Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• the intermediate formate ester. Fluorination of enamine 9a with Selectfluor (SF) resulted only in hydrolysis with conditions adapted from Peng and Shreeves work [28]; and likewise, the base-promoted (KOt-Bu, LHMDS) fluorination of ketone 6 with Selectfluor was unsuccessful. However, when ketone 6 was

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• diazoester 24 to furnish a Co(III)-bonded α-ester radical (α-Co(III)-ester radical) with extrusion of nitrogen was proposed by the authors. Further steps include (a) 5-exo cyclization by α-Co(III)-ester radical and (b) homolytic substitution at the carbon atom by 3-exo-tet-cyclization to generate bicyclic

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

• ] intermediate 62 (Scheme 14, path a). When a less nucleophilic indole was used as the nucleophile, a Wagner–Meerwein rearrangement occurred, leading to the formation of a pyrido[4,3-b]indole product 63. When Hantzsch ester (HEH) was used as the nucleophile, the imine intermediate 62 was reduced to product 64

• Wagner–Meerwein rearrangement from the six-membered spirocyclic intermediate 88. The addition of Hantzsch ester or indole as the nucleophile effectively trapped the imine intermediate 88, preventing Wagner–Meerwein rearrangement and yielding spirocyclic indole framework 90 (Scheme 19, path a). When PPh3

• intermediate 167. Subsequent treatment with triethylamine/pinacol induced ring closure, affording the phenanthreno[1,3-b]cyclobutane borate ester 168. In contrast, when the temperature was elevated to 60 °C, the reaction underwent a BCl3-driven skeletal rearrangement involving methyl migration and alkyne

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• series of molecules: the ones without chlorine in meta position on this group (series a) and the others which kept this chlorine, like in DB18 (series b). These syntheses are reported in Scheme 2. A Suzuki-type Pd-catalyzed coupling of 7a with 4-(methoxycarbonyl)phenylboronic acid dimethyl ester (8) gave

• reagent the 3-(methoxycarbonyl)phenylboronic acid ester 11. All derivatives have spectral and analytical data in agreement with the proposed structures (see experimental section and Supporting Information File 1). Kinase inhibition studies Our molecules have been submitted first to a primary screening

• also evidenced by the better affinity for DYRK1A of the acidic molecules as compared to their ester analogues. Therefore, this new interaction could explain the higher affinity of VS-77 toward Hs_DYRK1A, as compared to DB-18. Conclusion In the present work, we disclosed a new strategy to improve the

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

• the stereochemical assignment of (+)-capsulactone (1). Keywords: chemical degradation; chiral LC–MS analysis; methyl 3-hydroxy-2-methylbutanoate; 3-methylpent-4-en-2-ol moiety; p-nitrobenzoyl ester; Introduction Configurational elucidation of natural products is essential for progress in diverse

• derivatization. Several derivatization methods using chiral anisotropic reagents, including α-methoxy-α-trifluoromethylphenylacetic acid (MTPA), phenylglycine methyl ester (PGME), and Marfey’s reagents, are widely used [8][9][10], although their applicability is restricted by the presence of specific functional

• 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

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• azobenzenes were obtained in purified yields between 70 and 85%. Various functional groups at the ortho- or para-position were well tolerated in this reaction, including electron-withdrawing groups such as trifluoromethoxy (3c, 69%), nitrile (3e, 81%), methyl ester (3h, 74%), N,N-dimethylamide (3i, 73%) and

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• Cotton effects compared with (S)-2a. We consider that the hydroxymethyl group is sterically more hindered than the planar phenyl groups in the conjugates. This tendency is the same as that of the previously reported 1–(S)-2-phenylethylamine conjugates [41]. The CD spectra of 1-ʟ-amino acid ester

• conjugates (S)-2d,e exhibited positive first and negative second Cotton effects indicating that the two long axes in the methoxybiphenyl chromophores constitute a P twist. The methyl ester group is estimated to be sterically more hindered than the planar ester carbonyl group in (S)-2d,e. The CD spectra of

• the methylene protons. In contrast, in the M conformer, the medium-sized methyl group (denoted as M) is located near the seven-membered ring, reducing the steric repulsion involving the hydroxymethyl group with the methylene protons. Moreover, considering that the phenyl ring and the ester carbonyl

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

•  2). Functional groups including ester, azido, and alkynyl present in the starting materials are responsible for the post-Ugi transformations. Results and Discussion We first attempted the Ugi–azide 4-CR at a 0.2 mmol scale with equal molar amounts of 2-azidobenzaldehyde (1a), propargylamine (2a

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

• in 66%–87% yields. Boc-amino ester (2e), dipeptide (2f), apivalate ester (2g) and ethinyl estradiol (2h) skeletons were also tolerated well. According to the previous works [163] and the experimental results, the authors proposed a plausible mechanism. Firstly, the anodic oxidation of [Cp2Fe

• involved at the ethyne moiety like substituted phenyl (30b–e), benzodioxole (30f), naphthyl (30g), thienyl (30h), pyridinyl (30i), furyl (30j), benzofuranyl (30k), alkyl (30l, 30m), cycloalkyl (30n–p) and trimethylsilyl (30r). This reaction was also compatible with benzyl ester (30s), propynyl ester (30t

• rt for 9 h. The reaction was compatible with numerous amines such as substituted benzylamines 46b–d, 1-(2-naphthyl)methanamine 46e, 3,4-methylenedioxybenzylamine 46f, furfurylamine 46g and 2-thiophenemethylamine 46h. Alkynes with ester and trifluoromethyl groups worked well under this reaction

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

• level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims

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

• 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

• hydroxyketone 86 in 60% yield with 92% ee and 8.4:1 dr. A secondary hydroxy-directed Grignard reagent addition of 86 followed by selective protection, generated alcohol ester 87. After one recrystallization, the ee value of 87 could be increased to 99%. Subsequently, TMSOTf-promoted transacetalation and in situ

• ,8R,11R based on the X-ray single-crystal analysis of its corresponding p-bromobenzoic ester (not shown). Total synthesis of (−)-conidiogenones B–F and (−)-12β-hydroxyconidiogenone C Conidiogenones are unique diterpenoids which possess a highly congested 6/5/5/5-fused framework with four all-carbon

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• ], we re-synthesized tripepetide derivative 25 from ᴅ-tryptophan (ᴅ-Trp) and ʟ-isoleucine (ʟ-Ile) methyl ester hydrochloride salt (24) in three steps (Scheme 4). Treating 25 with DMDO followed by work-up with a saturated aqueous solution of Na2SO3 at 30 °C provided the proposed structure of aspera

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• interest, compound 2 applied as a useful substrate for a Baeyer–Villiger oxidation mediated by oxone, which selectively converted the aldehyde to the formate ester, yielding 6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl formate (4). Subsequent hydrolysis of 4 furnished indolo[1,2-c]quinazoline-6,12-dione

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

• reduction of ketone using SmI2 and propionaldehyde provided 15 diastereoselectively. Friedel–Crafts cyclization using trimethyl orthoformate and TMSOTf provided the cyclic acetal moiety to be oxidized with PDC, delivering the isocoumarin skeleton in 16. Chemoselective removal of the ester with the lactone

• underwent dehydroxylation protocol involving base-promoted mesylate elimination and catalytic hydrogenation reactions, providing 31a. Reduction of lactam and ester in one pot with LiAlH4 and acid-promoted hydrolysis of ketal protection to ketone furnished 32a. Finally, oxidation of the primary alcohol to

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

• reaction [17] and a [4 + 2] annulation reaction between o-carboxylic ester-containing diaryl-λ3-iodanes and some terminal alkynes [18]. Looking to expand the possibilities for terminal alkyne carbofunctionalization, we turned our attention to propargylsilanes, which are prone to undergo cationic

• 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

• formation. Its silylated version (7, where R = COOSi(Me)3) only resulted in starting material degradation. Interestingly, tert-butyl ester 7e (R = COOt-Bu) provided the desired arylated lactone 8t, along with the protodecupration product 13, which was formed in excess under the standard arylation conditions

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

• offer many synthetic advantages while the wide availability of chiral NHCs can also allow for high levels of enantioselectivity. As effective enamine and active ester derivatives, Breslow and acylazolium intermediates A and B typically react via classical two-electron polar mechanisms, however, recent

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

• pathophysiological mediator in many human diseases and biological pathways. Tricyclic prostaglandin D2 metabolite methyl ester (tricyclic-PGDM methyl ester), the major urinary metabolite of PGD2, can be used as a clinical indicator for PGD2 overproduction. However, the limited amount of tricyclic-PGDM methyl ester

• available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total

• synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield. Keywords: asymmetric total synthesis; oxidative radical cyclization; tricyclic prostaglandin D2 metabolite methyl ester; Introduction Prostaglandins (PGs), a family of hormone-like lipid compounds, are ubiquitous natural products

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

• 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

• sequence comprising TBS protection, ester hydrolysis, mesylation, and hydride reduction. In 2014, Tokuyama and co-workers accomplished the total synthesis of (−)-petrosin and (+)-petrosin, two marine-derived bisquinolizidine alkaloids [45]. They first completed the synthesis of (−)-petrosin (84) (Scheme

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• agent; glycidyl ester; electrochemical evaluation; phosphorus-containing drug; Introduction Phosphorus-containing drugs represent a crucial category of therapeutic agents, extensively utilized in clinical practice due to their diverse pharmacological properties and applications [1][2][3][4]. These

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

• fumarate was also successful and gave a mixture of the stereoisomeric cycloadducts 7 (Scheme 5). The yield was high and three inseparable stereoisomers could be detected by 1H NMR spectroscopy. In each case we assume that the methyl ester groups are trans to one another due to the expected concerted nature

• of the dipolar cycloaddition process. In contrast, the dipolarophile dimethyl maleate gave predominantly one stereoisomer of the cycloadduct 8 (ratio of isomers 95:5) (Scheme 5). The stereochemistry of the major isomer was assigned from NOESY analysis, that indicated the methyl ester groups were cis

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• asymmetric transfer hydrogenation employing Hantzsch ester HEH-1 as the reductant afforded both helically chiral tetrahydroquinoline derivatives (M)-30 and the recovered aza[6]helicene starting material (P)-29 with good to high enantioselectivity, achieving an s-factor of up to 121 (Scheme 8). Moreover, by

• resolution or dynamic kinetic resolution [40]. The authors designed and synthesized a series of benzaldehyde-containing macrocyclic cyclophanes 38. Therein, they achieved the construction of planar chirality through CPA-catalyzed asymmetric reductive amination with arylamines using Hantzsch ester HEH-2 as

• with allylboronic acid pinacol ester (41) led to efficient kinetic resolution, yielding the recovery of (Sp)-40 with high enantiopurity (Scheme 12). Notably, the allylation products 42, possessing both planar chirality and central chirality, were produced with high enantioselectivity and

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• with the increasing lipophilicity of the alkyl chains, which is a result of the increase in surface area of the alkyl groups [51]. Of further interest are the results of the catalysis under the same neat conditions using the dimethyl ester of our catalytically active linker, Me2-BDC-NH2 (Table S3

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• weaken the hydrogen bonds between N–H and the ester moieties of the rotor and the stator. The Cigáň group focused on the synthesis of benzoylpyridine hydrazones with different substitutions in the rotor benzene [97]. The p-NMe2 group causes red-shift of both absorption maxima of the E- and Z-isomer

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

• composed of MSNs and choline sulfonatocalixarene[2]pseudorotaxane. Two different choline derivatives with distinct structures and lengths (Figure 14) were grafted onto the pores of MSNs via ester or urea linkages, serving as enzyme-cleavable sites. Negatively charged SC4A macrocycles were introduced to

• envelop the choline stems on the surface of MSN-NPs through host–guest interactions, forming pseudorotaxanes as the mobile/cleavable components of the nanovalves. It was experimentally demonstrated that esterase could selectively activate the ester-linked nanovalve (MSN-C1), while urease could selectively

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

• amino alcohols derived from furfural and ʟ- or ᴅ-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare (S)- and (R)-enantioenriched unsaturated amides by N-Alloc deprotection which induced concomitant

• conditions compatible with the double bond and acetal functions. In this work, we present Torii-type electrosynthesis of ester 3d (PG = Alloc) and its transformation to the enantioenriched vinyloxazoline building block 6, which can be used for the asymmetric synthesis of complex molecules [19][20][21][22][23

• ][24] (Scheme 1). The proposed strategy relied on the N-deprotection of the intermediate ester 3d inducing O-to-N rearrangement to form amide 5 as a precursor of vinyloxazoline 6. For this purpose, Alloc (allyloxycarbonyl) turned out to be a suitable N-protecting group as it was compatible with the