Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• (Figure S44 in Supporting Information File 1). In vitro carbonic anhydrase inhibition In vitro assessment of all targeted pyrazolobenzothiazine scaffolds for human carbonic anhydrase (hCA) inhibition was performed adopting a stopped-flow CO2 hydration method. The enzyme inhibition assays were carried out

• -diphenyltetrazolium bromide]. Control metabolic activity shown by cells treated with 0.1% DMSO was set to 100% cell growth. CA inhibition assays The inhibition potential of the synthesized compound 7a–h against different hCAs (I, II, IX, XII) was analyzed by adopting a stopped-flow CO2 hydration method described by

• /benzyl/cyclohexyl groups. Experimental data of microbroth dilution assays against different strains of S. aureus.a Experimental data of human carbonic anhydrase (hCAs) inhibition assays adopting a stopped-flow CO2 hydration method. Supporting Information Supporting Information File 6: Experimental

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

• Fitzpatrick et al. [58], allows researchers to oversee chemical reactions online. The hydration of 3-cyanopyridine to an amide was monitored by online MS, offering real-time conversion insights. Through 30 experiments within ten hours, five key reaction parameters were finely tuned for optimal conditions

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• mechanism, as illustrated in Scheme 3b [13][14], we cannot negate this mechanism because the reaction media and bases were different. PCPA 4a was heated in the presence of methanesulfonic acid to undergo 6-endo-dig cyclization. However, hydration predominantly occurred, converting the ethynyl group to a

• phenacyl group, yielding 9 without any detectable cyclization product (Scheme 4). This hydration process is thought to proceed via two paths. The reaction is initiated by the protonation of the ethynyl group to generate the vinyl cation intermediate 10. Product 9 is directly formed by the attack of a water

• through successive nucleophilic additions to the central carbon atom of DEMO. Cyclization of 4a quenched by D2O. Plausible mechanisms for the ring closure of 4. Hydration of the ethynyl group of 4a. Optimization of the reaction conditions for the reaction of 1a with the lithium acetylide of 3a. Addition

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• localized near the surface of phospholipid membranes [11][12]. With this model system, we aimed to examine whether both the intramembrane localization and the photodynamic actions of catC60 can be modulated by PyBA. Results and Discussion The catC60-loaded liposomes (catC60-lip) were prepared by hydration

• the photocontrol of the plasma membrane potential (Vm) using fullerene-containing triad molecules on a millisecond scale. Experimental Preparation of liposomes with catC60 (catC60-lip) or C60 (C60-lip) Liposomes were prepared using a thin-film hydration method. DMPC (NOF AMERICA Corporation, White

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• carbene (NHC) framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts, which demonstrated strong catalytic activity in gold-catalyzed alkyne hydration and arylative cyclization reactions [14]. The synthesis of this new carbene involved the use of a novel nitrenoid reagent that was

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• substances. Host CDs are highly accommodative to water molecules as well and usually contain water in the native state. There is still an ongoing discussion on both the total number of water molecules and their preferred binding position inside the cavities of the CDs. To understand the hydration/dehydration

• light on the mechanism of the γ-CD hydration and to address some unanswered questions: (i) what are the preferable locations for water molecules in the macrocyclic cavity (“hot spots”); (ii) what are the major factors contributing to the stability of the water cluster in the CD interior; (iii) what type

• of interactions (i.e., water–water and/or water–CD walls) contribute to the stability of the water assemble; (iv) how does the mechanism of the γ-CD hydration compare with those of its α-CD and β-CD counterparts. Keywords: cyclodextrin; DFT calculation; DSC/TG; hydration; thermodynamic

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• hydration reaction of carbon dioxide to bicarbonate, cyanates to carbamic acids, aldehydes to gem-diols, etc., and represent a potential therapeutic target for diseases like osteoporosis, edema, obesity or cancer [29]. Alım et al. [30] evaluated a series of thiophene sulfonamides based on the high stability

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• azido-hydration reaction [18]. The homopropargylic azide was obtained in only 28% yield using phenyl vinyl ketone. Based on reported aza-alkynylation reactions [19][20][21][22][23] and modern azidation methods using radical chemistry [17][24][25][26] three approaches could be envisaged. All of them

A laterally-fused N-heterocyclic carbene framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts

• Andrew D. Gillie,
• Matthew G. Wakeling,
• Bethan L. Greene,
• Louise Male and
• Paul W. Davies

Beilstein J. Org. Chem. 2024, 20, 621–627, doi:10.3762/bjoc.20.54

• -step ynamide annulation and imidazolium ring-formation sequence. Metalation with Au(I), Cu(I) and Ir(I) at the C2 position provides an L-shaped NHC ligand scaffold that has been validated in gold-catalysed alkyne hydration and arylative cyclisation reactions. Keywords: annulation; carbene; gold

• ], intramolecular cyclisation [36] or a mixture of both [8][37][38][39]. The new ligand system proved to deliver competent catalysis. Conversion was seen in all cases at 1 mol % catalyst loading (Scheme 3). Use of 13 resulted in a slight increase of the anti-Markovnikov hydration product 17 over 18 when compared to

Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study

• Yasuhiro Oishi,
• Motoharu Kitatani and
• Koichi Kusakabe

Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49

• molecules because the chain portion of PASE turns upward. Therefore, the stabilization energy of hydrogen-bond formation is greater in conformation 2 than in conformation 1. To improve the stability of conformation 2, hydration effects by electrostatic interactions between PASE and the solvent are also

• important. A selective hydration of the polar moiety while keeping the pyrene moiety stable can relatively strengthen the stability of conformation 2. Thus, as the polarity of the solvent increases, the probability of conformation 2 appearance is expected to increase. Mechanism of bi-stability in PASE on

• molecule turns upward, increasing the number of sites that can form hydrogen bonds with water molecules in conformation II. Therefore, the formation of hydrogen bonds can stabilize conformation II relatively more strongly than conformation I. The hydration effect also improves the stability of conformation

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• less than half complete at the transition state [79]. In foundational work on alkene hydration by Evans and Kirby, a general acid-catalyzed mechanism is concluded, and small isotope effects are observed despite H–O bond breaking in the transition state [80]. In an excellent study by Borhan and co

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• , UK Department of Chemistry, Sapienza University of Rome, piazzale Aldo Moro, 5, 00185 Rome, Italy 10.3762/bjoc.19.147 Abstract In order to replace the expensive metal/ligand catalysts and classic toxic and volatile solvents, commonly used for the hydration of alkynes, the hydration reaction of

• costs. The developed method was efficaciously applied to different alkynes, achieving the desired hydration products with good yields. The results obtained using a conventional approach (i.e., adding BF3·Et2O) were compared with those achieved using BF3 electrogenerated in BMIm-BF4, demonstrating the

• possibility of obtaining the products of alkyne hydration with analogous or improved yields, using less hazardous precursors to generate the reactive species in situ. In particular, for terminal arylalkynes, the electrochemical route proved to be advantageous, yielding preferentially the hydration products vs

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• beige and light-yellow solids with 78% and 44% yield, respectively. Thermal analyses between 25 and 350 °C were performed in order to verify the hydration status of the bulk. Regarding hdz-CH3, a weight loss of 9.78% from around 80 to 190 °C was observed, suggesting the presence of two crystallization

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• split over two positions yielding in total 5.75 mol of water per CO2. The hydration is similar to that of native α-CD [13] and that of the krypton inclusion complex which has 5.28 water/Kr [14]. The CO2 molecule refines with an optimal occupancy of 0.84 and linear geometry (178.2(6)o) with C–O bond

• change in spectrum of 7 provided 7 and CO2 compete for the binding site. To avoid problems with formation of hydrogencarbonate the experiments were conducted in a buffer at pH 3 where only a minor fraction of the carbonic acid (pKa1 = 3.6) is dissociated and since the hydration constant of CO2 is small

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• interconvertible to each other by hydration or dehydration, i.e., a plausible precursor of the allylic alcohol would be the diene, and vice versa [90]. Since both 8 and 10 are easily obtainable from 2 by Mozoroki–Heck coupling with commercially available 2-methyl-3-buten-2-ol, ester hydrolysis (LiOH in THF/H2O

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• (toluene, acetonitrile, DMSO-d6) at room temperature, or when these solutions were slightly heated, the compounds 5a,b,e dissociated to form APBTTs 1 (the solutions got violet color, characteristic of compounds 1) (Scheme 10). In the presence of water (including the atmospheric moisture), hydration

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• bicyclic scope was limited as other bicycles such as norbornene failed to react. The authors propose the catalytic cycle begins with the Rh(III)-catalyzed hydration of the alkynol to produce 186 followed by a Sc(III)-catalyzed addition to form the transient hemiketal 187. Ortho-C–H activation generates 188

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• %. The difference in the yield can be explained by the level of hydration, as was determined by TG (see below). For the 1:1:1 complexes, the mass loss is half in comparison with the water content of β-CD (6.4–7.4% for complexes and 14% for β-CD hydrate). On the other hand, the mass loss of the 3:1:1

• complexes is much higher (e.g., 11.8% for X3N complex). As a consequence, the 1:1:1 complexes lose relatively more hydration water than the corresponding 3:1:1 complexes. This can be explained by the high level of complexation for the 1:1:1 complexes. This aspect could be confirmed by thermal analysis

• especially appear for OH, CC and CH/CH2 bonds and groups. However, CD specific bands also appear for CH groups in the CD ring and α-type glycosidic bonds. Thus, a broad FTIR band corresponding to the stretching vibration of the O–H bonds in β-CD and hydration water molecules appears at ≈3301 cm−1. A weak

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• reactions of transition metal hydrides (Fe, Co, Mn, etc) with alkenes (e.g., Mukaiyama hydration) [20]. The last decade saw the development of milder methods for generating carbon-centered radicals as the advancement of their reactivity in cross-coupling reactions, the concept of photoredox catalysis [21

• Mukaiyama hydration [20] to furnish natural complexity. A similar approach was devised for the synthesis of modified meroterpenoids chevalone A (52), taondiol (53), decaturin E (54), and stypodiol (57, Scheme 4). For this purpose, tricycle 45 was prepared from compound 44 in gram-scale quantities by HAT

• (dba)3, SPhos, and Et3N in 86% yield. Reduction of the double bond with Pd/C followed by dual Stille coupling for the introduction of two methyl groups and Mukaiyama hydration utilizing Mn(dpm)3 and PhSiH3 furnished the misassigned structure for dysiherbol A (79). A revised structure was finally

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• technique after a synthetic transformation are highlighted in the following section (Scheme 14, Table 3). A continuous flow crystallization was performed using a trisegmented tubular crystallizer (KRAIC) coupled with a catalytic hydration of pyrazine carbonitrile [115]. After passing the reaction setup, the

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• enone 10 to the corresponding allylic alcohol, followed by a Au-catalyzed alkyne hydration, providing hemiketal 11. This intermediate was in equilibrium with hydroxy-ketone 12, which was suitable for a SmI2-promoted cyclization, affording intermediate 13 selectively, already bearing rings C and D. The

• corresponding ketone was achieved using Dess–Martin periodinane with a pyridine buffer. Addition of Me3SiCH2Li efficiently afforded the Peterson adduct 33. The 1,1-disubtituted alkene was then submitted to Mukaiyma hydration to form the tertiary alcohol, in presence of Mn(dpm)3, PhSiH3 and O2. Then, the ketone

• ketone methylation gave access to 56. Directed C1–C5 vanadium-mediated epoxidation followed by DBU treatment and TBS deprotection afforded 57 in one pot. The tertiary alcohol 58 was obtained as a single diastereomer after hydration of position C18. Subsequent reduction with DIBAL-H gave the desired

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• titration of a DMSO to a DMSO with 5 vol % of water was carried out to manifest the contamination with water (see Supporting Information File 1). Therefore, the exothermic signal from the dilution of CDs in DMSO was attributed to the hydration of hydroxy and, to a lesser extent, methoxy groups from

Molecular diversity of the base-promoted reaction of phenacylmalononitriles with dialkyl but-2-ynedioates

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

Beilstein J. Org. Chem. 2022, 18, 991–998, doi:10.3762/bjoc.18.99

• produced a bridged cyclic 2-oxabicyclo[2.2.1]hept-5-ene D. The further hydration of intermediate D gave intermediate E, which was in turn transferred to cyclopentenyl intermediate F by the ring opening of the bridge ring. In the cyclopentenyl intermediate F, the hydroxy group and the amide group clearly

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• amine) on the most electrophilic component of the α-ketoaldehyde (its aldehyde) to give intermediate 5. However, the ensuing cyclization (via a hydration of its imine bond to allow for a rotation) would then lead to compound 4 which is rarely the major reaction product. Since compound 3 is the main

Cs₂CO₃-Promoted reaction of tertiary bromopropargylic alcohols and phenols in DMF: a novel approach to α-phenoxyketones

• Ol'ga G. Volostnykh,
• Olesya A. Shemyakina,
• Anton V. Stepanov and
• Igor' A. Ushakov

Beilstein J. Org. Chem. 2022, 18, 420–428, doi:10.3762/bjoc.18.44

• highly selective hydration/acylation of tertiary bromopropargylic alcohols with carboxylic acids promoted by alkali metal carbonates [24]. The reaction proceeds via the ring-opening of 1,3-dioxolan-2-one intermediates formed with hydroxy and alkynyl groups of bromopropargylic alcohol and alkali metal

• in 6–9% preparative yield. Hydrocarbonates CsHCO3 and KHCO3 were also tested in the reaction, which gave 5-bromomethylene-1,3-dioxolan-2-one 6a as a major product in 29–36% yield (Table 1, entries 11 and 12). Considering that hydration occurs during the formation of phenoxyketone 4a, we added water

• formation of phenoxyhydroxyketone 4 proceeds via 1,3-dioxolan-2-one 6 generated from bromopropargylic alcohol 1 and Cs2CO3. Then, Br-substitution/hydration of 6 and the release of CO2 give product 4 (Scheme 7). Apparently, diphenoxyketone 5 results from decarboxylative conversion of 1,3-dioxolan-2-one 7