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

• . Crystallizations with this compound and the truncated survivin constructs 1–122 and 1–127 were finally successful and yielded high-resolution X-ray structures (Figure 4) [15]. The structures of both survivin truncation mutants look very similar, both have a survivin dimer in the asymmetric unit, and the H3 peptide

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

• and data acquisition. Data collection was therefore applied with seriously elongated exposure time. The crystal structure was successfully solved using methods as implemented in the SHELXT program [16], followed by refinement with SHELXL [17]. The refined asymmetric unit was found to contain about

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• lithiated furanyl unit took place. The so-obtained 1:1 diastereomeric mixture of 68 was treated with (PhO)3PMeI in dimethylacetamide and formed an intermediate trans-olefin, which subsequently underwent an asymmetric Sharpless dihydroxylation. The acetonide was cleaved with AcOH and the addition of NBS

• 166 via radical cyclization, then the TBDPS-protecting group was cleaved and the obtained alcohol oxidized to aldehyde 167. The Cr(II)/Co(II)-induced asymmetric NHK coupling mediated by 172 with vinyl iodide 171 led to tetrahydrofuran 168. Protection of the secondary alcohol enabled the conversion to

• thereafter, Nasam and co-workers developed a novel synthesis of 1`s fragment 272 using multiple asymmetric catalytic transformations (Schemes 29–31) [102]. 256 was synthesized from trans-crotonic acid and served as a starting material for the first building block (261, Scheme 29). Hosomi–Sakurai allylation

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

• distal axial chiralities are widely applied in chiral ligands, natural products, and anticancer agents, with their unique spatial configurations endowing them with distinctive functions and values. Although significant progress has been made in the asymmetric synthesis of distal biaxial chirality

• , Hayashizaki, and Ito reported a highly stereoselective asymmetric cross-coupling reaction of 2-methylnaphthylmagnesium bromide with bromonaphthalene, catalyzed by a nickel complex with ferrocenylphosphine as the ligand, successfully synthesizing biaxially chiral molecules, namely 1,1':5',1"- and 1,1':4',1

• one chiral axis followed by the second, and transformation from central chirality to axial chirality. We anticipate that this review will facilitate the development of novel synthetic strategies for remote biaxial chiral molecules, improve asymmetric synthesis efficiency, and expand their applications

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

• readily available. Additionally, Xiang et al. [17] and Jew et al. [18] reported asymmetric syntheses of taxifolin, which suffer from long-step operation and the use of complicated and expensive metal-ligand catalysts. Currently, the most widely used chemical method is the synthesis of trans-(±)-taxifolin

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• . Indeed, the 1H NMR spectrum of the triazolated tetraurea 49 obtained from its solution in CDCl3 turned out to be overcomplicated (see Figure 4). The spectral pattern apparently arises from the superposition of signals from two asymmetric homodimers, 492 isomer 1 and 492 isomer 2 (Figure 4a), which are

Non-central chirality in organic chemistry

• Ken Tanaka and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24

• Ken Tanaka Naohiko Yoshikai Department of Chemical Science and Engineering, Institute of Science Tokyo, O-okayama, Meguro-ku, Tokyo 152-8550, Japan Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai 980-8578, Japan 10.3762/bjoc.22.24 Keywords: asymmetric synthesis

• axial, planar, or helical chirality individually, often organized along specific molecular classes or application-driven themes such as asymmetric catalysis or chiral materials. In contrast, this Thematic Issue deliberately brings together diverse manifestations of non-central chirality under a single

• complementary roles played by non-central chiral molecules in contemporary organic chemistry. First, they continue to serve as demanding benchmarks for asymmetric synthesis, probing how far stereochemical information can be transmitted and controlled when the stereogenic element is spatially or conceptually

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

• transition-metal-catalyzed asymmetric C–H activation reactions as a directing group, thus necessitating an efficient method for the cleavage of 8-aminoquinoline-derived amides. The role of Me2SO4 in this transformation was elucidated through DFT calculations. Methylation of the carbonyl oxygen by Me2SO4

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• presence of DIPEA in chloroform under reflux (Scheme 2). These conditions ensured complete conversion in 30 minutes. The IR spectra of nitroxides 3a–f exhibit intense absorption bands in the ranges of 1354–1358 cm−1 and 1174–1178 cm−1, corresponding to the asymmetric and symmetric vibrations of the

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• dimension of control: chirality at the metal center. The resulting enantioenriched complexes have enabled a suite of asymmetric transformations (vide infra) [47]. Structure and properties To rationalize and predict the enhanced reactivity of η2-bound arenes, it is instructive to first examine the properties

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

• -opening polymerization of some lactones [26][27] and are important for the syntheses of ionic liquids [28][29] and asymmetric phosphate esters. Furthermore, a novel metal extractant based on diaryl phosphate has recently been reported [30][31]. Phosphate esters are generally synthesized from phosphoryl

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

• asymmetric synthesis, where they serve as chiral ligands and organocatalysts, delivering high enantioselectivities [17][18]. Their tunable HOMO–LUMO gaps and controlled π–π interactions, is key to the use of helicenes in molecular electronics and organic semiconductors as well. Helicenes function as active

• the utility of the parent helicene in diverse areas, thereby offering a more versatile alternative to classical helicene extension strategies. Discussion Only a handful attempts have been made for the asymmetric synthesis of helical molecules using π conjugation extension [28][29][30]. This prevalent

• helical chiral entities was reported by Wang and co-workers. They reported an organocatalyzed asymmetric synthesis of phosphorus-containing chiral helicenes enabled by dynamic kinetic resolution using copper and peptide-mimetic phosphonium salts, i.e. amino acid-derived phosphonium iodide and bromide as

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

• versatile intermediates for enantioselective S–C bond formation under mild and metal-free conditions. Keywords: asymmetric synthesis; late-stage functionalization; selective oxidation; sulfenamides; sulfinimidate esters; Introduction Sulfur is a privileged heteroatom in organic chemistry, celebrated for

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• synthesized and screened in asymmetric Mannich reaction. The reaction of aromatic imines with malonates in the presence of amino acid-derived catalysts gave Mannich adducts in very high enantiomeric purities (up to 98% ee). It is proposed that a network of hydrogen and halogen bonds with Lewis bases, together

• with the steric effect of the tert-butyl group of the catalyst, is responsible for the high stereoselectivity of the reaction. Keywords: aromatic imine; asymmetric catalysis; Mannich reaction; noncovalent interactions; organocatalysis; Introduction The Mannich reaction, i.e., the addition of an

• been used in the synthesis of numerous pharmaceuticals and natural products [7]. The application of asymmetric synthesis enables access to enantiomerically pure targets. Earlier, metal catalysis was used for Mannich reactions [8][9], but in recent years, methods of asymmetric organocatalysis have been

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• asymmetric ones [23]. Organic dyes are also used as chemosensors, which provide economical, fast, and equipment-free analysis for the detection of environmental pollutants affecting the environment and human health [24][25]. Colorimetric detection of specific ions like cyanide, which is considered a highly

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• bromine. The cyclization step from this conformation leads to trans-cyclopropanes. X-ray diffraction analysis data for compounds 2, 3, 9a, and 9b convincingly confirm the accepted structures, the position of cyclopropane protons, and the relative configurations of asymmetric atoms (Figures 2–5). It should

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

• , isoquinoline, pyridine, and related substrates can now be reduced with high efficiency and stereoselectivity, providing efficient access to saturated and partially saturated architectures vital to synthetic chemistry. Furthermore, catalytic asymmetric aromatic hydrogenation has facilitated the asymmetric total

• ][19][20]. In recent years, promoted by the rapid development of asymmetric catalysis, a wealth of reactions applicable to aromatic systems – including substitution reactions, transition-metal-coupling reactions, and even dearomatization [21][22][23] – have been reported, further extending their

• systems. In addition, converting a planar sp2-hybridized-atoms-enriched framework into three-dimensional sp3-hybridized-atoms-enriched architectures inherently generates new stereocenters, making stereocontrol essential in asymmetric variants. As highlighted in the methods below, recent advances in

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• octahydropyrido[1,2-a]pyrimidinones is caused by the appearance of an additional asymmetric center in the starting 1,3-diaminopropan-2-ol, as opposed to the reactions with 1,3-diaminopropane [24]. The diastereoselectivity of cyclization with acetophenone depends on the reaction conditions: in the absence of a

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

• -methylene group and an ester reduction/Appel reaction sequence to convert the ester moiety to an iodide leaving group. The right-hand fragment (E/F-ring) was synthesized from tert-butylsiloxyfuran 39. Commencing via an asymmetric allylic alkylation and an aza-Michael reaction, butanolide 40 was obtained in

• moiety was introduced as a precursor to an aldehyde, which was obtained by reduction of 46 to 47. For the right-hand fragment (ring D, E, and F), an asymmetric hydrogenation of α-substituted acrylic acid 48 was performed, followed by redox manipulations to give aldehyde 49 over 3 steps in 95% and an

• enantiomeric excess of 92%. This asymmetric hydrogenation included a novel iridium catalyst featuring a chiral SpiroBAP (spiro bidentate aminophosphorane) ligand, which has been developed previously by this group and was now successfully applied in this synthesis [36]. A silver-catalyzed, enantioselective

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

• crystal XRD analysis confirmed the presence of the expected products and the stereochemistry of the newly created olefinic compound as being Z, as expected. Compound 3n crystallizes in the monoclinic crystal system with four molecules in the asymmetric unit whereas 4n crystallizes in the triclinic crystal

• system with two molecules in the asymmetric unit. The bond distances in 3n C1=O1 is 1.229(4) Å and C2=S2 is 1.629(4) Å. For compound 4n, the observed C=O bond length is shorter than that of compound 3n (1.202(2) and 1.221(2) Å), respectively (Supporting Information File 1, Table S3). Intermolecular

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• asymmetric reactions and are functional transformations in synthetic organic chemistry. Especially, 1,2,3-triazole-based NHCs are generally more reactive and stronger σ-donors than imidazole or thiazole analogues. Triazolium NHC enhances their ability to stabilize reactive radical intermediates or acyl anion

• , Michael additions, cycloadditions, domino reactions, cascade annulations, Diels–Alder reactions, and Michael–Stetter reactions, to name a few [31][32][33][34][35]. Notably, previous reports have demonstrated that the utility of chiral N-heterocyclic carbene (NHC) catalysts permits contracting asymmetric C

• and heteroarenes using blue LED. Asymmetric synthesis of fused pyrrolidinones via organophotoredox/N‑heterocyclic carbene dual catalysis. Acknowledgements Vasudevan Dhayalan expresses his appreciation to DST-SERB for core research grant (CRG/2022/001855), and to the National Institute of Technology

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

• was conclusively revised to 1S,4S,5S,6S,7R,9R,10R. Kalesse’s asymmetric synthesis of illisimonin A In 2023, Kalesse and co-workers reported an asymmetric synthetic route to illisimonin A [29]. The Kalesse group also noticed the strained trans-pentalene in illisimonin A. Since there is a spiro

• hydroxy group could be responsible for this reversal in selectivity. Dai’s asymmetric synthesis of (−)-illisimonin A In 2025, Dai and co-workers accomplished an asymmetric total synthesis of (−)-illisimonin A in 16 steps from (S)-carvone (67) using a pattern-recognition strategy and five sequential olefin

• encumbered tricyclic lactone 84 via an intramolecular [6 + 2] cycloaddition (Scheme 8). Attempts to achieve an asymmetric version of the cycloaddition were unsuccessful. Treatment of the lactone with MeMgBr, followed by mesylation and elimination of the resulting hemiacetal, afforded enol ether 85. Reaction

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• core, successfully completing the first asymmetric total synthesis of ryanodol (4) in 41 steps. To elucidate the role of the C15 hemiacetal hydroxy group in ryanodine (1)-type diterpenoid natural products in binding to ryanodine receptors, the authors initially proposed reducing the lactone moiety in

• ). Furthermore, from intermediate 57, the introduction of an isopropyl group at C2 and subsequent deprotection furnished cinnzeylanol (6). Reisman’s total synthesis of (+)-ryanodine (1), (+)-20-deoxyspiganthine (2), and (+)-ryanodol (4) In 2016, the Reisman group at Caltech reported an asymmetric total synthesis

• , epoxidation of the C1–C2 double bond, and Li/NH3-promoted reductive cyclization to construct the core E ring, completing the asymmetric total synthesis of (+)-ryanodol (4). The 800-fold greater binding affinity of (+)-ryanodine (1) for cardiac ryanodine receptors (RyRs) compared to its hydrolysis product

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• Abstract The total synthesis of bioactive (+)-aglacin B was achieved. The key steps include an asymmetric conjugate addition reaction induced by a chiral auxiliary and a nickel-promoted reductive tandem cyclization of the elaborated β-bromo acetal, which led to the efficient construction of the

• synthesis of both enantiomers of aglacins A (1), B (2), and E (4) by asymmetric photoenolization/Diels–Alder reactions as the key steps for the construction of the C7–C8 and C7′–C8′ bonds [8]. During the past decade, we had developed nickel-catalyzed or -promoted reductive coupling/cyclization reactions for

• that the diarylmethine stereocenter at C7′ in 6 could be formed by an Evans’ auxiliary-induced asymmetric conjugate addition of α,β-unsaturated acyl oxazolidinone 7 with 3,4,5-trimethoxyphenylmagnesium bromide (8). Both of these two building blocks could be conveniently prepared from commercially

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

• (III) and iodine(III), and Wolff rearrangement. 2.1 Benzilic acid and semipinacol-type rearrangements The strategy of ring contraction using the benzilic acid-type rearrangement was used by Zhang et al. [38] for the asymmetric synthesis of 4β-acetoxyprobotryane-9β,15α-diol (52). This compound contains

• aldehyde 53 [39] (Scheme 10). The key steps in this synthesis are based on an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction [40], followed by a unique benzilic acid-type rearrangement under very mild conditions [41]. A step-by-step mechanism for the benzilic acid-type rearrangement of