Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• . Nucleophilic substitution of the nitro group with sulfur nucleophiles, including thioacetate or disulfide anions as well as thioacetamide, yielded bis(thiophen-3-yl)disulfide and sulfide derivatives. The disulfide served as a suitable precursor for the preparation of 3-alkylthio-substituted thiophene-2,5

• functionalized thieno[3,2-b]thiophenes with potential applications in pharmaceutical and materials chemistry. Keywords: aromatic nucleophilic substitution; disulfide derivative; 3-nitrothiophene; organic disulfides; thieno[3,2-b]thiophene; thiophene ring closure; Introduction Thieno[3,2-b]thiophene (TT

• . Compound 2 was identified as a bis(thiophen-3-yl)sulfide derivative and compound 3 as a bis(thiophen-3-yl)disulfide derivative, both with methoxycarbonyl groups at the C-2 and C-5 positions of each thiophene ring (Scheme 4). The formation of these unexpected products, sulfide 2 and disulfide 3

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• photodynamic therapy (PDT) capabilities. This system was based on the host–guest interactions between polyethylene glycol-functionalized pillar[5]arene (PEG-P[5]A) and a pyridinium-capped porphyrin derivative containing a disulfide bond (TPPC6-SS-Py). The supramolecular amphiphile could self-assemble into

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• donors of gluco-, galacto-, and manno-configuration, using a sulfonium-type promoter generated in situ from dimethyl disulfide (Me2S2) and triflic anhydride (Tf2O) [66][70]. The use of common acid scavengers, such as DTBP (di-tert-butylmethylpyridine), was not recommended, as glycosylation reactions

• dimethyl disulfide/triflic anhydride and use thioglycosyl donors, 4-O-picoloyl-protected 1-O-TMS-lactol acceptors have been shown to exhibit enhanced β-stereoselectivity, likely due to the formation of a transient picolinium adduct with the TMS-glycoside. Tribenzylated 4-O-picoloyl-1-O-TMS-β-glycoside 101

• acceptor 153, using a sulfonium-type promoter prepared from dimethyl disulfide and triflic anhydride, produced the α,α-1,1'-linked diglucoside 154 (Scheme 13) [121]. Similarly, partially desymmetrized trehalose derivatives 157 and 159 were prepared using 2-O-picoloyl 3-O-Nap- and 3,6-di-O-Nap-protected TMS

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

• ΔEST of order 10−7 kcal mol−1 (see Figure 12a) [98]. No photoluminescence has been reported for bPTM; however, this diradical shows extremely long coherence times of order T1 = 1 s (thermalization, spin lattice relaxation) and TM ≈ 67 µs (phase memory time), both determined in carbon disulfide as a

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• typically more evenly distributed in antibodies than lysine but are often tied up in disulfide bridges that must be reduced prior to conjugation [24][25]. Such reductions must thus be carefully controlled to allow conjugation while ensuring the overall structural integrity of the antibody. The free

• method allows the same photocatalyst and electrophile to be involved in two different but selective bioconjugations of mAbs. It remains limited to reactions involving oxidative mechanistic pathways with 1O2. Cys In 2016, Bräse et al. developed a photomediated disulfide rebridging method, exploiting the

• disulfide bridging sites in biomolecules to introduce specific functional groups (Figure 6) [44]. The bioconjugation reaction is based on thiol–yne coupling. Originally developed on peptides and proteins, this approach was applied to a fragment antigen-binding (Fab) antibody fragment (approximately 46 kDa

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• conversion of the thioether-containing methionine to hydantoin (H2j) was obtained with a moderate yield of 59%. Lastly, no hydantoin product was observed by 1H NMR when cysteine was subject to the one-pot procedure, possibly due to disulfide formation of the highly nucleophilic thiol group of the cysteine

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• %), but when DMSO is used as solvent and reagent, the yield was greatly improved. The proposed mechanism involves the activation of the disulfide component by CuBr2 as the Lewis acid (Scheme 14). The copper(II) center coordinates the sulfur atom of the disulfide allowing for the electrophilic addition to

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• groups in organic synthesis [1][2][3][4]. In chemistry and biology, disulfide bonds play crucial roles in protein folding and stabilization [5][6][7][8] and in the rubber industry, they are used to link different polymer chains [9][10]. The disulfide bond backbone is commonly used as a linker for

• antibody–drug coupling (ADCs), in which the active drug released in the target cell by selectively breaking the disulfide bond [11]. Given the wide applicability of disulfides, the development of efficient, green, mild, and cost-effective methods for the organic synthesis of disulfides is of significant

• importance. In the field of disulfide synthesis, the conventional approach mainly involves oxidizing thiols to form disulfides. This process employs various oxidation agents, which can be categorized as nonmetallic and metal derivatives [12][13][14][15][16]. Over the past few years, the implementation of

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• . A deeper analysis of the composition of the crude mixture revealed the presence of sulfide 3a and disulfide 7a, which formation might probably result from an oxidative reaction involving species generated from 2 sulfenate molecules. A further experiment was carried out in the absence of light. Under

• reactions could undergo disproportionation, a radical process resulting in the homolytic cleavage of the S–O bond [35]. The formation of disulfide 7 isolated in the experiments can be explained by combining two radical sulfur species. Furthermore, the oxygen species generated in this radical reaction may

• : 4a (2 equiv), NaH (2.4 equiv), 2a, TEMPO (10 mol %), degassed DMF (0.055 M). NO – not observed. Mechanism proposed for sulfonamide 5, β-sulfinyl ester 4, disulfide 7, and sulfide 3 formations. The ionic steps are illustrated in green, whereas the radical steps appear in purple [35]. Optimization of

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

• intermediate C which underwent extrusion of iodine and dipropyl disulfide to give intermediate D. Subsequent reaction with acetic anhydride, pyridine and KHF2 resulted in the replacement of the TMS by acetyl groups which was important for practical reasons (stability during chromatography). The reaction of 13

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

• branch could not be determined due to the decreasing peak intensity with increasing fragment chain length. To determine the position of the double bond position, we performed a microderivatization with dimethyl disulfide (DMDS) of a methylated extract. Unfortunately, we were unable to detect the

• room temperature for 1 h. The solvent was removed with a stream of N2 and the sample was taken up in CH2Cl2 and analyzed by GC–MS [43]. Dimethyl disulfide derivatization: Twenty µL of the sample in a 2 mL GC vial were diluted with pentane (20 µL) and mixed with freshly distilled dimethyl disulfide

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• atomoxetine, metaxalone, and tadalafil. Mechanistically, thiophenol is oxidized at the anode to the corresponding radical by SET, then dimerizes into a disulfide, which is further oxidized into an intermediate cation radical, yielding a highly electrophilic species. Subsequently, a selective anisole attack

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• mechanism. In the case of tertiary alkanethiols and arylmethanethiols, the corresponding imidoyl radicals 2 decompose to give tertiary alkyl and benzylic radicals, respectively, to form isothiocyanates 5. On the other hand, we have investigated the radical addition of diphenyl disulfide to isocyanides under

• photoirradiation. The photoinduced radical addition of the disulfide to aliphatic isocyanides hardly proceeds, whereas the radical addition to aromatic isocyanides proceeds under high concentration conditions using excess amounts of (PhS)2, selectively yielding 1,1-addition product 4 (R = 2,6-xylyl, E = PhS) [28

• (kSe = 1.2 × 107 M−1s−1) is known to be ca. 160 times higher than that of (PhS)2 [31]. Therefore, we investigated the radical addition to isocyanides using a disulfide–diselenide binary system under photoirradiation and found that the thioselenation of aromatic isocyanides proceeded efficiently to

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• the selected force field is required before running MD simulations. Other modifications can include adding a disulfide bond between specific cysteines and filling the missing side chains and missing loops (if any) to restore the integrity of the protein. Here, we list a series of software tools and

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• significant topic. Surprisingly, there has been limited information on 5-deazaalloxazines (dAll) synthesis [20][21][22]. Most known methods employ the cyclization of 6-(arylamino)uracils with one-carbon reagents such as triethyl orthoformate, dimethylformamide dimethylacetal, carbon disulfide, N,N

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• activity of nisin, a lanthipeptide produced by certain strains of Lactococcus lactis, is dependent on thioether-ring formation [14]. Additional post-translational modifications contributing to their distinct biological activities were identified [15][16]. Intermolecular disulfide bridges were proved to

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

• stability by introduction of disulfide bonds [112][113]. Two new alginate lyases, AlgL17 and AlgL6, both expressed in E. coli, were characterized from Microbulbifer sp. ALW1 isolated from rotten brown algae [61][62]. AlgL17 preferentially degraded polyM with poor activity towards polyG, indicating it to be

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

•  21). Styrenes selectively reacted with vinyl ethers in the presence of an acridinium photocatalyst and a diphenyl disulfide HAT catalyst to produce the aldehyde product when exposed to blue LED light. Differently substituted styrenes were examined using this protocol, which produced the aldehyde

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

• results were not fully satisfactory. Considering the poor solubility of fullerene derivatives, toluene, carbon disulfide (CS2), and ortho-dichlorobenzene (o-DCB) were tested as solvent. Surprisingly, the conversion from ketone to thioketone did not occur as anticipated. In another attempt, where the

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• ). Whilst tetrabutylammonium borohydride [22] at room temperature did not lead to a conversion of the starting material 5 either, a trace amount of desired 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine 7b was formed at elevated temperature, accompanied by disulfide 18b as the main product (Table 1, entries 5 and

• ]pyridine 7b was formed together with disulfide 18b and aminoborane 17b (Table 1, entry 11). We thus evaluated B(C6F5)3 as a nonmetallic catalyst to activate ammonia borane in the reductive hydrogenation of the C=N-bond in [1,3]thiazolo[4,5-b]pyridines 5 and 15c. In line with reports on the hydrogenation of

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• C60 and C70 complexation, with selectivity for C70 (log KC60 = 3.3 and log KC70 = 4.7). In a follow-up of this work, they reported a similar redox-switchable biscorannulene tweezers system with a bis(arylthiol) switching unit that can be locked in the cis-conformation by forming a disulfide S–S bridge

• preferred conformation. It was achieved in tweezers 42 by the formation of an intramolecular disulfide bridge, that enables non-covalent bonds with aromatic moieties and results in a favored syn-conformation (Figure 23a) [89]. Yet, the most explored way is to use an electroactive moiety that can change its

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• in bacteria as well as the oxidative environment of the secretory pathway, as CMA1 exhibits predicted disulfide bridges. A single step of His-tag affinity chromatography was sufficient to yield protein of adequate purity and good yield (≈15 mg of eluted protein from 800 mL of cell culture, Figure 1c

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• ]. Similarly to the early transformations of thiepines, sulfur elimination was triggered by copper bronze at high temperature, thus leading to the conversion of the 6-membered cyclic disulfide into the corresponding thiophene. The 1,2-dithiin scaffold is found in natural products such as thiarubrines A and B

• , along with the 5-membered 1,8-naphthalene disulfide 49 resulting from the ring contraction of precursor 47. Such SO transfer process, favoured by the peri-interaction existing in the trisulfide-2-oxide substrate, was also successfully promoted by light and the cyclic sulfoxide 50 was obtained under

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• cyclic (alkyl)(amino) or mesoionic carbenes (CAACs or MICs) onto carbon disulfide. Nine novel compounds were isolated and fully characterized by 1H and 13C NMR, FTIR, and HRMS techniques. Moreover, the molecular structures of two CAAC·CS2 and two MIC·CS2 betaines were determined by X-ray diffraction

• applications [24][25][26][27][28]. N-Heterocyclic carbenes and their enetetramine dimers readily add to the central carbon atom of allenes and heteroallenes X=C=Y (X, Y = CR2, NR, O, S) to afford zwitterionic adducts [29]. In particular, their reaction with carbon disulfide affords stable azolium-2

• (−)-menthone was obtained in a separate step by deprotonating the corresponding aldiminium triflate with lithium diisopropylamide (LDA) at −78 °C [8]. Herein, we disclose the synthesis of three CAAC·CS2 and six MIC·CS2 inner salts from the corresponding aldiminium or 1,2,3-triazolium salts and carbon disulfide