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

• chains were tethered to the calixarene hydroxy groups (lower rim) by reaction with dodecyl iodide in the presence of NaH. At the upper rim of this derivative, four formyl groups were introduced by reaction with hexamethylenetetramine in trifluoroacetic acid. The formyl groups were reduced to alcohol

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

• , but it was obtained as a mixture of ester forms, namely dimethyl and diethyl esters in ethanol, and dimethyl and diisopropyl esters in isopropanol. These results indicate that the reaction with alcohol solvents resulted in partial transesterification of the methoxycarbonyl groups, while reductive

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• available (+)-sclareolide (101) as starting compound, from which key alcohol 102 was synthesized in 7 steps. Selective mesylation of the secondary alcohol in 102 followed by semipinacol rearrangement catalyzed by t-BuOK afforded diketone 104 as a pair of epimers at C12 in a 1:1 ratio, with 70% overall yield

• reagent 118 using trifluoromethanesulfonic acid (TfOH) or TMSOTf as Lewis acids. The authors suggested that the reaction proceeded via the formation of an intermediate 119 followed by reaction with an alcohol nucleophile and a 1,2-carbon migration to produce a cyclopentane derivative 120 with a yield of

• challenging [6-5-5-7]-tetracyclic ring system embedded within a fully functionalized cyclopentane, as well as seven contiguous stereogenic centers. In 2017, (−)-pavidolide B (134) was prepared in 13 steps from the known chiral alcohol 135, which in turn was synthesized from commercially available (+)-carvone

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• 1,3-dipole and/or dipolarophile and therefore, in some cases, cis-diastereoselectivity arises [85][114][115][116][117]. For instance, in the [3 + 2] cycloaddition reactions examined in earlier studies, intramolecular H-bonding, facilitated by the amide or alcohol functionality present in the nitrone

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• , followed by acetylation of the resulting propargylic alcohol afforded 17 which was further advanced to 18 via copper-catalyzed selective displacement of the propargyl acetate with benzylamine and hydrolysis of the primary acetate. The primary alcohol of 18 was activated with PPh3/CCl4, triggering an

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

• known two-step sequence to 61, followed by Mitsunobu reaction, ester reduction, thioether oxidation, and silylation of the primary alcohol to furnish sulfone 64. The two key fragments – aldehyde 60 and sulfone 64 – were merged via Julia–Kocienski olefination to construct alkene 65. Treatment of 65 with

• (C6F5)3B triggered a Meinwald rearrangement, generating aldehyde 66. Nucleophilic addition, oxidation of the resulting alcohol, and base-promoted epimerization at C6 of 67' delivered 67. Subsequent dihydroxylation of the alkene in 67 and protection of the resulting 1,2-diol as a cyclic carbonate

• , ketone reduction, hydroquinone oxidation, and alcohol oxidation – led to the labile ketone 118. Completion of preussomerin EG3 (99) from 118 relied on a simple sequence including a formal intramolecular 1,6-addition, followed by simultaneous methanol trapping of the resulting electrophilic quinone

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• preferentially initiated 6-endo-trig cyclization, affording iodinated homoallylic alcohol piperidines 15 (Scheme 4, path a). Conversely, cyclopropane-annulated pyrrolidines 17 were constructed using methanol as solvent through hydroxyl radical-mediated 5-exo-trig cyclization pathway (Scheme 4, path b). This

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• investigated. First, alcohol 3 was converted to (R)-MTPA ester 4 (Scheme 1B). Despite numerous attempts to optimize the chromatographic conditions, the resulting diastereomers could not be separated (Figure S1, Supporting Information File 1). Next, p-bromobenzoyl ester 5 was synthesized (Scheme 1B). Although

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• water (5 mL) was added. The mixture was extracted with EtOAc (3 × 5 mL), washed with water (5 mL) and brine (5 mL), dried over MgSO4 and evaporated to give crude products 3 or 10, which were purified by recrystallization from isopropyl alcohol or by flash chromatography. Method B for the preparation of

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• copper catalyst was still required in that procedure. In 2023, Bera presented an electrochemical oxidative [3 + 2] cycloaddition of secondary propargyl alcohol to access 1,2,3-triazole (Scheme 19) [273]. After probing the reaction systematically, the optimal conditions were presented as following: a

• mixture of propargyl alcohol 50 (0.7 mmol), NaN3 (2.8 mmol), n-Bu4NI (0.5 mmol) and MeCN (10 mL) under electrolysis (graphite rod as anode, stainless-steel plate as cathode, 11 mA) at rt for 10 h. According to the experimental results and density functional theory (DFT) calculations, a plausible mechanism

• electrochemical annulation of alkynes with enamides. Electrochemical [3 + 2] cyclization of heteroarylamine was an efficient access towards imidazopyridine. The electrochemical oxidative [3 + 2] cycloaddition of secondary propargyl alcohol produced 1,2,3-triazole. In most of these above reactions, the target

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

• electrocatalyst supported on nitrogen-doped carbon nanosheets (Cu/NCNSs). This catalyst exhibits high activity for the oxidation of various substrates, including GLY, gluconic acid (GLU), 5-hydroxymethylfurfural (HMF), benzyl alcohol (BA), furfuryl alcohol (FA), and ethylene glycol (EG) (Scheme 7) [35]. Park et

• hydrogenation to produce furfuryl alcohol. This latter is a versatile intermediate for the production of resins, coatings, polymers and used as a solvent. It can also be converted into other chemicals through oxidative cleavage, over-reduction and etherification (Scheme 49) [177]. Zhang et al. reported the use

• Meerwein–Ponndorf–Verley reduction, while acetaldehyde is generated in situ by ethanol oxidation (Scheme 50). The equilibrium allows furfural to be simultaneously converted into furfuryl alcohol and 3-(2-furyl)acrolein in one pot through a redox reaction. The highest mass conversion rate of furfural can

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

• reduction of diketone 28 for preparing alcohol 30 under the CBS conditions [8] with (S)-29 as the catalyst (Scheme 1) [14]. Notably, this reaction could be performed on multiple gram scales with satisfactory yield (72%) and ee value (92%). Protection of the alcohol group in 30 with TBSCl followed by

• modification of the terminal double bond afforded ketoaldehyde 31. The 2-bromoallylation [15] of 31 with boronic ester 32 stereoselectively constructed the C3–OH group to give homoallylic alcohol 33. Next, a successive manipulation by removal of TBS group, CSA-catalyzed ketalization, and DMP oxidation of the

• secondary alcohol to a ketone allowed for rapid construction of bicyclic ketone 34 in high overall yield. The oxidative dehydrogenation of 34 gave α,β-unsaturated bicyclic ketone 35 smoothly. Sequential A-ring construction and functional group modifications of 35 produced the diketone 36. Subsequently, 36

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• propose the biosynthetic pathway, which has not yet been reported in Duh’s isolation report (Scheme 1a). In our proposal, the linear sesquiterpenoid trans-nerolidol (1) with a chiral tertiary alcohol undergoes dihydroxylation to generate triol 2, which further proceeds a C–C bond cleavage to afford

• aldehyde 3. This linear aldehyde would be activated by an acid to trigger a key Prins cyclization with the trisubstituted olefin through reaction model 3 and generate a putative tertiary carbocation to be trapped by the chiral alcohol, providing bicycle 4 stereoselectively. Finally, the last olefin would

• TBS protection in one pot. Oxidation of the primary alcohol using Swern oxidation gave the hydroxy aldehyde 3, which was activated with a formal silicon cation to trigger the Prins cyclization terminated by the tertiary alcohol, affording silylated bicycle 9 directly through the designed bioinspired

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• using the symmetrical dithiophen-2-yliodonium p-tosylate (I-7). It should be noted that all products 8 were obtained with exclusive (E)-selectivity. Tetrahydrofuran 8a and some analogous compounds could be synthesized previously from alcohol 7d, but in two steps, employing a halogen electrophile-induced

• described by us recently, among other possible transformations [21][22]. Interestingly, the addition of O-nucleophiles to form 1,3-carbofunctionalization products, can only be achieved in an intramolecular fashion. In the presence of an excess (5 equiv) of external an O-nucleophile R–OX (alcohol, carboxylic

• internal nucleophiles (Scheme 4), that could be used instead of the alcohol. The carboxylic acid-containing silane 7 (R = COOH), which was obtained by stepwise oxidation of the alcohol 7d, failed to give the desired lactone 8t product due to O-arylation of the carboxylic acid, leading to phenyl alkyl ester

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• synthesis with complete reduction to the alcohol followed by partial re-oxidation often being conducted. Conclusion In conclusion, we have developed novel light-driven methodologies for the reduction of acylazolium salts using benzoylimidazolium triflate as a model substrate. In the presence of a

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• afforded the corresponding alcohol 18 in 89% yield with excellent enantioselectivity (98% ee) [25]. The hydroxy group in 18 was then protected via treatment with TBSCl in the presence of Et3N in CH2Cl2, yielding β-keto ester 15 in 52% yield. With diketone 15 in hand, we subsequently investigated the

• of 21 with allyl alcohol and triphenylphosphine afforded transesterification product 22 in 21% yield [33], accompanied by unidentified decarboxylation by-products. A variety of standard conditions failed to promote the palladium-catalyzed decarboxylative allylation of allylic β-ketocarboxylate

• controlled by the stereoelectronic effect of the axial hydroxy group at C11 (Scheme 4) [28]. First, β-keto ester 21 was synthesized (Scheme 5). Cross-metathesis of allylic alcohol 18 and olefin 28 with the assistance of the Hoveyda–Grubbs second-generation catalyst delivered the desired product 27 in 68

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• intramolecular cyclization of 16 generated benzofuran 17 in 83% yield. After protecting the phenolic hydroxy group of 17, cross-metathesis (CM) with allylic alcohol 18 catalyzed by 13 furnished intermediate 19. Desilylation of 19 produced heliannuol G (20) and heliannuol H (21), with the structure of 21

• 25 with vinyl butanoate and PPL delivered monoester 26 in 92% yield (99% ee). The axial chirality was transferred to the C7’ stereocenter through a Ag(I)-catalyzed cycloisomerization of the allenol, constructing the dihydrofuran ring. Lipase-catalyzed ester hydrolysis provided allylic alcohol 27

• . Alcohol 28 was obtained from 27 in two steps, and was subsequently converted to hyperione A (30) and ent-hyperione B (31) by refluxing in toluene with Shvo’s catalyst 29. Notably, the authors found that hyperione A (30) could be obtained in higher yield and enantiopurity from alcohol 28 via a two-step

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• estimation of the yield of each product (Figure 2, panel B). It was found that many reactions involving alcohol- (e.g., C1–5, C8, C11 and C14) and indole- (e.g., C3, C12 and C15) containing co-substrates yielded intermolecular products, whilst those involving nitrile-containing co-substrates (C9 and 10) and

• reaction modes of dirhodium carbenoids that were possible [14]. Overall, products were formed via O–H insertion into an alcohol (to give 14 products) or phenol (→ 2-4 and 3-4a); N–H insertion into an indole (→ 1-3a, 1-15b, 2-3a, 2-15b and 4-3), sulfonamide (→ 2-6), aminopyrimidine (→ 2-13 and 4-13) or

• were obtained. In the case of co-substrate 3, which contains both an indole and an alcohol, thus raising chemoselectivity issues, products were observed from both O–H and N–H insertion. It is notable, however, that despite many of the co-substrates having multiple potentially reactive sites, one

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• -dipole, access to 1,3-amino-alcohol functionality is possible. This arrangement is present in many Alstonia alkaloids, and we envisaged using this cycloaddition chemistry to set up the bridged amine ring system found in these natural products. Bridged and spirocyclic ring systems are known to be

• the presence of a Lewis acid. The use of BF3·OEt2 gave a low yield of the desired alcohol 2 [29]. This was improved slightly with Sc(OTf)3 as the Lewis acid, which could be used substoichiometrically [30]. The alcohol 2 was converted to the tosylate 3 and subsequent ozonolysis gave the aldehyde 4. The

• ), dried (MgSO4), filtered and evaporated. The residue was purified by column chromatography on silica gel, eluting with EtOAc/petrol 1:2, to give the alcohol 2 (824 mg, 30%) as an amorphous solid; data as reported [30]. Et3N (1.5 mL, 10.8 mmol) was added to the alcohol 2 (782 mg, 3.6 mmol), TsCl (1.03 g

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• applications to functional materials, pharmaceutically relevant compounds, and agrochemicals [8][9][10][11][12][13][14][15][16][17]. In our recent work, we have developed a Torii-type electrosynthesis of unsaturated esters 3a–c starting from furfural (1) and amino alcohol conjugates 2a–c [18]. The process

• proposed mechanism of product 7 formation. Electrochemical oxidation of protected amino alcohol 2d to ester 3d. Supporting Information Supporting Information File 8: Experimental procedures, characterization data and copies of NMR spectra. Funding This project has received funding from the European

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• 72% yield and excellent regio- and stereoselectivity. Regarding the acceptor, compound 6 harbored two free alcohol groups at the C3 and C2 positions. Since the C3 alcohol group is less sterically hindered and exhibits better nucleophilicity, the glycosidic bond formed regioselectively at the C3

• position. Additionally, THF was used as a solvent to enhance the α-selectivity of the reaction [41][42][43]. Next, while both compounds 8 and 9 can act as acceptors, compound 9, a primary alcohol, exhibits greater nucleophilicity. Using the TolSCl/AgOTf promoter system at −70 °C, the β-linked disaccharide

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• . Moreover, an axially chiral tertiary alcohol-phosphine 42 was prepared from 39a through a three-step procedure including N-methylation, reduction of phosphine oxide, and Grignard addition to ester. Subsequently, 42 was applied as a bifunctional Lewis base organocatalyst in the formal [4 + 2] cyclization

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• compound [29] and can be prepared from readily available m-anisyl alcohol by using iodination and bromination reactions (see Supporting Information File 1 for the details). Subsequently, an SN2 reaction between 2 and tert-butyl cyclopropanecarboxylate (3) in the presence of LDA delivered product 4 in 87

• % yield with a cyclopropyl group. Then reducing the carboxylate group in 4 with DIBAL-H afforded alcohol 5 in 67% yield. Next, Sonogashira coupling reaction between 5 and trimethylsilylacetylene generated 6 with an alkyne moiety quantitatively. After that, the hydroxy group in 6 was oxidized into a

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• TMSOTf at 0 °C to room temperature, successfully furnished the desired α-Man-(1→3)-α-Man-(1→3)-α-Man trisaccharide 10 in 87% yield in a one pot manner. Removal of TBDPS group in 10 with 70% HF·pyridine and subsequent phosphitylation of the resulting free alcohol with phosphoramidite 11 provided the

• over the following steps: 1) deprotection of the TBDPS group, 2) phosphitylation of the free alcohol with phosphoramidite 11 in the presence of 1H-tetrazole and 4 Å MS, and 3) oxidation of the phosphite by mCPBA. Hydrogenolysis of Bn and Cbz groups in 14 with Pd(OH)2/C and subsequent saponification of

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• ranging from 51% to 99%, depending on the alcohol and catalyst loading (1–10 wt %). Alcohols with additional functional groups were converted to the respective esters suitable for further modifications. The CS600 catalyst proved promising for the transesterification of low-molecular-weight esters, medium

• , and minor components did not affect the reaction or were inert. Since the transesterification with a catalyst derived from carbide slag (CS600) and commercial (or obtained from another source) calcium oxide proceeds by the same mechanism with the formation of a new ester and an alcohol as byproduct

• processing. Next, the CS600 catalyst was investigated in the transesterification of soybean oil with various alcohols. The overall results of the transesterification are presented in Scheme 1. All the reactions were carried out at the boiling point of the corresponding alcohol, using different CS600 loadings