization product 2g was detected along unidentified

• ortho-methyl substituent in the benzylidene fragment. In this case, along with conventional reaction products ‒ dimer 2r and indene 3r, unexpectedly the cyclobutane 5, a product of the formal [2 + 2] cycloaddition, was isolated in low yield (Scheme 1); its structure was confirmed by single-crystal X-ray

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• catalyst for the oxidation of 2-methylnaphthalene (16) with H2O2 [59]. The complex L1-Fe(III) (L1 = (2-((2-(2-((2-((2-hydroxyphenylimino)methyl)phenoxy)methyl)benzyloxy)benzylidene)amino)phenol) showed the best catalytic activity with 58.54% selectivity and 79.11% conversion (Table 1, entry 13) [59

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• to synthesise indoloquinolizidines [5]. Moreover, six-membered and five-membered cyclic 1,3-diketones have been investigated in reactions with acetates of nitroalkenes [6], cyanoacrylates and benzylidene malononitriles [7], ortho-hydroxy-benzhydryl alcohols [8], α,β-unsaturated pyrazolamides [9] and

• in carbohydrate chemistry [15]. Cyclic six-membered 1,2-diketones have been shown to react with benzylidene malononitriles [7][16], β-nitrostyrenes [17] and substituted propionaldehydes [18]. For a while, there were no examples related to cyclopentane-1,2-dione (CPD). In 2004, the first instance of

• thiourea catalysts were screened in a model reaction between CPD 1 and Boc-protected benzylidene oxindole 2a at room temperature in the presence of 10 mol % of catalyst (Figure 2). First, the quinidine-derived squaramide A was used and the desired product was obtained as a mixture of chromatographically

Total synthesis of the O-antigen repeating unit of Providencia stuartii O49 serotype through linear and one-pot assemblies

• Tanmoy Halder and
• Somnath Yadav

Beilstein J. Org. Chem. 2021, 17, 2915–2921, doi:10.3762/bjoc.17.199

• on the hydroxy groups. First, the concomitant removal of the Troc group and the N-acetylation was achieved using Zn/AcOH/Ac2O 3:2:1 as reagent in one pot (Scheme 6) [52]. Then, O-deacetylation was accomplished by using a catalytic amount of NaOMe in MeOH at room temperature. Finally, the benzylidene

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• arrangement would facilitate the intramolecular Friedel–Crafts cyclization of the MBH adducts. Cycloaddition of azomethine imine 7a with 2-substituted-1H-indenes 6b and 6c was attempted to ascertain the structure of the synthesized 1H-indenes (Scheme 3). The azomethine imine, 1-benzylidene-3-oxopyrazolidin-1

• ; found, 174.0706 Synthesis of 1-benzylidene-3-oxopyrazolidin-1-ium-2-ide (7a) A methyl acrylate (0.0225 mol) solution was added drop-wise to the solution of hydrazine monohydrate (0.0205 mol) in 20 mL of ethanol. This solution was stirred at 78 °C for 4 hours; the solvent was evaporated and the residue

• (6C, aro-C), 57.92 (1C, N-CH2), 29.38 (1C, CO-CH2); HRMS (m/z): [M + H]+ calcd for C10H10N2O, 174.0793; found, 174.0818. Typical procedure for synthesis of compounds 8a and 8b Indene 6b (1 mmol) in 2 mL of toluene was successively added to 1-benzylidene-3-oxopyrazolidin-1-ium-2-ide (1.2 mmol). The

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• dramatic when 2,4-di-O-acyl groups are present, sometimes leading to exclusive formation of α-anomers [128][129]. PGs like 2-O-ADMB (4-acetoxy-2,2-dimethylbutanoate) [130] or 2,2’-O-benzylidene [131] were introduced to solve this issue. Several reports highlighted the importance of the 4,6-O-benzylidene

• group on the glycosyl donor and the acceptor for the stereoselective formation of the β(1–3) linkage (Figure 4) [132]. Interestingly, oligomers bearing several 4,6-O-benzylidene groups show anomalously small coupling constants for some of the C-1 hydrogens. NMR [133] and X-ray [134] studies revealed

• that, for some residues, the 4,6-O-benzylidene group stabilizes a boat conformation (1,4B or B2,5), in contrast to the standard chair (4C1). This unexpected conformation did not affect the stereoselectivity of the glycosylation, permitting the preparation of linear β(1–3)-glucans of different lengths

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• column chromatography on silica gel (petroleum/EtOAc 5:1 to 2:1, with 1% Et3N), yielding the desired product 3. (Z)-3-Benzylidene-2-(methyl[pyridin-2-yl]amino)isoindolin-1-one (3aa) The general procedure was followed using hydrazide 1a (68.2 mg, 0.30 mmol) and alkyne 2a (91.9 mg, 0.90 mmol). Purification

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• ). Finally, nitroketone 2n with a cyclohexyl group was engaged in the reaction and a moderate enantioselectivity was detected for product 3n (Table 2, entry 14). In the next step, we investigated the scope of the reaction of substrate 2a with a variety of pyrrolidine-2,3-diones 1 having different benzylidene

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• ). 4,6-O-Benzylidenation of diol 18 followed by regioselective opening of the benzylidene acetal produced compound 35. Subsequent DAST deoxyfluorination delivered the desired thioglycoside 36 (Scheme 3). For both compounds 18 and 35, deoxyfluorination of the C4 hydroxy group occurred with inversion of

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• achieved from other starting materials, such as 2-methyl-6-(phenylethynyl)pyridine [36], 2,6-dimethylpyridine (1a) and (E)-N-benzylidene-4-methylbenzenesulfonamide [22], 2-bromo-6-methylpyridine and (E)-styrylboronic acid [37], as well as 2-methylpyridine and phenylmethanamine [38]. Most recently