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

• aglycone sarmentogenin in 7 steps from 17-deoxycortisone. The synthesis features a scalable enzymatic C14–H α-hydroxylation, a Bestmann ylide-enabled one-step construction of the butenolide motif, a late stage Mukaiyama hydration, and a stereoselective C11 carbonyl reduction. Keywords: cardiac glycosides

• reactive C17 side chain including an α-hydroxycarbonyl group, a set of side reactions (e.g., reduction of the C20 carbonyl, hydrogenation of Δ4 and Δ14 double bonds, etc.) occurred under the Mukaiyama hydration conditions [30][31]. Therefore, it was necessary to alter the side chain before installing the

• . Therefore, we decided to perform the Mukaiyama hydration on advanced intermediates. Next, a K-selectride-promoted chemo- and stereoselective reduction of the C3 carbonyl of 9 was realized to solely deliver 11 in 85% yield [33]. Then, 11 was subjected to Mukaiyama hydration conditions. Under the Fe(acac)3

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

• scaffolds for several synthetic or natural compounds [5]. Five-membered heterocycles include the thiazolidinone nucleus, characterized by two heteroatoms and a carbonyl group on the fourth carbon, as seen in compounds like rhodanine and thiazolidine-2,4-dione derivatives (Figure 1). These privileged

• ], tetrahydrobenzo[b]pyrans [68], and pyrrolo[3,4-c]quinolinediones [69]. EDDA favors the enol formation of the thiazolidinone (2) through hydrogen donation from the protonated amino group, thus facilitating its removal and formation of enol ii (Scheme 4). This enol adds to the carbonyl group of the aromatic

• tautomerization within the structure of the products, likely induced by the presence of the 4-diethylamino (4-NEt2) group, a strong electron-donating substituent. The canonical structure of thiazolidines, due to the presence of one or two carbonyl groups, thiol groups, and α-hydrogens, allows the formation of

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

• chemistry. In particular, dual catalysis combining N-heterocyclic carbenes (NHCs) with organophotocatalysts (e.g., 4CzIPN, eosin Y, rhodamine, 3DPAFIPN, Mes-Acr-Me+ClO4−) has emerged as a powerful photocatalytic strategy for efficiently constructing a wide variety of carbonyl compounds via radical cross

• carbonyl compounds and pharmaceutically relevant intermediates. Moreover, this catalytic system operates under green and sustainable conditions, tolerating a broad range of functional groups and substrate scope, and utilizes low-cost, atom-economical, non-toxic starting materials. Keywords: dual catalysis

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

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

• , obtained as a 1.7:1 mixture of diastereomers after protection of one of the carbonyl groups in 19 as enol ether with BOMCl. A silyl-tethered intramolecular Diels–Alder reaction of the in situ generated 22 constructed the tricyclo[5.2.1.01,5]decane core bearing a cis-pentalene unit, yielding compound 23

• introduce another side chain, affording a diene intermediate. A subsequent ring-closing metathesis (RCM) reaction formed the cyclopentene ring, and one pot protection of both carbonyl groups with ethylene glycol provided bis-ketal 55. Notably, due to steric hindrance, only one carbonyl group could be

• deketalization afforded carbonate 58. A palladium-catalyzed decarboxylative alkenylation reaction was then carried out across the less hindered face of the six-membered ring to connect C5 and C6. Selective deprotonation and triflation at the C4 carbonyl group provided enol triflate 59. An intramolecular

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

• ABCD tetracyclic core skeleton 71. Treatment of 71 with SeO2 effected a multi-site sequential oxidation, and subsequent triflation yielded triflate 73. Finally, compound 73 underwent a sequence of transformations: introduction of an isopropyl group at C2, directed reduction of the C3 carbonyl

• , and introduction of an isopropenyl group afforded compound 75. Subsequent protection of the vicinal diol as a boronic ester and diastereoselective reduction of the C3 carbonyl group yielded compound 76. Esterification with acylating reagent 77 under basic conditions, followed by boronic ester removal

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• into the calixarene skeleton to develop anticancer derivatives, including proline [34], carbonyl amide [35], glycoureido [36], ureido [37], picolylamine [38], 5-bromopentyltrimethylammonium bromide and 3-bromopropyltriphenylphosphonium bromide [39], among others. Isothiouronium salts represent another

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• with the highest probability. The snapshots in Figure 7 reveal problems with the Db bases in the binding pocket. As discussed earlier, each Db base has a linker containing an NH moiety aimed at forming a stabilizing hydrogen bond with the carbonyl from the linker of the adjacent PNA M-base. Such a

• from glutaric anhydride [30]. In fact, molecular dynamics simulations did confirm that the amide carbonyl of the linker forms a stable H-bond to the amino group of C (Figure 7C). Since the distal guanosine in the C–G base pair is a mismatch with the isoorotic acid binding moiety, the isoorotamide

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

• -ketoxime 45 by Grignard reduction alkylation, followed by a Beckmann fragmentation of the C2–C3 bond of the intermediate 3-ethyl-substituted hydroxyimino ketone in the SOCl2-CH2Cl2 system. The introduction of a carbonyl substituent into the isopropylidene fragment of ketone 46 was achieved either by

• ring contraction reaction on simple cyclohexanones to synthesize functionalized di- and triquinanes [51]. Treatment of 6-oxabicyclo[3.2.1]octan-8-one 86 with BF3·Et2O (2 equiv) promoted the activation of the carbonyl group in 87 by the Lewis acid, leading to the formation of an oxocarbenium ion 88

• hydroxyketone 207 using the Diels–Alder reaction and the ring contraction reaction of epoxyketone 208. After treatment with TMSOTf in dichloromethane at −78 °C, epoxyketone 208 was subjected to selective cleavage of the epoxide, followed by а 1,2-shift of the carbonyl group and the formation of the ring

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• form selective hydrogen bonds between the carbonyl oxygen of the fumaramide unit and the N–H groups of benzylic amide rings. Upon isomerization to the cis isomer, the hydrogen-bonding interactions are weakened, enabling the macrocycle to migrate to a second recognition station [61]. Despite their

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

• ][2][3]. These studies revealed distinct reaction types, with the Norrish type II reaction being one of the most extensively characterized. The mechanism underlying the Norrish type II reaction proceeds via the following steps (Scheme 1a): photoexcitation of carbonyl compound A generates an excited

• congested benzofuranone-based 4,5-spirocycle [26]. Starting from Wieland–Miescher ketone (18, Scheme 4), the synthesis proceeded through a sequence of transformations: the nonconjugated carbonyl was chemoselectively protected as ketal 19; the unprotected ketone then underwent α-methylation to provide 20

• . Notably, 116 resisted oxidation to 118, presumably due to carbonyl-induced π-electron depletion, whereas compound 118 proved resistant to direct conversion into preussomerin EG3 (99) under various conditions. Alternatively, preussomerin EG1 (97) was obtained in 83% yield over two steps from preussomerin

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• substituents – performs significantly better than G2W2 and displays very good removal efficiency for methylene violet. Previous researchers have shown that dye adsorption is promoted by hydroxy, carbonyl, methoxy, and aldehyde substituents which provides an explanation for the better performance of G2W1

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

• pathway-controlled approach using tryptamine ynamides bearing Michael acceptor moieties as substrates (Scheme 27) [38][39]. Under strong Brønsted acid catalysis, protonation of the carbonyl group was achieved, which facilitated a Michael addition between the electron-rich indole C3-position and the

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

• ). Second, molecular docking using DYRK1A crystal structure was used to understand the unexpected binding on the DYRK kinases (Figure 6). Surprisingly, another lysine (K175) is also located near the acidic group of VS-77 (at 3.2 Å between the carbonyl carbon atom and nitrogen from amine). This residue is

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

• –MS detection of the MPO-derived fragment and to achieve a separation of four candidate stereoisomers. To this end, methylation of commercially available methyl acetoacetate (2) and subsequent reduction of the ketone carbonyl group was carried out to prepare a mixture of four stereoisomers of methyl 3

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• conjugates (S)-2d,e exhibited positive first and negative second Cotton effects indicating that the two long axes in the methoxybiphenyl chromophores constitute a P twist. The methyl ester group is estimated to be sterically more hindered than the planar ester carbonyl group in (S)-2d,e. The CD spectra of

• the methylene protons. In contrast, in the M conformer, the medium-sized methyl group (denoted as M) is located near the seven-membered ring, reducing the steric repulsion involving the hydroxymethyl group with the methylene protons. Moreover, considering that the phenyl ring and the ester carbonyl

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

• of Science and Technology, 1037 Luoyu road, Wuhan 430074, China 10.3762/bjoc.21.165 Abstract The carbonyl group is central in organic synthesis, thanks to its ability to undergo a vast range of different chemical transformations on its carbon center or at the neighboring positions. Due to the high

• level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims

• at illustrating how the chemistry of biobased carbonyl platform molecules with backbones from C2 to C6 offers opportunities to reach all kinds of chemical architectures, sometimes even complex ones benefiting from the ability of the carbonyl group to be involved in multicomponent reactions. Keywords

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

• ]. Given the presence of the indole moiety in indolo[1,2-c]quinazolin-6(5H)-one (1), the design of novel gramine-like analogues via aminomethyl substitution at position 12 is feasible. To evaluate the influence of the urea carbonyl group on biological activity, a modified scaffold, 6-methylindolo[1,2-c

• ]quinazoline (8) [26], was also used in which the carbonyl oxygen at position 6 is replaced by a methyl group. Substitution at position C6 will enable to investigate the influence of electronic and steric changes for target affinity, while retaining the key pharmacophoric features of the indoloquinazolinone

• . Comparative analysis of the most active derivative 9c (Table 2) with its structural analogue 10b (Table 3) revealed that replacing the carbonyl group with a methyl moiety appears to increase the non-specific cytotoxicity of this chemotype, thereby reducing its selectivity. We also estimated the potency of the

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• sufficiently electrophilic carbonyl carbon atom with the elimination of triphenylphosphine oxide via the aza-Wittig reaction. It should be noted that the best method for the isolation of quinoxalinones 9 was column chromatography using an elution gradient of hexane/ethyl acetate 3:1 to hexane/ethyl acetate 1:2

• shift of the signal in the 198 ppm region, corresponding to the carbonyl carbon of compounds 8, to a stronger field in quinoxalinones 9, where cyclization of the keto group has occurred. The structure of quinoxalinones of type 9 was finally assigned based on X-ray diffraction analysis made for 3-(4-(2

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• transformations of carbonyl substrates with umpolung processes of aldehydes such as the benzoin condensation and Stetter reaction being particularly well studied [4][5][6][7][8][9][10][11]. In these processes, addition of the NHC to the aldehyde followed by proton transfer generates the enamine-like Breslow

• intermediate A (Figure 1a), in which the formerly electrophilic carbonyl carbon reacts as a nucleophilic center. In this way, the traditional reactivity profile of the carbonyl group is transiently inverted, and unconventional product classes are generated. Alternatively, addition/elimination of the NHC to a

• species C benefitting from additional stabilization by virtue of electron delocalization onto the NHC-derived azolium ring [17][18][19][20]. Similarly, the cationic azolium fragment in acylazolium salts can effectively lower the carbonyl reduction potential relative to the starting material with single

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

• intermediate 22 (see Supporting Information File 1 for the details). Reasoning that the preferential coordination of the palladium catalyst with the hydroxy group at C15 and the carbonyl group at C18 in compound 22 may have deactivated the palladium catalyst [34], we protected the hydroxy group. Compound 22

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

• stereoisomer has the ring-junction NC–H bond, the imide carbonyls, and the oxindole carbonyl all cis to one another across the two newly formed rings. This must arise from a preference for an exo transition state that places the incoming maleimide away from the oxindole carbonyl. The cascade chemistry allows

• same stereochemical outcome predominates. There are two possible exo transition states, both of which avoid steric (and electronic clash) of the dipolarophile carbonyls with the oxindole. Of these, the preference appears to be for the dipolarophile carbonyl groups, in this case for dimethyl maleate, to

• approach the nitrone on the side opposite the oxindole carbonyl (in a similar way to that shown in Figure 2 for the maleimide). Conclusion In conclusion, we have demonstrated the feasibility of our approach to the core of several Alstonia alkaloids by using a cascade cyclisation–dipolar cycloaddition

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• of carbonyl compounds, such as aldehydes or ketones, with active methylene compounds [37]. The resulting α,β-unsaturated carbonyl products can then be further elaborated to form natural products, therapeutic agents, polymers, pesticides, and insecticides [38], which have important applications in the

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

•  14, box) and repulsion between the aryl and the carbonyl group in the E-isomer. Some studies on N-acylindigo derivatives reported, besides the expected spectral blue-shift, also a decrease in the fatigue resistance due to photochemical rearrangements [68][69]. Dube and co-workers reported a series of

• interesting results: in the case of derivative 63 containing pyrrole, capable of hydrogen bonding with the carbonyl oxygen (Scheme 20, left) [61][62], the E form is obtained almost quantitatively upon irradiation. In the case of pyridine-containing derivative 64 (Scheme 20, right) no photoswitching is

• pronounced red-shift of the E-isomer was observed for the pyrrole derivative 66 [81], showing that the hydrogen bond between pyrrole and carbonyl also plays a role (Scheme 21, left). The band separation also provides almost quantitative PSS in both directions. The imidazole derivative 67 (Scheme 21, right

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

• promising industrial relevance. Oxidative cleavage of alkenes to yield carbonyl compounds is one of the key transformations in synthetic organic chemistry [41][42]. Over the past two decades, this field has witnessed significant advancements, primarily through the use of organic oxidants and transition

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• through a σ-type intermolecular halogen bonding (C–Br···O) between the ortho-bromine atom and the carbonyl oxygen. The formation of similar heterochiral polymers through a σ-type intermolecular halogen bond (C–Br···S) was also found in crystals of the thio-analogue rac-II. On the other hand, in the