Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• turned to peptide tweezers with longer linkers to address lysines which are buried neither in the crystals nor in the CPC complex. In a second approach, one of the tweezer phosphate groups was truncated to minimize steric hindrance during the tweezer approach towards survivin’s α-helix within the CPC

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

• geminal methyl groups in the pyran ring can fold more easily to avoid the steric hindrance caused by the ethane bridge above the pyran rings. Consequently, these methyl protons resonate at similar field strength. The high field shift of H-10a in 4 is a result of the loss of its benzylic position (Table 1

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• comparison of the synthesis and photophysical properties of the fluoro-substituted norbornadiene 1f with the ones of the parent compound 1b revealed that the yield of the Suzuki–Miyaura coupling reaction is significantly lower for the former [22], presumably because of the steric hindrance induced by the

• , [Ru(phen)3]2+ (2.19 eV) [53] does not catalyze the reaction of 1f, but is still able to catalyze the one of 1b [50]. Notably, the half-life of trisquadricyclane 2f0,3 (55 d) is almost eight times longer than the one of the parent compound 2b (8 d) [22], presumably because of additional steric

• hindrance induced by the fluoro substituents in the ortho positions [54]. It should be noted that there is only very limited data available to compare the effect of the substitution pattern on the half-life of aryl-substituted norbornadienes to support this interpretation [55]. However, the effect of ortho

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• donor atoms, a carbonyl oxygen and a hydroxy oxygen, that can simultaneously coordinate to a uranyl ion [77]. In supramolecular systems, not all hydroxamic acid groups necessarily bind uranyl ions, as steric hindrance and site accessibility can limit coordination to a subset of available sites [78]. A

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

• stoichiometric conjugation with suitable substrates. The small size of Au–NH2 minimizes steric hindrance and allows for enhanced spatial resolution, relative to colloidal nanogold particles, thereby facilitating high precision labeling of the HDAC active site. CI-994 was synthesized using previously established

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• "-ternaphthalene compounds [35]. This work significantly advanced the development of bi- and multiaxial chirality. The synthesis of multiaxial chiral molecules requires appropriate steric hindrance to elevate the rotational energy barrier of each chiral axis [36], and the spatial interactions between axes are

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• moieties (such as bis- or tris-MOMO-substituted phenyl substituents). Due to the steric hindrance, the trans-configured product with the phenyl substituents on the opposite side of the epoxy functionality is obtained. Additionally, the clean reaction process shown by TLC and the NMR spectrum of the product

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• , such methods often exhibit limited substrate scope, generally restricted to amides with low steric hindrance, such as DMF or DMAC. In recent years, several new strategies have emerged to overcome these limitations: (i) transition-metal-free activation using electrophilic reagents, (ii) strong-base

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• 2c in comparison to the other substrates due to steric hindrance. In addition, when 1i and 1j were used, the corresponding phosphate ester 2i was not obtained at all, and 2j was formed only in a low yield. It is well known that phenols containing strong electron-withdrawing groups can be good leaving

• pyrophosphate ester intermediate because of its steric hindrance, and the yield of diaryl phosphate was low. Phytic acid extraction and phosphate ester synthesis The extraction of phytic acid from rice bran was based on a study conducted by Ida et al. [1]. As rice bran generally contains rice bran oil, it was

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

• heteroanalogues. These challenges include: (1) the limited availability of suitable substrates, (2) substantial steric hindrance from the terminal ring, making it difficult to introduce substituents at the required positions onto helical precursors, and (3) the complex nature of controlling helical chirality, a

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• due to the stronger donor character of the pyrrolidine moiety due to its planar structure. The formation of the deacetylated products 2n,o (Scheme 2) may be attributed to increased steric hindrance, which makes proton transfer to B in Scheme 6 more difficult. The dimethyl-1-yl moiety likely exhibits a

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• excellent yields (77–92%). Notably, ortho-substituted sulfenamides gave consistently high yields (3l–o, 87–92%), indicating excellent tolerance toward steric hindrance. These results suggest that the reaction is largely insensitive to both steric and electronic effects, underscoring its broad functional

• sulfinimidate esters in good yields. Encouragingly, the method also tolerated bulky acyl groups such as adamantyl (3x, 88%) and 1-naphthylmethyl (3y, 99%), which underwent smooth conversion without significant steric hindrance. A series of benzamide-derived sulfenamides bearing various substituents on the

• were obtained with 87% and 88% yield, respectively, indicating that steric hindrance at the ortho-position does not adversely affect the transformation. Meta- and para-substituted derivatives, regardless of their electronic nature, also reacted smoothly to afford the corresponding products 3c’–g’ in

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• ). During attempts to reduce intermediate 181 via asymmetric hydrogen atom transfer (HAT), the authors found that 181 exists as a racemic mixture, with chirality originating from its axially chiral biaryl structure. Owing to the steric hindrance introduced by substituents, 181 exists as a pair of

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• in refluxing toluene, giving 99 in 88% yield as a single diastereomer. Due to steric hindrance, dienophile 98 would approach the more accessible face of diene 97, i.e., cis to C8–H. Furthermore, exclusive endo-addition was observed because exo-addition would lead to severe interference between the

• afford cyclization of the E-ring. The obtained pyridinium species was directly reduced to reveal the piperidine moiety. The observed selectivity for hydrogenation from the α-side was attributed to the steric hindrance of the C20 axial tertiary TMS ether. The survival of the olefin in the D-ring was

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

• introduce another side chain, affording a diene intermediate. A subsequent ring-closing metathesis (RCM) reaction formed the cyclopentene ring, and one pot protection of both carbonyl groups with ethylene glycol provided bis-ketal 55. Notably, due to steric hindrance, only one carbonyl group could be

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• , which indicates that steric hindrance at C2 has a limited effect on the reactivity. However, when the steric hindrance of the protecting group was increased by replacing –Cbz with –Boc, the activity of the PET reaction decreased, which resulted in a lower yield of 10f (45%). In the case of substrate 9g

• the formation of benzyl radical IN2, which has a boat-like seven-membered ring. This structural feature may facilitate formation of the C19–C12 bond, even in the presence of critical steric hindrance between the C5 quaternary carbon and the indole moiety. Further DFT investigation proved challenging

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• . Third, the introduction of an ortho-methyl substituent on the ketone moiety (3m) likewise suppressed product formation, likely due to steric hindrance interfering with cyclization at the C3 position of the indole ring. Based on literature precedents [15][16], we propose a mechanism involving a radical

• only minor limitations attributable to steric hindrance or functional group sensitivity. Antimicrobial evaluation of the synthesized spirocyclic compounds revealed no significant activity against the tested microbial strains. However, the synthetic versatility and broad substrate scope of developed

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• variations in fluorescence properties, leading to deviations from the linear Stern–Volmer relationship governing the quenching mechanism. The flexible benzene ring of the PBG allows the cavity to be conformationally adjusted to fit the size of I−, while the rigid fluorenyl group of the WDG results in steric

• hindrance, with a 95.6% lower binding constant of KWDG/KPBG = 0.044, a difference that can be attributed to the synergistic effect of induced fit (PBG) and conformational selection (WDG). Fluorescence emission spectra further corroborated the response of PBG and WDG to iodide ions (Figure 3c and 3d). When

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

• conformational preference at C8 that favors 1,5-HAT occurring at C9. (2) In terms of stereoselectivity, the steric hindrance between the spin center at C14 and the axial methyl group at C10 restricts the rotation around the C13–C14 bond, thereby enabling the diradical to undergo coupling stereoselectively. As a

• , substituent effects, and steric hindrance. Meanwhile, for multi-functional group substrates, the presence of potential competitive hydrogen transfer sites tends to lead to the formation of non-target cyclized products, further reducing the reaction specificity. Dicarbonyls are excellent substrates for Norrish

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

• could be further derivatized (e.g., via borylation, epoxidation), establishing a versatile platform for accessing fused-ring natural products. Substituent-controlled cyclization of 1,n-enynes In transition metal-catalyzed cyclization reactions, the electronic properties and steric hindrance of

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

• -catalyzed side-reaction. As shown above, the steric hindrance plays a significant role in driving the reaction. For this reason, we have applied our novel Pd methodology to synthesize a series of tetra-, tri-, and di-ortho-substituted azobenzenes (Scheme 3). Notably, this method demonstrates remarkable

• (allyl)2 in DME with strong base (Cs2CO3) favors C–N-bond coupling, which may yield products resulting from arylation at either the terminal or internal nitrogen atoms. The selectivity can be influenced by the steric hindrance of the phosphine ligands and/or the substrates. Once N,N-diarylhydrazine is

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

• and transformations of 43 produced hydroxyketone 44. Due to the steric hindrance of this substrate, the subsequent Suzuki cross coupling reaction with 3-boronophenol proceeded in low yield. To address this issue, Han′s group employed a novel palladacycle catalyst 45, previously developed by their

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

• bioinspired synthetic approach [44]. Initially, we prepared a bicyclic precursor similar with toussaintine C to react with α-phellandrene to mimic the bioinspired Diels–Alder reaction, which, however, showed no reactivity due to the strong steric hindrance. To decrease the steric effect, we finally used

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• -molecule azobenzene derivatives achieve gravimetric energy densities of 300–400 J/g with long-term storage stability. However, solvent dependence or steric hindrance in multiazobenzene units remains an inherent challenge dictated by material type. These materials show promising applications in device

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• may arise from increased steric hindrance imposed by the methyl group on the methylene bridge of the derivatives. Two clusters represent the partially inverted hopping point, depending on which σCN breaks first. The second type, referred to as the inverted hopping point, occurs when both dihedral