Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• Bestmann ylide-enabled one-step construction of the butenolide motif, a late-stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction. We believe this chemoenzymatic synthetic strategy will inspire future endeavors towards the practical synthesis of complex steroids and other bioactive

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

• diterpenoids; synthetic strategy; total synthesis; Introduction Organic synthesis, as a cornerstone of chemical research, is dedicated to constructing complex natural products or target molecules from simple and readily available starting materials via a series of precise and efficient chemical reactions

• -ryanodol, cinnzeylanol, and cinncassiols A,B In 2014, the Inoue group at the University of Tokyo reported a synthetic strategy for ryanodol (4) that leveraged substrate symmetry design, employing intramolecular radical coupling and olefin metathesis as key steps [46] (Scheme 4). Recognizing an embedded

• present substantial challenges in developing a unified synthetic strategy capable of accessing diverse members of this family. The Zhao group recently achieved the first total synthesis of the Ryania diterpenoid garajonone (8) and its epimer 3-epi-garajonone. Unlike the representative ryanodine

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

• , The Ural Branch of Russian Academy of Sciences, Goleva St. 13, 614081 Perm, Russian Federation 10.3762/bjoc.21.183 Abstract A synthetic strategy for the preparation of spiro[indoline-3,2'-pyrrolidine] derivatives has been developed, featuring a two-step sequence consisting of the reaction of 2

• 25922, E. coli ATCC 8739, and Klebsiella pneumoniae ATCC 700603. Notably, none of the tested compounds demonstrated significant antibacterial activity against the evaluated strains (for details, see Supporting Information File 1). Conclusion In summary, we have developed an efficient synthetic strategy

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• toward vibralactone. Impressed by the unexpected biosynthetic pathway, our synthetic strategy also aimed to construct the quaternary center in the late stage. The retrosynthetic analysis of vibralactone (6) is descripted in Scheme 2. Initially, we proposed that vibralactone could be synthesized from

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

• )-catalyzed transformation to afford tetracyclic products 99 (Scheme 20, path c). This allenylation reaction provided efficient access to functionalized indole derivatives by regulating catalyst systems and substituent patterns. In 2010, the Iwasawa group established a stereoselective synthetic strategy

• aromatic enyne precursors, where product selectivity was controlled by the catalytic system employed. In 2014, Ma and co-workers disclosed a regioselective synthetic strategy for carbazole derivatives, where the directionality of alkyl migration was modulated by the choice of transition metal catalysts

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• ]. Results and Discussion Chemical syntheses The synthetic strategy is very similar to the one previously developed for the preparation of DB18 and designed analogues (Scheme 1) [23][24]. It starts from known quinazoline 1 which, on Buchwald–Hartwig-type reaction with 3-bromoaniline (2a), gave

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

• for the synthesis of (+)-26 to complete the first total synthesis of (+)-chamaecydin (27). The successful collective total synthesis of the two structurally complex natural products demonstrated the high efficiency of the modular synthetic strategy based on the desymmetric enantioselective reduction

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

• generation of our synthetic strategy to chaetominine-type alkaloids featuring two modifications of the last step of our 4 to 6-step approach. Firstly, by employing EDCI/HOBt as the coupling system for the last step of the one-pot O-debenzylation–lactamization reaction, the overall yield of our previous total

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• position 12 [23]. The most straightforward synthetic strategy for formation of an carboxamide group at position 12 of the indolo[1,2-c]quinazolin-6(5H)-one (1) scaffold involved a two-step sequence: (1) carboxylation of the nucleophilic C12 position, followed by coupling with appropriate amines. To

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

• strategies have emerged as an effective synthetic route for the stereocontrolled construction of diverse, highly functionalized bioactive and pharmaceutical molecules [35][36][37]. The herein adopted synthetic strategy, employing photoredox-catalyzed radical cyclization, is illustrated in Scheme 4. Compound

• ] to provide compound 4 in 8% overall yield over 9 steps starting from the readily available compound 16 [41]. Conclusion In conclusion, we developed a synthetic strategy using a radical Csp3–H cyclization, including Snider oxidative radical cyclization and photoredox-catalyzed radical cyclization, to

• synthetic strategy toward PGDM methyl ester 4. Retrosynthetic analysis for the first generation synthesis of PGDM methyl ester 4. Synthesis of bicyclic ketal 25. Retrosynthetic analysis for the second-generation synthesis of tricyclic PGDM methyl ester 4. Asymmetric total synthesis of tricyclic-PGDM methyl

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

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

• this point, the application of BINOL-based crown ethers with 3,3'-appended ethylene glycol chains remains underdeveloped, partially due to the lack of simple and high-yielding synthetic routes. Thus, we believe that our newly developed optimized synthetic strategy will enable further applications of

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• target molecule. This route can provide new derivatives for further searching new SERMs. The synthetic strategy can be applied to other molecules with [3.2.1] framework. Of the same importance, the gram scale (4 g) of the [3 + 2 + 1] reaction with 87% reaction yield demonstrates the practical use of this

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• , respectively [19][20]. Recently, our group established an efficient synthetic strategy for strained macrocyclic polyarenes, such as compound C, in which o-phenylene units preorganize adjacent heteroaromatics into close proximity, thereby facilitating oxidative ring-closure reactions [21]. Among these, the

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

• with limited chemical transformations is highly desirable and should enable the discovery of new fusicoccane derivatives with improved biological activity. Inspired by the biosynthetic machinery of terpenoids, we have reported a hybrid synthetic strategy for accessing bioactive terpenoids by combining

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• single-electron pathways. This duality has enabled access to previously elusive molecular transformations, positioning copper at the center of modern synthetic strategy. This thematic issue captures the dynamic nature of the field, featuring five insightful Review articles and five original research

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• properties in helicene-based materials, advancing their applicability in next-generation optoelectronic devices. In 2020, Pittelkow’s group developed a unique synthetic strategy that converts a non-planar hetero[7]helicene into a planar hetero[8]circulene featuring an antiaromatic cyclooctatetraene (COT

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• with alcohol C–H functionalisation, thus creating a unique synthetic strategy towards oxetane formation that avoids tedious multistep substrate preparations (Scheme 7) [42]. It can be initiated from simple, unactivated primary or secondary alcohols, tolerates various functional groups such as acetals

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

• by Jutz and Kirchlechner in 1966 (Scheme 3) [36]. Condensation between phenalene 15 and pentafulvene 16 gave pentafulvene 17. Pentafulvene 17 was finally subjected to Ziegler–Hafner reaction in quinoline at 180 °C, resulting in the π-extended azulene 18 in 60% yield. A similar synthetic strategy was

• , the synthesis of more complex molecules may require elements of both strategies. Construction of the azulene moiety in the final step Oxidation of partially saturated precursors: With modern cross-coupling reactions providing access to larger precursors, a synthetic strategy involving the

• synthetic strategy was used by Jiang and co-workers for the synthesis of very stable non-alternant nanographene with a triplet ground state [41]. Zhang and co-workers reported the synthesis of diazulenorubicene 29, a non-benzenoid isomer of peri-tetracene (Scheme 5) [42]. The stepwise oxidation of compound

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

• -butanediol 46c, and revised their synthetic strategy as shown in Scheme 5. The synthesis was restarted by treating the pre-cooled (−78 °C) THF mixture of sulfone ent-27 and epoxide 46a with n-butyllithium in a molar ratio of 1.5:1:2.5 (Scheme 6). After warming the mixture for 15 minutes to approximately −40

• applications in medicinal chemistry. Chemical structure of borrelidin (1). Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41]. Preparation of monoacetates 37 and ent-38 by Uguen et al. [41]. Preparation of sulfones 27 and ent-27 by Uguen et al. [41]. Attempts to couple

• sulfones 27 and ent-27 with epoxides 23a–c reported by Uguen et al. [41]. Modified synthetic plan for Morken’s C2–C12 intermediate by Uguen [41]. Revised synthetic strategy for Morken’s C2–C12 intermediate 20 by Uguen [41]. Iterative synthesis of polydeoxypropionates developed by Zhou et al. [40

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• abundant chiral pool building block provides an entry into ᴅ-pipecolic acid derivatives. However, the synthetic strategy is of course applicable to ʟ-aminoadipic acid as well. The minor diastereomer of the catalytic hydrogenation was assigned as (2R,6R)-9, based on the analysis of the coupling constants

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• were observed. However, purification was not possible. Furthermore, an alternative commonly used synthetic strategy involving the Diels–Alder reaction of a pre-functionalized push–pull acetylene with furan or pyrrol derivatives proved unsuccessful [4][43]. All synthesized NBD derivatives were

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• . Synthesis of heteroaromatic systems One of the most powerful applications of MCRs is the synthesis of heterocyclic compounds and several reports in recent years showed the advantages of using this tool as a synthetic strategy to generate complex molecular scaffolds with medicinal relevance [25][26][27]. In

• the most used one. This is usually done at a load of 5 mol % in CH3CN as solvent and CH2Cl2 as a C1 synthon, under moderate reaction conditions (60 °C). Consequently, this synthetic strategy is less dependent on temperature compared to AAA coupling [62]. Several reports also showed that gold (as AuCl3

• reported using an alternative synthetic strategy [92], but lower efficiency in terms of yields, number of steps, and scope compared to this multicomponent methodology. Inspired by this previous work, Sharma et al. improved the reaction for free and immobilized glyoxylic acid, with and without acid

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• hydroamination and temporary protection of nitrile and phenolic hydroxy groups. The synthetic strategy enabled the efficient synthesis of the substructure of saframycins bearing isoquinoline and THIQ units in just four steps from the modular assembly of the three components. We also found the unexpected

• modular synthetic strategy involving the cascading assembly of the left THIQ segment. A concise modular synthetic process was developed to construct the substructure 14 of saframycin A (1), featuring copper(I)-catalyzed three-component coupling, and subsequent tandem 2,3-diaminobenzofuran formation

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• trifluoro/difluoromethylated tetrahydropyridazine acids. Synthetic strategy to obtain fluorinated tetrahydropyridazines from difluoro- or trifluoromethylated hydrazones. X-ray diffraction of compound 8f. Reported syntheses of tetrahydropyridazine ester derivatives. Synthesis of fluorinated hydrazones 3a–f