Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• aglycone sarmentogenin in 7 steps from 17-deoxycortisone. The synthesis features a scalable enzymatic C14–H α-hydroxylation, a Bestmann ylide-enabled one-step construction of the butenolide motif, a late stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction. Keywords: cardiac glycosides

• ; C–H hydroxylation; chemoenzymatic synthesis; Mukaiyama hydration; protecting-group-free synthesis; Introduction Cardiac glycosides (CGs) are widely distributed natural products, generated by plants and amphibians [1]. Structurally, they are composed of an aglycone-steroidal moiety, an unsaturated

• donor, through a late-stage glycosylation. The aglycon 2 can be derived from the Δ14 olefin intermediate 3 via Mukaiyama hydration and several functional group transformations. In turn, 3 would be generated from the key C14α-hydroxylated intermediate 4 via an elimination process. For the synthesis of 4

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

• remains a major challenge due to the strong hydration of anions. Here, we report the preparation of silica gel functionalized with covalently anchored bambusuril macrocycles. In aqueous solution, this material efficiently sorbs dicyanoaurate(I), the key anion in gold mining, even in the presence of

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• reductive Heck reaction of 59 enabled the transannular connection between C4 and C5, generating key intermediate 60, which possesses the same carbon skeleton as the proposed biosynthetic key intermediate 50 and contains the suitable functional groups for further elaboration. Mukaiyama hydration of 60

• ]dec-5-ene)-catalyzed intramolecular aldol reaction connected C6 and C8, assembling the trans-pentalene ring and affording the core carbon framework of illisimonin A. The C1 hydroxy group was initially introduced by a Mukaiyama hydration reaction using O2 as the stoichiometric oxidant; however

• -catalyzed oxidative lactonization, yielding 76 with a newly established quaternary center at C1 and isomerization of the double bond to C2=C3. Photocatalyzed isomerization of the C2–C3 double bond in 76 to C3=C4 furnished 77 [39][40]. A Mukaiyama hydration introduced a hydroxy group at C4, accompanied by

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

• follows: Commercially available compounds 31 and 32 were converted to the C2-symmetric 33 over 13 steps, enabling construction of the AB bicyclic skeleton in the target molecules. Compound 33 then underwent Mukaiyama hydration to adjust the C15 oxidation state, followed by water-promoted consecutive

• successfully accomplished via an epoxide ring-opening/tandem lactonization/olefin hydration sequence. In total, 12 consecutive redox manipulations (7 oxidations and 5 reductions) established all stereocenters, with subsequent functional group transformations completing the total synthesis of garajonone (8

• transesterification sequence produced mono-enone 106, whose hydration installed the C6 stereocenter to yield 107. Further protecting group and oxidation state adjustments afforded lactone 108, which was transformed via an intramolecular SN2′ reaction (single-electron reduction), m-CPBA epoxidation, acid-promoted

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• structure, and saturation, can result in different membrane mechanics, hydration, thickness, intermolecular spacing, and non-covalent interactions with the rotaxane. For example, EYPC bilayer thickness increases linearly with cholesterol concentration and can induce the formation of nanodomains [16]. Such

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• bonds of 83 (Scheme 10). Building block 76 was first obtained in 18% overall yield from β-ketoester 74 through a sequence involving Michael addition, decarboxylation, nitrile hydration, and cyclization under vacuum. Aminoketal 81 – a direct precursor to the oxygen-sensitive α,β-unsaturated iminium 81a

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

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• underwent the 1,2-addition of isopropenyllithium reagent (prepared from n-BuLi/tetraisopropenyltin (67) [55]) and DMP oxidation to afford ketone 68. A three-step transformation including RCM, Mukaiyama hydration, and esterification, 68 was converted to methyl oxalate 69. Irradiation of the reaction mixture

• transformations of 121 generated bromodiene 122. Next, the metal–halogen exchange/intermolecular addition of 122 with aldehyde (+)-123 and in situ PtCl2-promoted hydrolysis and hydration gave tricyclic product 124. The BnMe3NOH-mediated intramolecular Michael/aldol cascade reaction of 124 constructed the C/D

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• -inflammatory [21][22] as well as enzyme inhibition activities [23][24][25][26]. Traditionally, β-ketophosphonates were prepared via Arbuzov reaction [27], acylation of alkylphosphonates [28], and hydration of alkynylphosphonates [29][30][31]. However, these methods have several drawbacks, including low atom

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• multimetal-organic framework (M-MOF, M= Cu, Ni) which successfully catalyzed the one-pot cyclopropenone hydration/Chan–Lam coupling reaction of 309 and boronic acid 341 to give the corresponding ester 310 in good yield via the formation of acid 342 (Scheme 76B). Cyclopropenone was also subjected to non-metal

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• quaternary center in a single step. As depicted in Scheme 1, key enamide 1 was prepared from (R)-pulegone in 6 steps. In the presence of the weak acid H3PO4, protonation of 1 generates a stabilized iminium ion 2, which then undergoes a 6-exo-trig cyclization to deliver 4 after hydration of cation 3. Notably

• the reduction of amide-generated ketone 12 after a subsequent Dess–Martin oxidation. Upon treatment of 12 with Co(acac)2 and PhSiH3 in iPrOH at 80 °C, the Mukaiyama hydration of enamide delivered hemiaminal 13. Despite the incorrect configuration of the newly formed hydroxy group, it is considered

• inconsequential due to the reversibility of hemiaminal. Consequently, further reduction of the amide could complete the total synthesis of (+)-fawcettimine with in situ adjustment of the hemiaminal configuration. The incorrect configuration observed in the Mukaiyama hydration also inspired the authors to develop

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• , the extraction efficiency follows the order of PO43− > CO32− > SO42− > NO3−, consistent with the order of negative charges as well as the anions’ hydration energies (Table 1) [49][50]. This anti-Hofmeister selectivity of phosphate over other studied oxyanions is normally seen in liquid–liquid and

• displays higher hydration energy than that of sulfate, and the tetrahedral shape of sulfate anion matches the pseudo-tetrahedral cavity of the folded hexaurea receptor [30]. Secondly, for Cs+ cations, two types of Cs+ binding are shown in the solid state. Two type-(I) cesium cations are found to be

• conteranion, chloride, nitrate, carbonate, sulfate and phosphate) into chloroform, we demonstrate efficient extraction of Cs3PO4 solids. The extraction efficiency follows the order of Cs3PO4 > CsCl > Cs2CO3 > Cs2SO4 > CsNO3, reflecting the hydration energies and binding affinities of the corresponding anions

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