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

• -10b-hydroxy-6,6,9-trimethyl-1,9-epoxy-6H-dibenzo[b,d]pyran-3(10bH)-one and also propose the common name: melifoliox B for this new natural compound. The stereochemistry of 4 is characterized by the three centers of asymmetry of the isomeric melifoliones at position 6a, 9, and 10a. Since the two

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

• under basic conditions triggered an Achmatowicz rearrangement (shown in Scheme 8, below) to assemble a hydropyranone ring [83]. Eventual acetylation of the free alcohol units afforded 70 in 3:1 dr. C-Glycolysation with allyl-TMS and oxidative cleavage of the PMB moiety yielded 71. The stereochemistry of

• using acetic anhydride. Oxidative cleavage of olefin 73, followed by treatment with ʟ-proline led to an intermediate β-aldehyde with inverted stereochemistry at the β-C (4:1 dr). Subsequent reduction with NaBH4 yielded alcohol 74. Piv-protection of the primary alcohol, reductive deprotection of the Bn

• stereochemistry of the central protected alcohol unit was inverted within a sequence involving deprotection of all acetates, protection of the 1,2-diol as an acetonide, oxidation of the central alcohol with DMP and stereospecific reduction, which yielded alcohol 78. Finally, the silyl protecting group was cleaved

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

• construction of remote biaxial chiral molecules. These strategies enable precise control over the stereochemistry of multiple axes in a single reaction, allowing efficient formation of distal biaxial chiral scaffolds while maintaining excellent enantio- and diastereoselectivity. Recent studies have

• the stereochemistry in a single transformation. This has motivated the development of sequential strategies, in which one chiral axis is constructed first, followed by the introduction of the second axis in a subsequent step. Such stepwise approaches allow precise control over each axis, improving the

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• °C: 24.5 kcal/mol), respectively, which are within the predicted range of stereochemical stability (Figure 6). For the determination of absolute stereochemistry of 1ab and 1ad, we performed HPLC analysis using circular dichroism (CD) detector [17]. The HPLC analyses with OJ-H column of 1ab and 1ad

• shape for the CD spectra of the first eluates, thus we determined that the absolute stereochemistry of the first and second eluates corresponds to the (R)- and (S)-isomers, respectively. Transformation of planar chirality of 1ab to central chirality The planar chirality of the methyl-substituted

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

• aromatic ligand is necessary to set the absolute stereochemistry of the organic product. This relative stereochemistry depends on which face of the arene is coordinated and can be governed by high chiral recognition for binding (coordination diastereomer ratio, cdr) or stereoelectronic differentiation

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

• Dacquet, 1997 An unavoidable challenge for aromatic ring hydrogenations is controlling the stereochemistry of the product during the hydrogenation reduction process. In 1997, Dacquet and co-workers conducted a hydrogenation reduction of the natural product (−)-tabersonine using platinum dioxide as a

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

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• activity [20]. A related metabolite lacking the C7 prenyl group had been isolated from the cultures of Aspergillus chevalieri in 1976 [21]. The structure and absolute stereochemistry were confirmed by synthesis from tryptophan and ʟ-alanine [22]. The isolation of terezine D (6) and more recently, the (3R

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

• dense stereochemistry and, thus, have stood long as benchmarks in chemical synthesis. Recently, these steroid alkaloids gained popularity as challenging targets in total synthesis, with a clear shift toward convergent strategies. Not only do these syntheses feature rapid assembly of their challenging

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• Gabor Berecz Andras Dancso Maria Tothne Lauritz Lorand Kiss Gyula Simig Balazs Volk Egis Pharmaceuticals Plc., Directorate of Drug Substance Development, P. O. Box 100, H-1475 Budapest, Hungary HUN-REN Research Centre for Natural Sciences, Institute of Organic Chemistry, Stereochemistry Research

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

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

• carbonyl, a silyl transform, and oxidation of the C2 secondary hydroxy group afforded intermediate 54. This sequence successfully installed the C3 hydroxy group with the requisite stereochemistry for 3-epi-ryanodol (5). Subsequent introduction of an isopropyl group at C2 and global deprotection yielded the

• C10 stereochemistry, thereby completing the total synthesis of anhydroryanodol (10). By applying established strategies developed by Deslongchamps and Reisman to this intermediate, they enabled the formal total syntheses of ryanodol (4) and ryanodine (1). Summary and Outlook Ryania diterpenoid natural

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

• stereochemistry of substituents, as well as the heterocyclic anomeric unit. Uncertainty regarding the mode of action, along with inadequate synthetic approaches toward a lead compound, remains elusive. The well-established synthetic route reported by Hanessian and co-workers began with ᴅ-ribonolactone which bears

• undesired stereochemistry at C3 due to a possible chair-like transition state like 10a (Scheme 2B). This phenomenon is consistent with the observations from previous syntheses [31][35][36]. We anticipated that late-stage epimerization might invert the configuration once the acyl group is revealed at the C2

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

• regioselectivity (>99:1) and complete preservation of the stereochemistry at both quaternary carbon centers (Scheme 17). Through a series of synthetic transformations, the target products (+)-cuparene (91) and (+)-tochuinylacetate (92) were synthesized from acids 96a and 96b with high regioselectivity. In [53

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

• difference between TS30b (ΔΔG‡ = 0.3 kcal/mol) and TS30a (ΔΔG‡ = 0), resulting in the formation of 31 as a 1:1 mixture of regioisomers (Scheme 5c). In this work, to address unsatisfactory C4 stereochemistry in initial synthesis, the authors introduced a double bond to alter substrate conformation, enabling

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• synthesis. Strategies for asymmetric radical reactions Stereoselectivity in radical reactions can be challenging to control. Many radicals are highly reactive, and radicals moreover have typically low inversion barriers, resulting in no permanent chirality at the radical center. Stereochemistry in radical

• occurred in an anti fashion. Products were obtained with up to 97% ee via catalysis by complexes of magnesium or copper(II) with ligand L1. The absolute stereochemistry of the product could be controlled by a simple change from copper(II) to magnesium Lewis acids while using the same chiral ligand, thus

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• terminal position of various polyketide natural products such as a series of azaphilones including chaetomugilins [14], chaetoviridins [14][15], and some other α-pyrone polyketides [16][17][18] (Figure 1). Among the available strategies for elucidating the stereochemistry of MPO, X-ray crystallographic

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• structures of aspera chaetominines A and B and revision of stereochemistry of aspera chaetominine B Several years after we have had accomplished the abovementioned investigations, Liu and co-workers reported the isolation and structural elucidation of two new alkaloids, aspera chaetominines A (12) and B (13

• chaetominine A (12) and monocyclization product 26 in 31% and 45% yield, respectively. The spectral (1H and 13C NMR) data of our synthetic compound are different from those reported for the natural aspera chaetominine A, suggesting that the originally proposed stereochemistry for aspera chaetominine A (12) was

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

• with an acid and base-promoted saponification inversed the C12 alcohol stereochemistry, which ultimately provided (12R)-hydroxymonocerin. Total synthesis and bioinspired skeletal diversification of (12-MeO)-tabertinggine In 2013, Kam and co-workers reported the discovery of two novel indole alkaloids

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

• effects. Previous studies, summarized in Scheme 3, predicted that a diazenyl diradical (az-DZ) with one broken C–N bond would retain the stereochemistry of the reactant, leading directly to the formation of retained housane. However, this pathway was not observed when dynamical effects were included in

• . At the hopping point (274 fs), both θ₁ and θ₂ are significantly increased (149° and 153°, respectively). Here, all carbons of the methylene bridge are located above the molecular plane, indicating complete inversion of stereochemistry. Using kernel density estimation [101], we found that partially

• dynamically concerted but asynchronous denitrogenation reaction, characterized by breaking one σCN bond in the S1 state and the second σCN bond in the S0 state. After the first σCN bond breaks, the stereochemistry of the carbon bonded to N2 begins to invert, suggesting that dynamic effects promote this

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• stereochemical differentiation should at least be traced to the two pilot atoms that are directly attached, but not within the stereogenic plane – similar to the assignment of stereochemistry for cyclophanes. This way, the asymmetric Pd-catalyzed coupling [19][20] would be assigned as [30] (Scheme 5B and 5C). On

• . Nonetheless, the stereocontrol connectivity index can provide information on the stereochemical properties of reactions, beyond the existing binary (yes/no) stereochemistry classifications in widely used chemical databases such as CAS SciFinder and Reaxys. This exercise applies not only to existing asymmetric

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -triisopropylbenzenethiol (TRIPSH) through a hydrogen atom transfer (HAT) process to afford intermediate 30 [39], which then cyclized to yield product 21. To install the allyl group at C8 with the desired stereochemistry, we treated compound 21 with p-TSA in EtOH at room temperature, and ketal 31 was obtained in 87% yield

• stereochemistry at C9. Therefore, alcohol 32 was subjected to a one-pot Mitsunobu reaction, hydrolyzation, and spirolactonization to give the corresponding alcohol 26 with inversed configuration at C9. Finally, terminal alkene 26 was transformed by Dai’s Ru-catalyzed Z-selective cross-metathesis with 33 [9][40

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

• of an oxime, itself prepared in situ from an aldehyde. The stereochemistry of one of the spirooxindoles was determined by single crystal X-ray diffraction studies via crystallisation using encapsulated nanodroplet crystallisation (ENaCt) protocols. The chemistry involves cascade or tandem

• condensation, cyclisation, and cycloaddition as an efficient strategy for the rapid formation of complex spirocyclic products that could have value for the formation of novel, bioactive oxindoles. Keywords: cascade; cycloaddition; oxindole; spirocycle; stereochemistry; Introduction The Alstonia alkaloids are

• rate of evaporation from a nanolitre solution of analyte encased within oil [33], suitable single crystals were obtained. The X-ray analysis allowed the determination of the relative stereochemistry, as shown in Figure 2. Compound 5a crystallised as a racemic mixture in the space group P21/c. The major

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• thiohydantoin derivatives, since the initial compounds 2 had a predominant Z-configuration. At the same time, for cases 1, 3 and 4, both a synchronous and stepwise mechanism are possible. The discovered stereochemistry of the reaction correlates well with the previously obtained data, when the most

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

• Unless otherwise stated, all BINOL derivatives were used as the (S)-enantiomers and the stereochemistry will not be mentioned further. Synthesis of macrocycles featuring one BINOL unit We first investigated the synthesis of crown ether-type macrocycles M1 which feature a single BINOL unit. Our previous