Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• three contiguous stereogenic centers (Scheme 1A). The pyran ring was constructed by a RCM reaction [16]. Subsequent functionalization of the alkene to install the 1,2-cis-hydroxy amine required 6 steps from the sterically more demanding side. In continuing our recent interest in accessing unusual

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

• under gold(I) catalysis through a substituent-controlled strategy (Scheme 8) [15]. Substrates with heteroaryl substituents underwent 6-endo-dig cyclization via gold-heteroatom coordination, furnishing the lactone-fused pyran scaffold 34 (Scheme 8, path a). Substrates with aryl substituents at the

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

• 50% yield and 99% ee after kinetic resolution using Escherichia coli (Scheme 57) [189]. Other reactions: Yamamoto synthesized 6-hydroxy-2-(trifluoromethyl)-2H-pyran-3(6H)-ones from furfural via trifluoromethylation using the Ruppert–Prakash reagent (TMSCF3), followed by a photo-Achmatowicz reaction

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

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• heteroatom for the synthesis of functionalized oxindoles was also reported in 2013 [3]. In this study, DBU was employed as a ligand and TBHP as an oxidant. A series of ethers, including 1,2-dimethoxyethane, THF, 1,4-dioxane, tetrahydro-2H-pyran, 2,3-dihydrobenzofuran, tetrahydro-2H-thiopyran, and N

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• 18.2 (Me-5') characteristic of a 6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl moiety [18]. The chemical shift of C-1' (δC 171.7) in compound 2 compared to 6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl chloride (δC 176.8) indicated that the 6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2

• -carbonyl group was linked through an ester bond and the only hydroxy group available for this esterification was the one at C-7. This compound was finally elucidated as massarilactone D 3,4-di-O-methacryloyl-7-O-(6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl). For the formation of compound 2, an

• oxa-Diels–Alder reaction between two methacryloyl chloride molecules could have taken place to yield 6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl chloride as previously described [18] before esterification of the hydroxy group at C-7. Compounds 3 (6% yield) and 4 (90% yield) were obtained

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• Constantine V. Milyutin Andrey N. Komogortsev Boris V. Lichitsky N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Pr., 47, Moscow, 119991, Russian Federation 10.3762/bjoc.21.44 Abstract For the first time, the reaction of substituted 2H-furo[3,2-b]pyran-2-ones

• with diverse N-nucleophiles was investigated. It was shown that the direction of the process depends on the type of employed nitrogen-containing reagent. For example, condensation with aliphatic amines leads to 2H-furo[3,2-b]pyran-2,7(3H)-diones bearing an exocyclic enamine moiety. At the same time

• unambiguously confirmed by X-ray diffraction. Keywords: allomaltol; enamines; 2H-furo[3,2-b]pyran-2-ones; pyrazol-3-ones; recyclization; Introduction Substituted furan-2(5H)-ones (butenolides) are widely used as precursors for the preparation of diverse types of heterocyclic compounds possessing various

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• 3aa–ca in good yields (47–69%). On the other hand, the reaction with tetrahydro-4H-pyran-4-one (1d) occurred with a significant decrease in yield, dropping to 11%. The yield is also affected by the number of carbon atoms of the starting cyclic ketone 1. In the case of structure 3ea, which involves 2

• . Next, we evaluated the 5-aminopyrazole 3da prepared from tetrahydro-4H-pyran-4-one, and interestingly the corresponding trifluoromethyl carbinol 5daa was afforded, under both reaction conditions, in good yields (66% and 59% yield, respectively) but with a very low diastereoisomeric ratio (near to 1:1

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• -d]pyrano[4,3-b]pyran-, furo[2',3':4,5]pyrano[3,2-c]chromene-, and furo[2,3-d]pyrimidine carboxylates were obtained from the reactions of alkyl 3-bromo-3-nitroacrylates with representatives of carbo- and heterocyclic CH-acids under simple conditions, without the use of organocatalysts. The structures

• reactions of 4-hydroxy-7-methyl-2H,5H-pyrano[4,3-b]pyran-2,5-dione and 4-hydroxy-2H,5H-pyrano[3,2-c]chromene-2,5-dione with ethynylbenzene [26] (Scheme 3). The possibility of the formation of substituted furan structures is shown by the example of the reaction of nitroalkenes with aliphatic CH acids [27

• furancarboxylates based on the interaction of alkyl 3-bromo-3-nitroacrylates [31] with carbo- and heterocyclic CH-acids of the naphthoquinone, pyran, and pyrimidine series. Results and Discussion We have proposed a synthesis of dihydronaphthofuran-3-carboxylates based on the interaction of alkyl 3-bromo-3

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• -4,4a,5,7a-tetrahydrocyclopenta[b]pyran-3-yl)methanone (9). From 1,3-diphenylpropane-1,3-dione (224 mg, 1.0 mmol), ʟ-proline (6 mg, 0.05 mmol) and cyclopentadiene (330 mg, 5.0 mmol), compounds 8 (136 mg, 45%) and 9 (97 mg, 32%) were obtained as white crystalline solids. Major isomer 8 1H NMR (400 MHz

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• Michael-type addition of 5-aminoindazole to afford the first coupling product XXXVIII. The subsequent intramolecular amination and dehydration then leads to the final product (Scheme 31) [50]. Polycyclic spiroindoline-3,4’-pyrano[3,2-b]pyran-4-ones 43 were synthesized exploiting the three-component

• reaction of isatin, 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one (i.e. kojic acid) and malononitriles or cyanoacetates (Scheme 32) [51]. Compared to other Lewis acids, Cu(OTf)2 proved to be the best. Mechanistically, the process begins with a Knoevenagel-type condensation between isatin and the cyano

• ]pyrazolo[4,3-f]quinolinones 42. Synthesis of spiroindoline-3,4’-pyrano[3,2-b]pyran-4-ones 43. Synthesis of N-(α-alkoxy)alkyl-1,2,3-triazoles 44. Synthesis of 4-(α-tetrasubstituted)alkyl-1,2,3-triazoles 45. Funding This work has been supported by Università degli Studi dell’Insubria and Università degli

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• various tissues, with a prominent expression in the adult brain, where it contributes to metabolic processes, aging, and epigenetic regulation. In this context, the group of Hasaninejad et al. (2017) [49] described the synthesis of spirooxindole, spiroacenaphthylene, and bisbenzo[b]pyran derivatives using

• of the nitrogen in lactams 11 with an oxygen in 12 to influence hydrogen-bond donating properties and synthesis of the benzodioxepinone derivatives via Passerini reaction. MCR 3 + 2 reaction to develop spirooxindole, spiroacenaphthylene, and bisbenzo[b]pyran compounds. Synthesis of ML192 analogs

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• internal oxygen nucleophile and fluoride then sequentially attack the activated alkene, to either form 5- or 6-membered furan or pyran heterocycles depending on the chain length in the substrate. The pyran ring is only formed from the alcohol starting material, presumably because the oxygen is reactive

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• Olivier Lessard Mathilde Grosset-Magagne Paul A. Johnson Denis Giguere Département de Chimie, 1045 av. De la Médecine, Université Laval, Québec City, Qc, G1V 0A6, PROTEO, Canada 10.3762/bjoc.20.208 Abstract In this work, we describe the synthesis of halogenated pyran analogues of ᴅ-talose using a

• halogenated pyrans reveals deviation in the intra-annular torsion angles arising from repulsion between the axial fluorine at C2 and the axial halogen at C4, which increases with the size of the halogen at C4 (F < Cl < Br < I). Crystal packing arrangements of pyran inter-halides show hydrogen bond acceptor

• orbitals. Keywords: organofluorine; pyran inter-halide; solid-state conformation; solution-state conformation; Introduction Polyfluorinated pyran analogues of carbohydrates have attracted attention over the years. This class of glycomimetics has great biological potential with useful applications [1][2

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• tolerated in this consecutive four-component reaction, as the 1,3,4-thiadiazine synthesis competes with the thiazole synthesis. Salicylaldehydes 14 and 4-hydroxy-6-methyl-2H-pyran-2-one (16) can also be used to produce 1,3-dicarbonyl compounds 18 by Knoevenagel condensation and subsequent cyclization. This

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• product of monomer 6. The proposed mechanism is shown in Scheme 2. Anodic oxidation of thioglycoside 6 generated radical cation 11, which was converted to glycosyl triflate 12. 1,6-Anhydrosugar 7 was produced via 4C1-to-1C4 conformational change of the pyran ring to generate cation intermediate 13

• disaccharide 16 was obtained as an exclusive product. The optimized structure of 15 calculated by DFT (B3LYP/6-31G(d)) suggested that the pyran ring preferred the boat conformation because the chair conformation of the pyran ring was controlled by the introduction of the 2,3-oxazolidinone protecting group (see

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• gilvocarcin biosynthesis, the conversion of 3 to defucogilvocarcin M (7), featuring a benzo[d]naphtho[1,2-b]pyran-6-one backbone, necessitates the collaborative actions of GilOII and three additional tailoring enzymes, namely GilM, GilMT, and GilR [9]. To date, all available biochemical data consistently

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• including aldosterone receptor antagonistic [22], anti-inflammatory [23], and anti-HIV [24] activity. Substantial drugs based on spirocyclic tetrahydrofuran and pyran moieties include spironolactone (a multi-target drug that is primarily used to treat high blood pressure and heart failure) [25

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• method for the synthesis of pyrimidines containing an allomaltol unit. The suggested approach is based on the reaction of 2-(1-(dimethylamino)-3-oxo-3-arylprop-1-en-2-yl)-3-hydroxy-6-methyl-4H-pyran-4-ones with cyanamide. The photochemical behavior of the obtained pyrimidines was investigated. It was

• field of terarylenes containing a 3-hydroxy-4-pyranone fragment, in the present communication we investigated the photochemical properties of 2-(4-(4-aryl)-2-(dimethylamino)pyrimidin-5-yl)-6-methyl-4H-pyran-4-ones 9 and 10. It is important to note that the 6π-electrocyclization of 1,3,5-hexatriene

• -hydroxy-6-methyl-4H-pyran-4-ones with cyanamide. Subsequently, the photochemical properties of synthesized pyrimidines were studied. We have demonstrated that a 6π-electrocyclization of the 1,3,5-hexatriene system and subsequent [1,9]-H sigmatropic shift leading to dihydrobenzo[h]pyrano[2,3-f]quinazolines

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• precluded the installation of the pyran ring – and the use of its well-known isomerization to set up important stereocenters [6][9] –, thus imposing the anticipated construction of key asymmetric centers. The following discussion will deal with the stereoselective synthesis of a stereopentade amenable to

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• NMR spectra of the resulting polymers showed significant signals at 6.11–5.92 ppm, 5.93–5.83 ppm, 4.36–4.27 ppm, and 3.92–3.82 ppm. The prepared unsaturated polyacetal was then hydrogenated to give poly(6-ethyl-2,3-dimethoxytetrahydro-2H-pyran). The 1H NMR spectrum of the hydrogenated product showed

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• assignments are based on 1H,1H-COSY, 1H,13C-HSQC and 1H,13C-HMBC experiments. High resolution mass spectra were recorded in positive ion mode unless otherwise noted on a Thermo Scientific Q Exactive Orbitrap. 6-Iodo-9-(tetrahydro-2H-pyran-2-yl)-1-deazapurine (17) 6-Iodo-1-deazapurine (2.89 g, 11.79 mmol), p

• -toluenesulfonic acid monohydrate (TsOH·H2O, 0.34 g, 1.77 mmol) and 3,4-dihydro-2H-pyran (2.98 g, 3.21 mL, 35.38 mmol) were dissolved in 5 mL dry N,N-dimethylformamide and stirred overnight for 16 hours at 60 °C. The reaction was quenched by adding ammonia 25% (4 mL) and was stirred for further 5 minutes. The

• gel chromatography using 20 to 50% ethyl acetate in cyclohexane (containing 2% triethylamine) as gradient. Yield: 1.86 g (48%) of compound 17 as a brownish solid. TLC (ethyl acetate/cyclohexane 1:1, 2% NEt3): Rf 0.38; 1H NMR: (400 MHz, DMSO-d6, 25 °C) δ 1.58 (m, 2H, H2-C(5)-pyran), 1.75 (m, 1H, H(b)-C

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• imidazole 1-oxides. The selected CH-acids to study the scope of substrates were barbituric acid, dimedone, 4-hydroxy-6-methyl-2H-pyran-2-one, 1,3-dimethylbarbituric acid, 4-hydroxycoumarin, and 1,3-indandione. The nature of the CH-acids and 2-unsubstituted imidazole N-oxides did not affect the yield of

• -oxide 32 (2 mmol), aldehyde 33 (2 mmol) and CH acid 34 (2 mmol, barbituric acid) was refluxed in H2O (2 mL) and MeCN (5 mL) solvent mixture for 8 h. bThe mixture of imidazole N-oxide 32 (2 mmol), CH-acid 34 (2 mmol, dimedone, 4-hydroxy-6-methyl-2H-pyran-2-one, 1,3-dimethylbarbituric acid, 4

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• investigated for FPDs: the [4 + 2] cycloaddition with alkenes resulting in pyran-annulated products [27][28][29][30][31][32][33][34] and the [3 + 2] cycloaddition with nitrones resulting in isoxazole-annulated products [35][36][37] (Scheme 2). However, formal [4 + 1] cycloaddition reactions for FPDs remain to

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• 206.6, 154.9, 85.1, 82.3, 59.0, 45.0, 36.5, 32.2, 28.4, 18.1, 12.1 ppm; HRMS (m/z): [M + Na]+ calcd 424.2490; found, 424.2480; [α]D20 +37.4 (c 0.5, CH2Cl2). (5S,6R)-5-Ethyl-6-ethynyl-5,6-dihydro-2H-pyran-2-one (21): Caesium fluoride (290 mg, 1.91 mmol, 1.3 equiv) was added to a solution of the lactone

• ) ppm; 13C NMR (90 MHz, CDCl3) δ 162.5, 148.8, 120.3, 77.4, 76.6, 70.7, 38.7, 22.6, 10.9 ppm; HRMS (m/z): [M + Na]+ calcd 173.0573; found, 173.0572; [α]D20 +132.0 (c 1.0, CH2Cl2). (2R,3S,6RS)-3-Ethyl-2-ethynyl-6-methoxy-3,6-dihydro-2H-pyran (19): This compound was prepared according to reference [18]. A

• pressure. Purification by column chromatography (5% Et2O/pentane), gave 19 as a colourless oil (866 mg, 94%, 91/9 mixture of stereoisomers). Analytical data were in agreement with literature data [18]. (2R,3S,6RS)-3-Ethyl-2-((E)-2-iodovinyl)-6-methoxy-3,6-dihydro-2H-pyran (20): This compound was prepared