Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• . Additionally, a new absorption band at 1558 cm−1 was observed in the spectra of SG-NHCO-BU1 further confirming covalent attachment of BU1 through an amide bond. In the case of SG-BU1, a C=O vibrational band is observed at 1705 cm−1, which corresponds to the vibration of the C=O of BU1 carboxylic acid groups

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

• rearrangement of 28 enabled the rearrangement of cis-pentalene to trans-pentalene, delivering intermediate 29, which possesses the same carbon skeleton as the natural product. Further oxidation of the primary alcohol to a carboxylic acid, accompanied by TBS deprotection, afforded hemiketal 30. Finally, a White

• protected prior to the RCM step. Oxidative cleavage of the cyclopentene followed by Pinnick oxidation of the resulting aldehyde to the carboxylic acid and esterification yielded ketoester 56. Dieckmann condensation of 56, esterification of the resulting enolate with 57, and subsequent one-pot partial

• , generating an allylic alcohol that was acetylated in situ to provide 74. An Ireland–Claisen rearrangement facilitated the third olefin transposition, concurrently forming an all-carbon quaternary center at C9 and affording carboxylic acid 75. The fourth olefin transposition was achieved via a palladium

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

• deprotection and ester hydrolysis produced carboxylic acid 101, which upon oxidative dearomatization yielded dienone 102, thus completing the D-ring. Regioselective epoxidation to 103 and reduction (using Adams' catalyst) through intermediate 104 gave lactone 105. A retro-oxa-Michael/intramolecular

• , provided carboxylic acid 113 in a single operation. Subsequent activation of 113 with acetic anhydride, relactonization, and organoselenium-mediated regioselective epoxide opening yielded mono-enone 114, successfully installing the key C9 and C10 chiral centers with the required oxidation states. Notably

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

• incomplete conversion resulted in Boc protected beta-alanine that was challenging to separate from the desired product (3). Carboxylic acid 3 then underwent a peptide coupling reaction with allyl-protected PNA backbone 4 to afford nitrobenzene 5 in 69% yield. Nitrobenzene 5 was then reduced to the

• synthesis of aniline 10 and carboxylic acid 13. To access 10, the isoorotic acid derivative 6 was treated with oxalyl chloride to form the corresponding acyl chloride in situ which was then slowly added to a solution of m-phenylenediamine (9) to afford the target aniline in 62% yield (Scheme 2). Slow

• addition of the acyl chloride to excess 9 was important to avoid forming bis-acylation of the phenylenediamine. The carboxylic acid 13 was formed using a microwave-promoted ring opening of glutaric anhydride (11) and benzyl-protected PNA backbone 12 [38]. A series of optimizations was performed in a

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• formation of carboxylic acid 9bA, isolated in 71% yield (Scheme 7). In addition, an attempt to cyclize 6b in the presence of DBU without a solvent at 110 °C led to significant destruction of the substrate and product 9b was obtained with a yield of about 20%. Cyclization of substrate 4a with NaH in toluene

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

• this key intermediate in hand, β-hydroxy acid 29 was synthesized through deprotection, IBX oxidation, and Pinnick–Lindgren–Kraus oxidation and the β-lactone 13 was subsequently obtained through activation of the carboxylic acid. Although we successfully constructed the molecular scaffold of

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• following: a mixture 3-functionalized indole 19 (0.08 mmol), 2-alkynylaniline 20 (0.12 mmol), (R)-Rh1 (5 mol %), n-Bu4NOAc (0.08 mmol), 1-adamantane carboxylic acid (1-AdCO2H, 0.08 mmol) and MeOH/CHCl3 (1:1, 2 mL), under electrolysis (graphite felt (GF) anode and graphite (C) cathode, 2 mA, 5.6 F/mol) at rt

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

• ligand led to excellent enantioselective induction during the hydrogenation step. Higher H2 pressure could promote the regeneration of Cu–H species [214]. Levulinic acid (LEV) Levulinic acid is a biodegradable C5 carboxylic acid with high potential as a platform chemical in the field of polymers, fuels

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

• give (15R)-110 and (15S)-110 in 65% and 54% yield, respectively. Subsequently, ten functional group manipulations of the diastereomeric mixture 110 produced ketoester 111. Finally, the introduction of conjugated double bond in 111 followed by hydrolysis of the methyl ester to carboxylic acid and DCC

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• between an aldehyde, an amine, a carboxylic acid, and an isonitrile in 1959 [8], which marked the beginning of modern MCR chemistry, continues to attract undiminished attention. It has since been applied in manifold ways, from breathtaking reaction sequences and post-Ugi transformations to the generation

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

• introduce the carboxylic acid group a sequence of formylation/oxidation reactions was used. Vilsmeier–Haack reaction of 1 afforded 6-oxoindolo[1,2-c]quinazoline-12-carbaldehyde (2) (Scheme 1). All attempts to oxidize the aldehyde group of 2 to the corresponding carboxylic acid were hampered by the oxidative

• sensitivity of the indole moiety, resulting in poor selectivity and formation of complex product mixtures. In particular, Jones oxidation of 2 gave the corresponding 6-oxoindolo[1,2-c]quinazoline-12-carboxylic acid (3) in a low yield (Scheme 1) making it necessary to look another synthetic pathway. Of

• (5) (Scheme 1), a structural analogue of the biologically active alkaloid tryptanthrin (Figure 1). An alternative scheme to indolo[1,2-c]quinazoline-12-carboxylic acid (3) was based on initial acylation followed by a haloform reaction. Refluxing compound 1 with trifluoroacetic anhydride (TFAA) in

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• acid, its sodium salt or the silylated carboxylic acid), the arylation reaction of aliphatic chain-containing propargylsilane 7b (standard conditions; see Scheme 3) only resulted in the arylation of the oxygen nucleophile itself. Next, we proceeded to expand the substrate scope by exploring other

• internal nucleophiles (Scheme 4), that could be used instead of the alcohol. The carboxylic acid-containing silane 7 (R = COOH), which was obtained by stepwise oxidation of the alcohol 7d, failed to give the desired lactone 8t product due to O-arylation of the carboxylic acid, leading to phenyl alkyl ester

• described by us recently, among other possible transformations [21][22]. Interestingly, the addition of O-nucleophiles to form 1,3-carbofunctionalization products, can only be achieved in an intramolecular fashion. In the presence of an excess (5 equiv) of external an O-nucleophile R–OX (alcohol, carboxylic

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

• suitably electrophilic substrate at the carboxylic acid oxidation level provides an acylazolium species B, which typically reacts directly with nucleophiles or may first be transformed into the corresponding enolate derivative. Regardless of the individual pathway, NHC-catalyzed reactions of this type

• manifold with carboxylic acid derivatives, numerous coupling processes affording ketone products have been developed. Since the initial report from Scheidt and co-workers using 4-alkyl-substituted Hantzsch esters as coupling partners [31][32][33][34][35][36], several alkyl radical sources have been

• contrast to these numerous reports with carbon-based alkyl radicals, dual NHC/photoredox-mediated coupling processes between carboxylic acid derivatives and other classes of radical are lacking [22][23][24][25][26][27][28][29][30]. In particular, to the best of our knowledge, formal reduction reactions of

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

• . Epoxidation of 131 followed by methylation generated epoxide 132. Construction of the lactone moiety commenced with the oxidative cleavage of the double bond, and the resulting carboxylic acid underwent intramolecular cyclization in the presence of BF3·Et2O to give lactone 133. Subsequent hydride reduction

• ) was prepared by methylation of 262 with MeI, while (+)-polyneuridine aldehyde (264) was synthesized directly from alcohol 262 via Corey–Kim oxidation. The Trauner group also employed a similar strategy in the synthesis of stephadiamine in 2018 (Scheme 32) [80]. Starting from carboxylic acid 265

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• asymmetric synthesis of planarly chiral macrocyclic paracyclophane 47 from the corresponding hydroxy-substituted carboxylic acid substrate 46. Notably, the authors also demonstrated the application of this method in the enantioselective synthesis of axially chiral C–N and N–N atropisomers, highlighting the

• , resulting in kinetic resolution with an exceptional performance. In 2025, Zhou and co-workers disclosed the asymmetric synthesis of planarly chiral macrocycles via CPA-catalyzed atroposelective macrocyclization [42]. The authors devised and prepared a series of indole-based hydroxy-substituted carboxylic

• acid substrates 43 which, upon treatment with ynamide 44, yielded the vinyl acetate intermediate INT-A (Scheme 13). Subsequently, the one-pot CPA-catalyzed intramolecular esterification of this intermediate afforded the planarly chiral macrocycles 45 with good yield and high enantioselectivity

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

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

• ]arene (WP7) by adding 14 anionic carboxylic acid groups to both sides [102]. They explored the pH-dependent complexation of WP7 with paraquat derivative G1 in water. The host WP7 and guest G1 form a 1:1 pseudorotaxane, with an association constant of (2.96 ± 0.31) × 105 M−1. Furthermore, they leveraged

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

• the carboxylic acid (Scheme 1B) in a manner similar to that described by Knör et al. [28]. Protection of the carboxylic acid group prior to conducting the N-Boc protection with di-tert-butyl dicarbonate ((Boc)2O) and DMAP was required to avoid competitive reaction of the carboxylic acid with (Boc)2O

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

• . Unfortunately, failure was encountered here. This can be expected because the reaction site here is a bridge quaternary center (no such example was reported in literature for this) [31][32][33]. Due to this, we then converted the ester group in 12 into a carboxylic acid group, reaching 13 in 72% yield. Finally

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• show modest activity against L. major. All the remaining compounds (1–3 and 5–7) tested in this assay showed no activity at the highest concentration very likely due to the free carboxylic acid moiety present in some compounds (1, 3 and 7), prevent uptake into the parasites. This could also explain the

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

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

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

• and carboxylic acid. The palladacycle intermediate can undergo further (coupling) reactions and form a variety of products via reductive elimination. In previous studies, the rate- and regioselectivity-controlling step was identified as the formation of the palladacycle [5][6][7]. The regioselectivity

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

• the correct stereochemistry of the newly formed three stereocenters. Additionally, replacing cesium carbonate with triethylamine proved crucial for achieving efficient asymmetric hydrogenation in this case. Subsequently, the carboxylic acid group of 57 was reduced with LiAlH4 in THF to produce primary

• %), followed by protection of the secondary alcohol as TBDMS ether 81 (98%). The primary alcohol was then liberated using ammonium fluoride in hot methanol (60 °C). Oxidation of this alcohol to a carboxylic acid was achieved using TEMPO and (diacetoxyiodo)benzene (BAIB), completing the synthesis of the target

• treatment with Ph3P/I2/imidazole reagents and reacted with lithiated pseudoephedrine propionamide. The resulting product 144 was obtained in 88% yield. Basic hydrolysis of this compound successfully removed the chiral auxiliary, yielding acid 145 in 91% yield. Sequential reduction of this carboxylic acid

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

• acid (7-ACA) from cephalosporin C by cephalosporin C acylase [37], was used as a chiral starting material. After esterification of both carboxylic acid functions followed by cyclization to the lactam [38][39], the six-membered ring structure was established as (R)-methyl 6-oxopipecolate (7) with a high