Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• conditions, affording 9-hydroxy-13-ketocasbene (10, 21%) and 5-hydroxy-13-ketocasbene (11, 20%), respectively, as single diastereomers. Although the orientation of the newly introduced hydroxy group could not be assigned solely based on NMR analysis, the 5-hydroxy group of 11 will be transformed into a

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• -consistent modelling of molecular structures [47]. DiffLinker is an example of a conditional diffusion model developed by Correia and co-workers that enables linking of multiple fragments in a predefined orientation [37]. After pretraining on linkers extracted from molecules originating from several compound

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• closest to this opening was therefore identified as the optimal site for structural modification. To allow more flexible functionalisation, the linking region was redesigned to introduce a secondary amine adjacent to the original amide position. This amine maintained the length and orientation of the

• may underlie this outcome. PROTACs frequently fail because the protein of interest and E3 ligase cannot adopt a productive orientation for ubiquitin transfer. Steric constraints, linker vector misalignment, or insufficient linker flexibility may prevent formation of a catalytically competent ternary

• complex. The azide–alkyne-derived triazole linkage may also impose a rigid orientation not compatible with CK2’s topology. Moreover, PROTACs typically display reduced cellular permeability owing to their high molecular weight and polar surface area [12]. This is particularly relevant given that CAM4066

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• cyclohexane ring to deviate from a chair to a twisted boat conformation by rotating around the C-7/C-8-axis. As a result, the orientation of the geminal protons at these positions can change more easily between a pseudo-axial (ax) and a pseudo-equatorial (eq) position, and the difference in chemical shift

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• , the intrinsic flexibility of the CoREST complex has limited the achievable resolution in cryo-EM reconstructions, making it difficult to confidently assign the orientation of the HDAC catalytic domain relative to LSD1 [10]. Understanding the spatial positioning of the HDAC active site within the

• synthesize a nanogold-conjugated HDAC inhibitor and evaluate its applicability in single-particle cryo-EM to unambiguously determine the positioning and orientation of the HDAC active site within the CoREST complex. Results and Discussion Design and synthesis of a HDAC inhibitor–nanogold probe For the basis

• HDAC1 and LSD1, and thus the spatial relationship of the Au–(CI-994) probe to the LSD1 active site. Hence, although the probe localized to the CoREST complex, unfortunately, the positioning and spatial orientation of the HDAC catalytic domain could not be unambiguously determined. Conclusion In summary

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• another, with a Se···Se distance of 3.703 Å. The second is a selenium–carbon (Se···C) interaction as shown in Figure 2c, where the molecules are arranged in a top-down orientation [54]. In this orientation, the Se motif of one molecule interacts with the carbonyl carbon of another molecule, showing the Se

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• interactions (typically σCH → σ*CF) that stabilize conformations in which the C–F bonds adopt a gauche orientation relative to polar bonds, such as C–N or C–O [8][9][10]. In DFMO, the difluoromethyl group is directly connected to the ornithine backbone, and its conformation is expected to be shaped not only by

• -energy structures (1–4) differ mainly by rotations about the C–COOH, C–NH2, and C–C(NH2) bonds. As a result, their relative energies are governed primarily by the local environments of these groups rather than by the orientation of the difluoromethyl unit. Steric analysis based on exchange energies

• together with Lewis-type effects control the orientation of the difluoromethyl group, are summarized in Table S1 (Supporting Information File 1). As expected, σCH → σ*CN is the dominant interaction (>3 kcal mol−1) and is present in all type-I structures. When these interactions are summed for each

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• each other via hydrogen-bonding interaction, locking the relative orientation of the substrates producing the chiral [4]carbohelicene via peri-terminal functionalization (Figure 2). To examine the utility of the developed protocol, the reaction was scaled up to a 2 mmol scale and the product was

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• -to-ligand charge transfer (MLCT). Furthermore, chiroptical measurements by circular dichroism (CD) and CPL spectroscopy indicated that the axial chirality of the binaphthyl moiety governs the relative orientation of the Pt(II)-based chromophore pair, generating MLCT-band CD and CPL signals through

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• previous reviews that have addressed this class of compounds in part or within broader contexts. Figure 3 offers a structured overview of prior reviews to facilitate orientation within the existing literature. The earliest comprehensive account is found in Jacobs’ 1949 Organic Reactions chapter, “The

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

• emission spectra of 3n in different solvents (10−5 M) at room temperature. d) Lippert–Mataga plot showing Stokes shift as a function of solvent orientation polarizability (Δf) for compound 3n. Photophysical study in aqueous solution under different pH values for compound 3n (10−5 M) at room temperature. a

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• orientation, the distribution of nitrogen atom centers within the ring system appears essential for eliciting bioactivity. Orientation of isoquinoline and N3-triazole subunit nitrogen atoms is identical between 17 and 35 as well as between 18 and 36. In contrast, 34 showed toxicity towards Gram-positive

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

• differences in structure and mechanical properties likely explain the distinct behavior of the rotaxane in these two membranes by influencing its optimal orientation and positioning and, consequently, its ability to modulate the dye release. Figure 6 summarizes the sulforhodamine B release from LUVs with four

• was added to the LUVs. LUVs without sulforhodamine B were used for UV–vis spectroscopy studies. a) Illustration of rotaxane 4 in its preferred orientation within a lipid bilayer; percentage of sulforhodamine B released from LUVs containing rotaxanes 1 and 4; b) without light irradiation, and c) upon

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• energies of starting methyl β-galactopyranoside structure 1 were computed. The initial orientation of the methyl aglycon was chosen so that the torsional angle H1–C1–O1–C(Me) had the value of +40° for the β-structures and −40° for the α-isomers. The benzoate substituents at positions O-2 and O-3 were

• furanoside forms exhibit π–π interactions between the phenyl rings of some benzoate substituents. These are benzoates at O2 and O3 in the pyranoside and benzoates at O2 and O6 in the furanoside. Obviously the orientation of the C5–C6 in the furanoside greatly influences the possibility of such an interaction

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• feature of the structure of G2W1 is the distinctly non-planar triphenylene walls. This non-planarity is likely tied to the constraints of the preferred inward orientation of the OCH3 groups, but also to the need to alleviate steric interactions between Ar–Hf and OCH3 substituents in the bay region of the

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

• , 52.7, 39.4, 26.8; HRESIMS (m/z): [M + H]+ calcd for C18H21N2O6, 361.1400, found: 361.1404. Representative oxindole alkaloids. Orientation for the cycloaddition (left) and the crystal structure of the major stereoisomer 5a (right) with the anisotropic displacement parameters drawn at 50% (oxygen – red

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

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• polarity, with these effects varying based on the amount, position, and orientation of the fluorine substituents [7][8]. Mondal and colleagues have extensively reviewed additional properties of fluorinated cyclopropanes, including the conformational behavior of substituents attached to a fluorinated

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• adapt a gauche-conformation (∠O3–C21–C22–O4 = 66.9(3)°, ∠O4–C23–C24–O5 = −77.3(2)°), and only the central ethylene glycol can be found in a trans-conformation (∠O5–C25–C26–O6 = −173.0(5)°). Probably induced by the linker, the commonly preferred perpendicular orientation of the naphthyl-units in the

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• orientation has proven both efficient and reliable [56][57][58]. The axial C2-OH group in the tribenzylated Man-derived lactol 23 was utilized to trap the anomeric oxygen in the β-configuration via a five-membered stannane ring in 24 (Scheme 3). Subsequent glycosylation with the trichloroacetimidate donor 25

• remains a critical challenge, for which several strategies have been developed. Some approaches employ specialized reagents to lock the anomeric hydroxy group in an axial or equatorial orientation, while others rely on the strategic placement of specific protecting groups at remote or neighboring

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• same absolute configuration. The |glum| value of 7 was 0.4 × 10−3 (Figure S18A, Supporting Information File 1), which was lower than that of 6. In the case of the film states of 6 and 7, low PL brightness and intermolecular random orientation of fluorophores resulted in noisy CPL signals. The CD

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• is consistent with monolayer islands of planar molecules [33]. It is also noted that the molecular islands are typically oriented by ≈0°, 120°, and 240°, with respect to the long edges of the islands. The angles of orientation are determined using a 2D fast Fourier transform (2D FFT) of high

• -resolution images, and an example is shown in Figure 2d. The resonances in the 2D-FFT are originated from the moiré pattern of the super-lattice. Two distinct orientations are visible in the 2D-FFT. The 3-fold orientation of islands suggests that the molecular lattices are oriented with respect to the

• is to be noted that the fluorine atoms are oriented toward the aromatic and aliphatic hydrogen and the carbonyl group to aromatic hydrogen. This suggests possible directional non-bonding interactions between the molecules. For molecules with 3-fold symmetry, the 3-fold orientation within the assembly

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• -workers (Scheme 20) [98]. The starting polymer 152 was synthesized using Suzuki cross coupling and is regiorandom, meaning the orientation of the azulene units within the main chain is not defined. Polymer 152 was annulated using MsOH (methanesulfonic acid) yielding the non-alternant graphene nanoribbon

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• °, displaying a closer arrangement of two HIMs. In contrast, the sodium complex exhibits a more open orientation of two HIMs with an oxygen–sodium–oxygen bond angle close to 167.98°. Lastly, a comparative study of association constants and binding energies for phenylalanine-based HIM with LiBArF20 and NaBArF24