Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• spectra (Scheme 7b). A remarkable feature of the 13C NMR spectra of compounds 3n and 4n in DMSO is the attenuation/absence of peaks corresponding to the carbon atoms at the ortho and meta positions of the six-membered ring. It is known that quaternary carbon atoms have very long relaxation times, but this

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

• deketalization afforded carbonate 58. A palladium-catalyzed decarboxylative alkenylation reaction was then carried out across the less hindered face of the six-membered ring to connect C5 and C6. Selective deprotonation and triflation at the C4 carbonyl group provided enol triflate 59. An intramolecular

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

• , particularly iridoids. One of the promising methods for ring contraction in the absence of multiple bonds in the six-membered ring of terpenoids was proposed by Grishko et al. [26] (Scheme 6). The key step of 2,3-fragmentation was the cleavage of an enolized C–C bond at a keto group, followed by an

• ) (Scheme 11). The technique of regioselective oxidative contraction of a six-membered ring was described in the work by Luo, Zhang and co-workers [43] during their synthesis of the natural alkaloids, dactylicapnosines A (63) and B (64), which contain a 9,10-seco-7-dehydroaporphinoid skeleton with an

• , yield, and ratio of reaction products (Scheme 35). The authors [88] suggested that the 1,2-oxirane was opened by the Lewis acid at the first stage. This is accompanied by the contraction of the six-membered ring and the formation of an intermediate D. The spatially close reactive centers in molecule D

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

• -strain between the methyl group at C10 and the substituent at C8 restricts the free rotation of the C8–C13 bond (although this steric hindrance can be circumvented through chair–boat isomerization of the six-membered ring, the barrier for this isomerization is relatively high), resulting in a

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

• cyclization, yielding a six-membered ring product 72 (Scheme 15, path b). This observed selectivity arose from differential stabilization of transition states by ligands, thereby enabling the Au(I)-catalyzed cyclization to directly access bioactive heterocyclic frameworks commonly encountered in natural

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

• of 57 to phenolic intermediate followed by the construction of the B ring generated tricyclic core 59. Subsequently, dihydroxylation of the doubled bond in the central six-membered ring using OsO4/NMO gave diol, which was then subjected to acetylation of the two hydroxy groups and hydrogenation of C5

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

• product 85l with slightly lower yields. Interestingly, N-methyl-N-arylcinnamamides proved to be efficient substrates, leading to the smooth formation of the corresponding six-membered-ring products 86a,b with acceptable yields and good diastereomeric ratios (dr). A key innovation of this work was the

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• . It contains a six-membered ring and is, like its five-membered correlate, known for its secondary structure inducing properties, which are particularly useful in the design of peptide conformations. We present a new and improved way to generate enantiomerically pure pipecolic acid derivatives with

• structure of pipecolic acid is rather challenging and often necessitates early-stage derivatization followed by the formation of the six-membered ring [29][30][31][32]. An alternative is to utilise derivatization reactions such as Suzuki–Miyaura [33] or Sonogashira–Hagihara [34] cross-coupling reactions on

• acid (7-ACA) from cephalosporin C by cephalosporin C acylase [37], was used as a chiral starting material. After esterification of both carboxylic acid functions followed by cyclization to the lactam [38][39], the six-membered ring structure was established as (R)-methyl 6-oxopipecolate (7) with a high

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• involves the regioselective nucleophilic attack of allylaluminum C on tosyl cyanide, which proceeds at the γ-position via six-membered ring transition state D, leading to the formation of the desired nitrile product. Transition state D is responsible for the E-selectivity observed in trisubstituted allenes

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• aspects. We will first consider how fluorination can affect the ring pucker (Figure 9). For pyranoses (i.e., six-membered ring sugars), the classic 4C1 chair conformation is usually strongly preferred. This conformation tends to be maintained even if one or several fluorines are introduced as replacements

• protonated amine. These conformational changes alter the DNA-binding mode, such that the pyrrolidine NH groups of 95 now interact with the DNA phosphates rather than the bases or the sugars [164]. Progressing now to a six-membered ring system, consider the scaffold, pipecolic acid (96, Figure 11) [165][166

• ]. This molecule is a ring-expanded analogue of proline, and derivatives of it are found within several natural products and drugs. The pucker of the six-membered ring of 96 is quite important for bioactivity, because different puckers project the carboxyl substituent in different orientations (equatorial

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• -assisted departure of the leaving group, the lone pair of electrons of the nitrogen atom of the pyridine fragment of the Pic group participates to form a stable oxocarbenium intermediate 91 through the formation of a six-membered ring. The glycosylation mechanism proceeds via an SN2-like pathway through

• as a protecting group [153] for the C-2 position which successfully formed a six-membered ring intermediate via neighbouring group participation to form completely selective 1,2-cis glycosylated products with a range of carbohydrate acceptors. The formation of ring intermediate and glycosylating

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• -fluorinated analogs [38]. It is anticipated that the introduction of a CF2 could eventually stabilize the conformation of the six-membered ring via stereolectronic interactions of the CF σ* orbitals with the neighboring CH σ orbital [40]. The 180° FCCH dihedral would rigidify the six-membered ring. We present

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• of different and particular structures [7][8]. Additionally, glycans can adopt a wide variety of different shapes; five-membered ring sugars can exhibit envelope and twist conformations usually represented on a pseudo-rotational wheel; while six-membered ring structures can adopt chair (C), boat (B

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• the difference in such reactivities are intramolecular cyclizations (Scheme 1). A radical cyclization generates a five-membered ring with a less-stable primary radical, while a six-membered ring with a secondary cation is obtained through ionic cyclization. When such intramolecular cyclizations are

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• polymeric version of 2-iodoxybenzoic acid (PS-IBX), was conducted to block the formation of the six-membered ring. Spiro-1,3-oxazolidinones 63 were assessed as inhibitors of 17β-HSD type 3, an enzyme involved in testosterone and dihydrotestosterone synthesis. The structure–activity relationship revealed

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• been shown to be dependent of the chemical structure of the dopant. Triazines are a class of heteroaromatic compounds with three nitrogen atoms on a six-membered ring, with the general formula C3N3H3. According to the position of the nitrogen atoms in the ring, they constitute 1,2,3-, 1,2,4- and 1,3,5

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• 0 kcal/mol for more clarity. Herein, one chlorine atom is transferred from aluminum to the hypervalent iodine(III) center through six-membered-ring transition state TS1–Cl (ΔG‡ = 9.7 kcal/mol, selected bond lengths 2.76, 1.22, 1.27, 1.78, 2.60, and 2.86 Å for I–O, O–C, C–O, O–Al, Al–Cl, and Cl–I

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• transformations in a single reactor, reducing the number of steps and the amount of waste with consequent benefits of cost and environmental impact [42][43]. Representative examples of relevant N-fused heterocycles. Different acid-catalyzed six-membered ring cyclizations. Substrate scope for the assembly of

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• -membered ring products. They isolated cyclic five to seven-membered ring products by changing the lengths of the diols. For example, for the formation of cyclopentane products, butane-1,4-diol was used as the alcohol under the same reaction conditions, giving 31 to 70% yield of the desired products. Seven

• intramolecular BH reaction for the formation of cycloalkanes from ketones and 1,n-diols [66]. Different substituted 1,5-diols were coupled with 1-(2,3,4,5,6-pentamethylphenyl)ethan-1-one using 4 mol % of catalyst Mn13 and 2 equiv of t-BuOK as base in t-AmOH at 140 °C for 36 h to give 51–98% yield of the six

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• transformation of the five-membered pyrrole ring in compound 2 to the six-membered ring in compound 1 is particularly intriguing. For this transformation, three hypotheses are considered. One suggests that the methyl modification at the oxygen atom of the succinimide ring occurs first, which is then followed by

• gene cluster for compounds 1 and 2, highlighting ShnA, ShnB, ShnC, ShnD, and ShnE as core genes. B: The diagram proposes biosynthetic pathways for compounds 1 and 2, detailing three potential mechanisms that could convert the five-membered ring structure of compound 2 into the six-membered ring

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• recognized as valuable synthetic tools in organic chemistry [54], with the most famous S-extrusion process to generate new C–C bonds probably being the Ramberg–Bäcklund reaction [55]. In the case of heteropines, chalcogen extrusion leads to a six-membered ring via the intramolecular formation of a C–C bond

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• methyl groups in the six-membered ring formed in the cycloaddition and coming from the starting diyne 1a (highlighted in red in Scheme 2). In contrast, for the minor isomer (green dots), which has Cs symmetry, the two methyl groups (highlighted in green in Scheme 2) appear as a single peak at δ = 2.40

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• of H-1/H-2/H-3 and H-6/H-7/H-8/H-9, suggesting the existence of two spin systems. The HMBC correlations (Figure 2) of H-1/C-5 (δC 148.3), H-3/C-4 (δC 126.8), C-5 and H3-15/C-1 (δC 40.6), C-5, and C-10 (δC 36.2) indicate the presence of a six-membered ring. Additional HMBC correlations of H-6/C-4, C-5

• , H-7/C-5, and H3-15/C-9 (δC 43.0) allowed us to assign another six-membered ring, as shown in Figure 2. Furthermore, the positions of a methyl group at C-10 were clarified by the HMBC correlations of H3-15/C-1, C-5, C-9, and C-10, respectively. In addition, the HMBC correlations of H-3/C-14 (δC 174.9

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

• to forge the desired six-membered ring through a key C–C bond formation while furnishing secondary radical VI and the undesired seven-membered-ring compound VII. Closure of the photoredox catalytic cycle would then involve either SET reduction of the radical VI and VII (which upon protonation would

• involved in the biosynthetic formation of the central C ring of several DMAT derivatives. The results presented here lend strong credence to decarboxylation and cyclization to form the six-membered ring as well as the nature of the stable oxidized intermediates concerned. Moreover, unprecedented and