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

• DCC-induced condensation of phenylacetic acid reported by Bhandari and Ray [22] and others [23][24][25][26][27]. Initially, we converted indole-3-acetic acid to its methyl ester, followed by protection of the indole nitrogen with a Boc group and subsequent hydrolysis of the methyl ester to regenerate

• to form a tert-butyl ester, leading to unwanted side products and reduced selectivity. Once the acid was protected, the Boc group could be selectively introduced onto the indole nitrogen without side reactions. Overall, this sequence ensured clean N-Boc protection with minimal side reactions and

• methyl ester as a brown oil (5.1 g, 94%); Rf = 0.3 (EtOAc/hexane 1:2). Spectroscopic data for the methyl ester agreed with those in the literature [31]. The methyl ester (5.0 g, 26.0 mmol, 1.0 equiv) was then dissolved in acetonitrile (25 mL) and di-tert-butyl dicarbonate (17.0 g, 78 mmol, 3.0 equiv) and

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

• work, based on the large conformational freedom that is given by the long, flexible linkers [51]. To achieve a convergent synthesis, we first designed the hexaethylene glycol linker 96, which features a tosylate leaving group at one end and a phenylboronic ester at the other end (see Figure 5). This

• routes towards macrocycles featuring one BINOL unit. a) Two-fold Suzuki coupling and b) two-fold Williamson synthesis. Reagents and conditions: i) bis(boronic ester) 75/6/7/8 (1.0. equiv), Pd2(dba)3 (0.1 equiv), P(o-Tol)3 (0.2 equiv), n-Bu4N+OH− (3.2. equiv), toluene/H2O 5:1, 90 °C; ii) ethylene glycol

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• (Scheme 2). Switching from “disarming” ester to “arming” benzyl protecting groups, as in the donor 21, enhanced the activation of the glycosidic center, resulting in the formation of a substantial amount of the methyl glycoside by-product and a reduced yield of the 1,1'-disaccharide 22. Securing the

• the formation of a borate complex [61]. Diarylborinic acids have also been exploited for stereoselective 1,1'-glycosylations through the formation of a 1-O-monoborinate ester, resulting from the complexation of a 1,2-dihydroxyglycosyl acceptor with a diarylborinic acid derivative. Concurrent

• variable ether- and ester-type protecting groups on the other, were obtained in yields of 64% and 72%, respectively (Scheme 9). Synthesis of aminosugar-containing nonreducing disaccharides proved being more challenging, as demonstrated by the use of 2-azido-2-deoxy 1-O-TMS-glycoside 105 as acceptor [71

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• . Moreover, an axially chiral tertiary alcohol-phosphine 42 was prepared from 39a through a three-step procedure including N-methylation, reduction of phosphine oxide, and Grignard addition to ester. Subsequently, 42 was applied as a bifunctional Lewis base organocatalyst in the formal [4 + 2] cyclization

• with high enantioselectivities. In terms of isocyanides, isocyanoacetates with different ester groups, p-toluenesulfonylmethyl isocyanide (47e), and isocyanoacetamide (47f), were all compatible. It is noteworthy that this work represents the first example of catalytic asymmetric DKR of Bringmann’s

• with both axial and central chirality, followed by 2) ring-strain and aromatization-driven elimination, which elucidating the observed unusual torsional strain-independent reactivity. In addition, products bearing a tert-butyl ester group were smoothly converted into structurally novel axially chiral

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

• group in compound 10. Compound 10 can be realized by introducing an ester group in 9, which is the [3 + 2 + 1] cycloadduct from 8 and CO using a Rh catalyst. The [3 + 2 + 1] substrate of yne-vinylcyclopropane (yne-VCP) 8 can be synthesized by Wittig reaction from cyclopropyl aldehyde 7, in which the

• introduce an ester group at the α position of the carbonyl group in 9 to get compound 10, which could have a more nucleophilic carbon better for the Heck reaction. 10 was obtained in 70% yield with a diastereomeric ratio of 4.5:1. Then, we screened various palladium catalysts and solvents to accomplish the

• . 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

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• ester group. In our case, the demethoxycarbonylative annulation enables the formation of aromatic tricyclic benzo[4,5]thieno[3,2-b]pyrrole system which is encountered in compounds with antitumor activity [21][22] as well as in compounds exhibiting fluorescent properties [22][23]. Since general methods

• under the Vilsmeier–Haack reaction conditions provided aldehyde 8 in high yield. To further assess the scope and limitations of the developed annulation protocol, we investigated the reactivity of aza-analogs of ester 1, indoles 9a‒c, toward azirine 2a under the same conditions. The reaction of N

• [4]. Conclusion In summary, a protocol for the efficient construction of the benzo[4,5]thieno[3,2-b]pyrrole skeleton by the annulation reaction of the aromatic system, 3-hydroxybenzo[b]thiophene-3-carboxylic ester, with 3-arylazirines has been developed. The annulation is catalyzed by Ni(hfacac)2 and

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• precursors 4a–c were then prepared by the reaction of compounds 3a–c with N-chlorosuccinimide (NCS) in dimethylformamide (DMF). The ester group-containing chloro oxime 4d was obtained by the treatment of glycine ethyl ester hydrochloride with sodium nitrite and hydrochloric acid [25] and used thereafter as

• for compounds 5a–l. However, in most cases, this method is more laborious due to the similarity in the retention factor values of the initial imines 2 and the reaction products. In this way, products 5i and 5j with good solubility in diethyl ester were isolated. A comparative analysis of compounds 5a

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• amounts of 1–5 wt %. Keywords: biodiesel; calcium oxide; carbide slag; ester; transesterification; Introduction The ester moiety in molecules is one of the most important functional groups, which is widespread in nature, products of fine organic synthesis, and large-scale chemical manufacturing [1][2][3

• was calcined at 600 °C before use and the catalyst CS600 was characterized using XRD and FTIR analysis, confirming the presence of CaO as the main phase. The primary alcohols successfully reacted in the transesterification reaction to give the corresponding fatty acid alkyl ester mixtures in yields

• used in the transesterification of soybean oil with methanol and the yield of fatty acid methyl ester mixture was 99% (Table 1, entry 1). Soybean oil was chosen as a model triglyceride composed of fatty acid residues as a mixture of palmitic acid (14.7%), stearic acid (3.6%), elaidic acid (24.5%), and

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

• ). Notably, when chalcogen-containing substrates were used, the process afforded phosphorus ester derivatives of aza[5]helicenes. The chiral nature of the products was confirmed by optical rotation and CD measurements. In parallel, Soni’s group established an efficient three-step synthesis of coumarin

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