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

• observed differences in the EC50 values between the same structures 3 and 4, except 4 is the methyl ester of 3. Conclusion In this study, we isolated four compounds, two previously undescribed as natural products (1 and 2) and two new compounds (3 and 4) from Pseudomonas sp. UIAU-6B cultured in SGG liquid

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

• discussed in more detail and illustrated by specific examples. 1.1 C–O bond-forming cyclisations 1.1.1 Intramolecular Williamson etherifications: Discovered by Alexander Williamson in 1850, this reaction is an SN2 substitution in which a leaving group, typically a halide or sulphonate ester, is displaced by

• ) [78]. Initially, racemic 2-bromo-γ-butyrolactone (114) was contracted by ethanolic KOH into oxetanecarboxylic acid, which was then esterified and the enantiomeric ethyl esters were resolved by an enzymatic hydrolysis. Finally, the enantioenriched ester 115 was successfully employed in several multi

• , the synthesis starts with the preparation of a reactive amine species 170 which is then reacted with a Grignard or, in case of ester-containing substrates, with an organozinc reagent. Because this method involves only two simple steps and is not limited to aryl groups, it provides a more rapid access

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

• synthetic strategy. The tandem Suzuki coupling/Knoevenagel condensation strategy leading to PAH 85 was independently reported by Liu [61] and Mastalerz (Scheme 12) [62]. The first group reported a cascade formal [3 + 4] annulation between triple boronic ester 83 and naphthalene 84 which combines a Suzuki

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

• methoxy (-OMe) and halogens (-F, -Cl, -Br), as well as electron-withdrawing functionalities like trifluoromethyl (-CF₃) and ester groups (-CO₂Me). However, highly electron-deficient substrates, such as those bearing cyano (-CN) or nitro (-NO₂) groups, did not react. Additionally, the study explored

• –c) and electron-withdrawing (e.g., fluorine, chlorine, ester groups) (78d–f) substituents on bromodifluoroacetamides were well tolerated, yielding high reaction efficiency. Interestingly, the reaction was less sensitive to electronic effects on the aromatic ring, as yields remained high regardless

• substituents on the aromatic ring (79a–d). Functional groups such as hydroxy, ester, and lactam were tolerated, demonstrating the method’s broad applicability (79e–g). However, strongly electron-withdrawing substituents, such as nitro and cyano groups (79h,i), failed to undergo the reaction, likely due to the

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• presumed byproducts in the addition–elimination sequence in the presence of an excess of ethanol as a cosolvent are the ethyl ester formed by Einhorn acylation [7] of the acid chloride under the standard conditions and deep colored polar byproducts (according to TLC detection) that arise from self

• dichloromethane; N = 17.10 in acetonitrile) [14] than ethanol or the S,N-ketene acetal intermediate 4. Hence, mechanistically the acid chloride first transforms to an acylammonium species as in Einhorn acylations [7]. As a consequence, for avoiding any competing ethyl ester formation, ethanol has to be omitted

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

• . Intermediate 25 was prepared through TBDMS protection and desulfonylation of 24, itself derived from the condensation of epoxide 23b and sulfone 27. The precursor 27 was synthesized from Roche ester 29 via a sequence of steps, including reduction, three-carbon homologation, and enzymatic desymmetrization. An

• % yield over three steps. This compound was isolated in its pure form as a white solid after recrystallization from ethanol, confirmed by HPLC and NMR. In parallel, the primary alcohol group of ent-38 was protected as a TBDMS ether, and the acetate group was converted to a tosyl ester by hydrolyzing the

• reduced with LiAlH4 to remove the OTs group, and after silyl group removal, diol 32b was obtained in 92% yield. Protection of the primary alcohol as a tosyl ester and the secondary as a TBDMS ether afforded intermediate 32c (72%). This intermediate was then treated with sodium thiophenol in ethanol

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

• performance to Cs2CO3 including the lack of methyl ester hydrolysis, but a lower price. The catalyst's performance had a more significant influence on the reaction results than the base. Both phosphine catalysts as well as the second generation of the Buchwald–Hartwig catalyst [47][48] gave similar results

• well as an axial position for the methyl ester at C2. All spectra of the stereoisomer (2R,6S)-9 contain signals for a second data set. This phenomenon might be associated with cis-/trans-isomerism around the formamide bond. Maison et al. noted that a phenyl substituent at C6 of N-acyl pipecolic acid

• in the amide bond and their resulting restraints. The coupling patterns of H2 and H6 do not change upon hydrolysis of the methyl ester, resulting in product (2R,6S)-10, where the second set of signals still remains (Figure 2b). However, cleaving the formyl group, on the other hand, leads to product

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• conformation II projected only two vertically. One benzyl ring is pointed outside as highlighted by * (top). Oxygen, nitrogen, and iodine atoms are denoted by red, light blue, and purple color, respectively. A) Chemical structure of HIM 1: Three iodine atoms and three inward projected ester carbonyls

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• cinnamic acid (7) in a deep eutectic solvent of choline chloride/urea (ChCl/urea) to give amides 12 and 13 in moderate yields via triacylated triazine 14 as the active ester (Scheme 5A) [36]. The TCT reagent and ChCl/urea solvent are known for their non-toxicity and low cost, promoting their wide

• the electrophilic triazinedione, releasing DMAP to give ester 15 which reacts with DMAP to afford the active N-acylpyridinium species 16. In addition, N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC·HCl), a common coupling reagent, has been applied for a continuous flow

• amidation in 5 min reaction time via the formation of the isolable enol ester intermediate 23 (Scheme 8A). Similarly, Feng and co-workers (2019) studied one-pot two-step esterification of cinnamic acid (7) by applying electrophilic sp carbon center of methyl propiolate (25) as the coupling reagent via in

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• proceeded when DMF was used (Table 1, entry 11). The reaction in PhCF3 afforded the target product in a good yield with the highest enantioselectivity compared to other solvents (Table 1, entry 12). Furthermore, when (E)-1,3-diphenyl-2-propenyl pivalate (14) was tested as the allyl ester, the desired

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

• annulation and applied it in the divergent total synthesis of Cephalotaxus alkaloids (Scheme 3) [22], including cephalotaxine whose ester, homoharringtonine, has been listed as an approved FDA drug for the treatment of chronic myeloid leukemia [23]. In their elegant study, an Au-catalyzed [2 + 3] annulation

• was utilized to transform enamine 18 and propargyl ester 19 into 1-azaspiro[4.4]nonane 20 with high diastereoselectivity. Notably, the combination of an N-heterocyclic carbene gold catalyst and a silver salt AgSbF6 was found to be essential in guaranteeing the reactivity of the alkyne partner

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• ester 29 gave pyrrolo-β-carboline 30 in excellent yield (Scheme 7). Our attempts for the selective saturation of the pyrrole ring of 30 by catalytic reduction were unsuccessful. When the hydrogenation was carried out under mild conditions (ambient temperature, 15 bar H2) in the presence of PtO2.H2O

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

• 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

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

• hydrogen atom transfer (HAT)/chiral copper dual catalytic system that achieved regiodivergent and enantioselective C(sp3)–C(sp3) and C(sp3)–N oxidative cross-couplings between N-arylglycine ester/amide derivatives and abundant hydrocarbon C(sp3)–H feedstocks (Scheme 6) [24]. This methodology also

• represents a highly challenging direct C(sp3)–H asymmetric amination. Mechanistic insights: When using a bulky, electron-rich chiral bisphosphine ligand L6, the glycine ester substrate coordinates with the copper catalyst to form a key intermediate complex Int-26. The sterically hindered and electron-rich

• the anionic cyano-substituted bisoxazoline ligand L7, the glycine ester and copper catalyst form a distinct intermediate complex Int-28. The ligand’s reduced steric bulk and altered electronic properties facilitate direct interaction with alkyl radicals, forming a high-valent Cu(III) intermediate Int

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• bearing aromatic and aliphatic substituents efficiently provided the allylboration product (Scheme 1a), the use of ester derivative 1 under same reaction conditions led to the formation of an unexpected product arising from the coupling of two dichloride molecules with no alkyne incorporation (Scheme 1b

• ). We have studied this reaction and now report a catalytic methodology for the diastereoselective synthesis of these dimeric structures. The high degree of functionalization present in these molecules, which feature two ester groups, an aliphatic gem-dichloride and a dichloroalkene unit, offers ample

• the copper–boron bond into 1. The dual functionality of this substrate imposed a question related to the regioselectivity of the Cu–Bpin insertion since it can potentially behave as an α,β-unsaturated ester or an allylic substrate [16][17][18][19]. To shed some light into this issue, we ran the

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• + 2] cycloaddition established, the scope and pivotal properties of the core structure was assessed (Scheme 1). Single point modifications of the tethered backbone were tolerated, enabling access to small 3D bicyclic scaffolds 4b, 4c, and 4d containing both a boron and ester handle. Consciously aware

• that α,β-unsaturated esters could potentially also undergo energy transfer in the presence of high energy sensitizers [59][60], the system 4e with two ester components was also designed. The reaction proceeded cleanly to the cycloadduct, indicating sensitization of the acrylate is also operational

• more efficiently sensitized (lower T1 excited state) than their alkenylboronic ester counterparts. This is unsurprising given their enhanced conjugation (4π electrons vs 2π electrons and p-orbital). To probe the efficiency of trisubstituted alkenes, vicinal boron precursor 3h was designed (Scheme 1

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• reaction occurred at the ortho position relative to the ester group. Also, after a few hours, the reaction yield decreased when the reactants were pre-mixed with HBF4. A series of analyses revealed that P(OEt)3 decomposes into various phosphorus species without H2O. Additionally, the studies showed that P

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• demonstrated excellent compatibility with the protocol, affording the desired products 3ba–ea in good yields. However, the introduction of strong electron-withdrawing groups, such as trifluoromethoxy, ester, and acetyl, at the para-position of the benzene ring (1f–h) led to a noticeable decrease in the yields

• to be compatible substrates, affording cyclo-O/S-containing STHQ derivatives 3ab and 3ac in good yields. Additionally, ester-functionalized cyclobutanones exhibited smooth reactivity with aniline, enabling the synthesis of substituted STHQ motifs 3ad and 3ae in satisfactory yields. Notably, when

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• ., to generate an ester), the gauche O–C–C–F conformation is favoured over anti more strongly than was seen for the parent alcohol (e.g., energy difference between gauche and anti = 1.0 kcal·mol−1 for esters; 0.3 kcal·mol−1 for alcohols) [109]. This is likely due to enhanced hyperconjugation effects in

• the ester case (i.e., σC–H → σ*C–F and σC–H → σ*C–O, III, Figure 8). Examples of this phenomenon are seen in the crystal structures of compounds 59 and 60 (Figure 8), which are synthetic precursors of β-fluorinated amphetamines; both of 59 and 60 feature a gauche O–C–C–F alignment regardless of other

• that features both an ester moiety and an amino group will be discussed later, in section 5 of this review [112]. 4 Sugars We have examined several classes of molecules of gradually increasing complexity, progressing from alkanes (section 1) to ethers (section 2) and then alcohols (section 3

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• electronegativity, reaching 1.648 Å in the reactive alkoxytrialkyl complex D and 1.659 Å in the tetraalkyl "ate" complex E. The B–C bond lengths in amido- and alkyl-substituted boronic ester complexes B and C fell between these extremes, suggesting an intermediate level of activation. These findings prompted

• metathesis with HBpin to afford a vinylboronic ester intermediate 45 alongside the regenerated L*CuH catalyst, completing the first catalytic cycle. Subsequently, a ligand-controlled regioselective migratory insertion of L*CuH into the vinylboronic ester 18 delivers the corresponding chiral alkylcopper

• -diborylalkanes 47 using an H8-BINOL-derived phosphoramidite ligand L5, achieving exceptional enantiocontrol (Scheme 16) [59]. Their studies revealed the critical role of both the alkali metal cation and boronic ester moiety. While LiOt-Bu provided excellent enantioselectivity (er = 95:5), NaOt-Bu and KOt-Bu

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

• , NaOAc) did not improve the efficiency of the anodic decarboxylation/cyclization reaction (Table 1, entries 2–4). Even though the amount of hemiaminal 10a was slightly reduced, the formation of amino acid ester 11a as side product was observed in the crude reaction mixture (Table 1, entries 2–4). The

• NMR methods, and all attempts to obtain crystals suitable for X-ray crystallographic analysis were unsuccessful. N-Protected 2-aminoproline derivatives 6 are relatively stable under basic conditions as evidenced by successful hydrolysis of the ester moiety in 6a,d,e using aqueous LiOH to provide acids

• 13a,d,e in 71–83% yield (Scheme 4). Carboxylic acid 13a could be reacted with glycine benzyl ester in the presence of HATU and Et3N to form dipeptide 16 (66%). In contrast, N-unprotected 2-aminoprolines are unstable and could not be isolated. Thus, the cleavage of the N-Cbz protecting group in 6b

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• -carbonyl group was linked through an ester bond and the only hydroxy group available for this esterification was the one at C-7. This compound was finally elucidated as massarilactone D 3,4-di-O-methacryloyl-7-O-(6-chloro-3,4-dihydro-2,5-dimethyl-2H-pyran-2-carbonyl). For the formation of compound 2, an

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

• that the isocyanide component decomposes to an arylimine, which undergoes a cycloaddition with another isocyanide molecule to this byproduct. However, if an amino acid is exchanged for an amino ester, the reaction affords the corresponding product 43e (Scheme 40) as an amino acid derivative

• . Application of glyoxylate derivatives in post-cyclization reactions as a C1 building block Glyoxylate derivatives have been used in Ugi- and Passerini-type reactions, since the adduct generated in both cases has two reactive centers for post-cyclization possibilities: the ester moiety and the α-carbon to the

• peptide carbonyl group. Both moieties result from the glyoxylate compound (Scheme 43). There are many examples in which the ester moiety opens the possibility of a further intramolecular cyclization with a nucleophile (for example, a protected amine in an Ugi/deprotection/cyclization sequence [98][99][100

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• tetrasubstituted carbon stereogenic centers [42][43][44][45][46]. In 2011, Shibasaki, Matsunaga and co-workers reported strontium or magnesium-catalyzed stereodivergent asymmetric Mannich reactions of an α-isothiocyanato ester with ketimines, which provided the products in excellent yields and

• reaction; the stereoselectivity of product 17j drastically dropped. The scope for the pre-nucleophile showed that phenyl-substituted 16b provided 17k in 94% yield with high diastereoselectivity, albeit with decreased enantioselectivities. Methyl ester 16c and tert-butyl ester 16d were also applied to the

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• in water [21]. Crown ether 1 is particularly suited for the sensing of Trp methyl ester, which it binds with a higher affinity than the Phe and Tyr esters. Additionally, the binding of Trp-OMe results in a highly efficient fluorescence quenching of the naphthalene unit in the receptor. Herein, we

• report that receptor 1 can be used for the binding and fluorescent sensing of tryptophan as well as tryptophan residues in short peptides in water. Results and Discussion Having previously demonstrated that 1 binds tryptophan methyl ester in water [21] we wanted to investigate whether it is also suitable