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

• considerable interest from synthetic chemists. Although the intricate structures of this family have posed significant challenges to chemical synthesis, more than 30 total syntheses of Illicium sesquiterpenes have been reported until now [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• attention has been devoted to the chemical synthesis of carbazole and its derivatives [9][10][11][12][13][14]. To access substituted carbazole cores for pharmacophores and functional materials, two main synthetic routes are: i) sequential multistep syntheses of selectively substituted carbazoles and ii

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

• .21.187 Abstract Furanoside derivatives are broadly present in the antigenic structures of pathogenic microorganisms and play a key role in their recognition by the host immune system. Despite the high demand for vaccine and diagnostic development, their chemical synthesis remains challenging. During the

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

• all compounds. In this study, we developed a method to determine the absolute configuration of the terminal MPO moiety with high accuracy and sensitivity by a combination of chemical degradation, chemical synthesis, and chiral LC–MS analysis. The applicability of this method was demonstrated through

• absolute configuration of scarce natural products, including heptavalinamide A [11] and poecillastrin C [12][13] by a combination of chemical degradation, chemical synthesis, and liquid chromatography–mass spectrometry (LC–MS) analysis. The 3-methylpent-4-en-2-ol (MPO) moiety is commonly found at the

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• Shuhai Qiu Junzhi Liu Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China State Key Laboratory of Synthetic Chemistry, HKU-CAS Joint Laboratory on New Materials and Shanghai-Hong Kong Joint Laboratory on Chemical Synthesis, The University of Hong Kong, Pokfulam

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• approach in chemical synthesis and drug discovery. Representative examples of bioactive quinolines. C(sp2)–C(sp2) bond-cleavage strategies for quinoline synthesis. Substrate scope of various arylamines and styrenes. Scale-up studies for the synthesis of antifungal agents. Mechanistic investigations

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

• , the chemical synthesis of thiotrehalose analogs [116][117] provides a versatile tool for the construction of therapeutically relevant ligands or inhibitors of carbohydrate-specific innate immune receptors. Synthetic thiodigalactosides and their derivatives have been identified as selective inhibitors

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• the foundational work of Kulkarni, Codée, Boons, and other outstanding groups in their studies on zwitterionic polysaccharides [7][8][9][10][11][12]. Pyruvylation of carbohydrate diols is commonly achieved through acetal substitution in the presence of acid during chemical synthesis. In this process

• for O4-linked synthesis in preparing various PS A1 derivatives. In our research, we carried out the synthesis of the PSA1 molecule as part of a broader effort to validate chemical synthesis methodologies. This work involved verifying our experimental techniques and understanding the underlying

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• scaffold. The chemical synthesis, photophysical properties and suitability for barium tagging will be published in due course. Two possible double beta decay modes. Left: with emission of two electronic antineutrinos (ββ2ν). Right: neutrinoless double beta decay (ββ0ν). General structure of first

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• Academy of Sciences, Kunming 650201, China 10.3762/bjoc.21.122 Abstract Chemical synthesis of monophosphorylated glycan motifs from the antitumor agent PI-88 has been achieved through an orthogonal one-pot glycosylation strategy on the basis of glycosyl ortho-(1-phenylvinyl)benzoates, which not only

• glycosylation, respectively; 2) synthesis of PI-88 glycan motif pentasaccharide via [1 + 1 + 1] and [1 + 1 + 3] one-pot orthogonal glycosylation; 3) synthesis of hexasaccharide via [1 + 1 + 1] and [1 + 1 + 1 + 3] one-pot assembly. Keywords: carbohydrates; chemical synthesis; glycosyl ortho-(1-phenylvinyl

• ]. Here, we report the chemical synthesis of monophosphorylated glycan motifs 1–4 from PI-88 through an orthogonal one-pot glycosylation strategy via strategic combinations of glycosyl N-phenyltrifluoroacetimidates (PTFAI) [57][58], glycosyl ortho-(alkynylbenzoates) [59][60] (ABz), and glycosyl PVB, which

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• enzymatic terpene cyclization and chemical synthesis [30][31][32][33]. Briefly, the carbon scaffolds are forged by terpene cyclases, followed by concise chemical transformations to yield the desired natural products. Here, we describe heterologous biosynthesis of cotylenol by engineering the biosynthetic

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• with pressurized gases (0.01–0.1 kbar). The first reports of using HHP were related to food industry applications [3][4], and later in chemical synthesis [5][6]. While the technique had been known since the late 1800s, and it had become popular in materials science and inorganic synthesis, it has

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

• chemistry [108][109]. Ultra-high vacuum (UHV) conditions on metallic surface allow to observe chemical species which are very reactive and impossible to isolate using classical chemical synthesis. Therefore, it is not surprising that such synthetic techniques have been applied to the synthesis of azulene

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• reliable regioselectivity predictions that are essential for accelerating innovation in materials science and medicinal chemistry. Keywords: C–H activation; chemical synthesis planning; directing groups; quantum mechanics; regioselectivity prediction; Introduction The activation and functionalization of

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• into fragment synthesis, providing a more holistic perspective on borrelidin’s chemical synthesis and biological relevance [50]. However, in-depth works focusing on key fragment optimizations remain limited. Hence, this review aims to address this gap. Review Syntheses of borrelidin fragments Uguen’s

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• , these reactions – particularly tandem processes – are highly effective in constructing both fused and bridged ring systems, offering valuable new tools for chemical synthesis. Future advancements in the field could involve further applications of enamide cyclizations with other nucleophiles or in

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• discipline and pursue novel advancements in the realm of chemical synthesis. Keywords: controllable; divergent; diverse products; switchable synthesis; Introduction In the era of synthetic organic chemistry, divergence can produce stereodivergence (including diastereodivergence and enantiodivergence) [1][2

• tactics in chemical synthesis. Ligand-controlled regiodivergent C1 insertion into arynes [19]. Ligand effect in homogenous gold catalysis enabling regiodivergent π-bond-activated cyclization [20]. Ligand-controlled palladium(II)-catalyzed regiodivergent carbonylation of alkynes [21]. Catalyst-controlled

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• demands solutions that meet multiple targets, such as yield, selectivity, purity, cost, environmental impact, etc. In recent years, the advancement of artificial intelligence (AI), machine learning (ML), and automation has produced a paradigm shift for chemical synthesis optimization techniques. By

• consonant and/or conflicting targets. In addition, the incorporation of lab robotics into chemical synthesis has enabled the development of closed-loop optimization platforms capable of executing optimization campaigns rapidly with minimal human intervention, relieving experimenters from labor-intensive

• trends in the selection of optimization algorithms for chemical synthesis. Finally, we highlight the future directions and opportunities in the field. For an in-depth overview on the topic of chemical reaction optimization, the readers are referred to prominent reviews by Taylor et al. [5], Griffin et al

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• an “azacorannulene”. Working from graph structures based on chemically stable (“group elementary”) nodes is a useful principle in molecular design and chemical synthesis. Such a perspective is important to understand fundamental physical organic molecular properties as well as to predict desirable

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• (1O2) finds many applications in photochemistry and photobiology, e.g., for wastewater treatment, fine chemical synthesis, and photodynamic therapy (PDT) [79][80][81][82][83]. Additionally, after light excitation, porphyrins can also oxidize a substrate by accepting electrons from a substrate molecule

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• ; Introduction Enantioenriched α-allenic alcohols are an important class of chiral building blocks used for the chemical synthesis of biologically relevant molecules [1][2][3][4][5]. Their strength comes from the rich synthetic versatility [6][7][8][9] and biological relevance [10] of the allene functionality

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• morphology of the host, etc. [25]. Sequence and function metagenomic approaches have been reviewed elsewhere and will not be covered herein [26][27][28]. This Perspective focuses on chemical structure metagenomics (Figure 2c), an emerging field that integrates bioinformatics, chemical synthesis, molecular

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• fundamental to advancing technologies that address global challenges in health, sustainability, and beyond. By enabling the production of complex molecules with specific functions, chemical synthesis and catalysis play a key role in innovation across the above-mentioned fields and thus improve our quality of

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• describe a short and efficient synthesis for this type of novel skeleton and to prepare a focused library for these targets C. Further, we will report results on their cytotoxic activities. Results and Discussion Chemical synthesis For the preparation of our targets, we selected a flexible strategy which

• has not been used earlier, should offer attractive potentialities in bioorganic and medicinal chemistry. Extension of these studies are ongoing in our laboratories and corresponding results will be reported in due course. Experimental Chemical synthesis General information All reactions were performed

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• the Open Reaction Database (ORD) [36], an open-source initiative to collect and standardize chemical synthesis data from various literature sources. The ORD allows chemists to upload reaction data associated with their publications, and aims to serve as a benchmark for ML development. However, the ORD

• capture of experimental records of chemical reactions from chemical synthesis papers. This development demonstrates significant advancements in streamlining the data extraction process for chemical research. Implicit data issues and data preprocessing tools The quality of training data is a crucial factor

• enhancing the overall chemical synthesis pathway. They demonstrated the predictive pathway for sonidegib synthesis, but it still required chemical insights to verify the compatibility of the solvents predicted by the global model with the reactants. Moreover, in a multistep synthesis route, the