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

• , albeit with a lower overall yield of 3%. Yang’s bioinspired synthesis of illisimonin A In 2023, Yang and co-workers reported a bioinspired divergent synthesis of illisimonin A and merrilactone A, which belonged to illisimonane-type and anislactone-type Illicium sesquiterpenes, respectively [30]. They

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

• 2,4,4,6-tetrabromo-2,5-cyclohexadienone (TBCD) in CH2Cl2 followed by reaction with allyl alcohol, provided β-bromo acetal 5 in 30% overall yield starting from alcohol 6. With a successful preparation of the cyclization precursor 5, the designed nickel-promoted reductive tandem cyclization was pursued

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

• available (+)-sclareolide (101) as starting compound, from which key alcohol 102 was synthesized in 7 steps. Selective mesylation of the secondary alcohol in 102 followed by semipinacol rearrangement catalyzed by t-BuOK afforded diketone 104 as a pair of epimers at C12 in a 1:1 ratio, with 70% overall yield

• unseparated mixture of abeolupanes 245 and 246, in a ratio of 1.5–3:1, with a total yield of 89%. The interaction of compound 243 with BF3·Et2O in benzene at 70 °C gave a mixture of olefins 245 and 246 in a 1:2 ratio, with an overall yield of 88%. Similar transformations were carried out with methyl

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

• bonds of 83 (Scheme 10). Building block 76 was first obtained in 18% overall yield from β-ketoester 74 through a sequence involving Michael addition, decarboxylation, nitrile hydration, and cyclization under vacuum. Aminoketal 81 – a direct precursor to the oxygen-sensitive α,β-unsaturated iminium 81a

• room temperature, delivering spiroacetal (S)-114 with complete retention of configuration (>99% ee). The subsequent one-pot acetylation generated (S)-115 in 83% overall yield over three steps from (S)-112. The following functional group manipulations of (S)-115 – including debenzylation/debromination

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• been reported in a 12-step procedure starting with glucose in an overall yield of 2% [24]. Enol esters [25], enolates [26], enamines [27][28], and silyl enol ethers [29], some of which can be derived from LGO, have been used in electrophilic fluorination and trifluoromethylation strategies. It was

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• alkane fuels (bicyclopentane, tricyclic alkane and spirocyclic alkane) through hydrodeoxygenation [205][206][207][208][209][210]. A cycloalkane with a density of 0.89 g/cm3 and a freezing point below −60 °C was prepared from CPN and lignin-derived vanillin. An overall yield of 95.2% of mono- and di

• ][80][81]. Keto acetals have been observed as by-products, such as in the work reported by Gupta investigating the acid-catalyzed reactions of DHA with various alcohols (Scheme 17) [82]. Colbran and colleagues reported the conversion of DHA to dihydroxyacetone phosphate in four steps in 27% overall

• yield [83]. In their synthesis the cyclic acetal (2,5-diethoxy-1,4-dioxane-2,5-diyl)dimethanol or its dimethoxy analog was esterified with diphenyl phosphorochloridate in pyridine to give (2,5-diethoxy-1,4-dioxane-2,5-diyl)bis(methylene) tetraphenyl bis(phosphate). Subsequent removal of the phenyl

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

• secondary alcohol to a ketone allowed for rapid construction of bicyclic ketone 34 in high overall yield. The oxidative dehydrogenation of 34 gave α,β-unsaturated bicyclic ketone 35 smoothly. Sequential A-ring construction and functional group modifications of 35 produced the diketone 36. Subsequently, 36

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

• compound 14, an intermediate in our synthesis of (–)-isochaetominine A (4) [63]. Indeed, EDCI/HOBt-mediated lactamization of 14 derived amino acid (not shown) via debenzylation increased the yield of (–)-isochaetominine A (4) from 75% to 91% (Scheme 1). Thus, overall yield of the total synthesis of

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

• synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield. Keywords: asymmetric total synthesis; oxidative radical cyclization; tricyclic prostaglandin D2 metabolite methyl ester; Introduction Prostaglandins (PGs), a family of hormone-like lipid compounds, are ubiquitous natural products

• synthesis of 4 was unsatisfactory because it required nine steps to prepare bicyclic intermediate 25 with an overall yield of just 2.0%. This low efficiency prompted us to develop a more streamlined synthetic route for target compound 4. Second generation asymmetric total synthesis of tricyclic-PGDM methyl

• ] 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

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• adopted using compound 85 as the synthetic intermediate, which was prepared from diol 77 in a four-step sequence with 60% overall yield and 96% ee. In 2003, the Fukuyama group realized the first total synthesis of leustroducsin B, a microbial metabolite with various biological activities, featuring a

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• derivative was easily removed with aqueous washes, thereby obviating the need for column purification to remove the more hydrophobic dicyclohexylurea obtained when DCC was employed to facilitate the reaction. Subsequent removal of the Boc groups with TFA furnished malassezione (1) in an overall yield of ca

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

• desired phosphite, which was further oxidized by 3-chloroperoxybenzoic aicd (mCPBA) at −78 °C to 0 °C, producing the desired phosphorylated fully protected trisaccharide 12 in 79% overall yield over three steps. Removal of all protecting groups in trisaccharide 12 is a challenging task due to the presence

• all Bz groups with 1 M NaOH (dioxane/MeOH/H2O, room temperature). The monophosphorylated trisaccharide 1 was obtained in 60% overall yield over two steps from 12 after purification over a SephadexTM LH-20 column. It was noted that the switch of deprotection sequences (first Bz groups, second Bn and

• all Bz groups with 1 M NaOH successfully produced monophosphorylated tetrasaccharide 2 in 63% overall yield. One-pot synthesis of glycans 3 and 4 Furthermore, we investigated the synthesis of monophosphorylated pentasaccharide 3 (Scheme 3). Orthogonal one-pot glycosylation of Man PTFAI 6 (1.2 equiv

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

• 112 in 33% overall yield, which was then used in a 4-step sequence to produce PF-06878031 in >99% purity and a combined yield of 1,500 kg across multiple facilities. 1.5 Ring contractions Another strategy for oxetane synthesis is a ring contraction of 5-membered rings. There are two main approaches

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

• over 25 steps in 11% overall yield. On the other hand, the efficiency of the process was emphasized by the authors on the utilization of Roche esters 29 and ent-29 to prepare stereochemically pure sulfones 27 and ent-27, respectively. Moreover, the use of the trityl protecting group facilitated a

• . Starting from ent-52, obtained via the asymmetric hydrogenation of 51 using the catalyst (Sa)-50, the previously developed three-steps reaction sequence was adopted and repeated three times, yielding polydeoxypropionic acid 57 in an overall yield of 54%. The iridium catalyst (Ra)-50 was chosen to ensure

• alcohol 58 in 93% yield. This alcohol was then acetylated using acetic anhydride and pyridine reagent. Finally, the resulting acetate 59 was treated with DDQ, affording the target compound 60 in 99% yield, corresponding to an overall yield of 49% over 18 steps starting from 51. Yadav’s approach for

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• reactivity of those two alcohols toward oxidation allowed for the selective conversion of desired alcohol to ketone 24 using PCC, producing a 50% overall yield, while the recovered undesired alcohol could be reverted to 21 by Swern oxidation. Direct enol triflation (Et3N/Tf2O, NaH/PhNTf2, DTBMP/Tf2O, etc

• followed by interception of the lithium enolate with PhNTf2 to give enol triflate 25 in 59% overall yield. The following palladium-catalyzed methoxycarbonylation produced methyl ester 26 in a satisfactory yield of 84%. TIPS-protected allylic alcohol 28 was selected as the appropriate precursor for the α,β

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• was not isolated. Instead, the reaction mixture was concentrated and directly subjected to the subsequent heteroannulation step. This approach proved to be feasible, affording the model pyrazolo[1,5-a][1,4]diazepine 16a in 65% overall yield over two steps (Scheme 4). The tentative mechanism for the

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• in three steps (62% overall yield) from commercially available diethyl acetamidomalonate by an alkylation/hydrolysis/Boc-cleavage sequence (Scheme 1). The development of decarboxylative amidation commenced by examining the published conditions for anodic decarboxylation/etherification [4

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• acidic conditions as key step to construct an aryl-containing quaternary center. The 6/5/6 benzofuran unit was formed through reductive elimination with Zn/AcOH and a spontaneous oxy-Michael addition. This synthesis consists of 8 steps and achieves an overall yield of 13%, making it the shortest known

• steps and achieved 12% overall yield. In May 2024, the Qin group reported the second total synthesis of (±)-simonsol C (Scheme 2) [5]. An effective strategy to form the 6/5/6 benzofuran scaffold was developed which specifically involved a basic dearomatization and reductive elimination with Zn/AcOH to

• construct the aryl and allyl-containing quaternary center, and a simultaneous phenol-initiated oxy-Michael addition to afford the benzofuran unit. This synthesis took 9 steps and achieved an overall yield of 13%. Also in 2024, the Denton group reported another efficient way to access the 6/5/6 benzofuran

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• to give hydantoin H2a with an overall yield of 89%, which indicated complete conversion of the intermediate to the product. Encouraged by the result of the one-pot procedure, we tested the method with amino acids carrying different functional groups on the side chains (Figure 1). Phenol (H2b

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• protecting groups and time-consuming purification steps, that provides preQ1 in 43% overall yield with a purity of >98% (Scheme 2). The approach is based on the cyclocondensation reaction between 2-chloro-3-cyanopropan-1-al (6) (itself obtained from chloroacetonitrile and methyl formate) and 2,6

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• enable an easy separation of the byproduct. Pleasingly, reacting the mixture of 3 and 6 with taurine converted 6 to sulfonate 10 (Scheme 2) that can be removed by a simple aqueous wash with sodium bicarbonate. Whereas taurine may also react with 3, the overall yield of 3 was not affected significantly

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• cyclopentadiene to form the final products 8 and 9. When using cyclopentadiene, it turned out that byproducts III were practically not formed, and the target compounds 4–6, 8 and 9 were isolated in a high overall yield. The moderate yield of compound 7 was due to the partial evaporation of the starting

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

• four-step process involves allylation, Claisen rearrangement, isomerization, and oxidative dimerization. Each reaction step was optimized independently by using either online HPLC or in-line benchtop NMR spectroscopy to afford an overall yield of 67% in 66 iterative experiments over four linear

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• commercially available primary amine, 1-(3-aminopropyl)pyrrolidin-2-one completed the total synthesis of the natural product in an overall yield of 1.5%. The NMR data comparison of the natural product and our synthetic compound was essentially identical. Due to our interest in the identification of potential

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• preparation and host assembly. The synthesis adheres to a two-synthon approach which relies on the connection of two building blocks through a CuAAC click reaction (Scheme 1). Building block S1, the azide, is not modified in this work and the preparation is achieved with an overall yield of 43% via the