Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• reduction of ketone using SmI2 and propionaldehyde provided 15 diastereoselectively. Friedel–Crafts cyclization using trimethyl orthoformate and TMSOTf provided the cyclic acetal moiety to be oxidized with PDC, delivering the isocoumarin skeleton in 16. Chemoselective removal of the ester with the lactone

• underwent dehydroxylation protocol involving base-promoted mesylate elimination and catalytic hydrogenation reactions, providing 31a. Reduction of lactam and ester in one pot with LiAlH4 and acid-promoted hydrolysis of ketal protection to ketone furnished 32a. Finally, oxidation of the primary alcohol to

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

• reaction [17] and a [4 + 2] annulation reaction between o-carboxylic ester-containing diaryl-λ3-iodanes and some terminal alkynes [18]. Looking to expand the possibilities for terminal alkyne carbofunctionalization, we turned our attention to propargylsilanes, which are prone to undergo cationic

• 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

• formation. Its silylated version (7, where R = COOSi(Me)3) only resulted in starting material degradation. Interestingly, tert-butyl ester 7e (R = COOt-Bu) provided the desired arylated lactone 8t, along with the protodecupration product 13, which was formed in excess under the standard arylation conditions

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

• offer many synthetic advantages while the wide availability of chiral NHCs can also allow for high levels of enantioselectivity. As effective enamine and active ester derivatives, Breslow and acylazolium intermediates A and B typically react via classical two-electron polar mechanisms, however, recent

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

• pathophysiological mediator in many human diseases and biological pathways. Tricyclic prostaglandin D2 metabolite methyl ester (tricyclic-PGDM methyl ester), the major urinary metabolite of PGD2, can be used as a clinical indicator for PGD2 overproduction. However, the limited amount of tricyclic-PGDM methyl ester

• available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total

• 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

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

• 25 with vinyl butanoate and PPL delivered monoester 26 in 92% yield (99% ee). The axial chirality was transferred to the C7’ stereocenter through a Ag(I)-catalyzed cycloisomerization of the allenol, constructing the dihydrofuran ring. Lipase-catalyzed ester hydrolysis provided allylic alcohol 27

• sequence comprising TBS protection, ester hydrolysis, mesylation, and hydride reduction. In 2014, Tokuyama and co-workers accomplished the total synthesis of (−)-petrosin and (+)-petrosin, two marine-derived bisquinolizidine alkaloids [45]. They first completed the synthesis of (−)-petrosin (84) (Scheme

• with 99% ee. The TBS protection was crucial to prevent the potential racemization by intramolecular transesterification. Ester 79 was then prepared from 78 in eight steps. To complete the dimerization, fragments 80 and 81 were independently prepared from 79. An intermolecular Suzuki–Miyaura coupling

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• agent; glycidyl ester; electrochemical evaluation; phosphorus-containing drug; Introduction Phosphorus-containing drugs represent a crucial category of therapeutic agents, extensively utilized in clinical practice due to their diverse pharmacological properties and applications [1][2][3][4]. These

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

• fumarate was also successful and gave a mixture of the stereoisomeric cycloadducts 7 (Scheme 5). The yield was high and three inseparable stereoisomers could be detected by 1H NMR spectroscopy. In each case we assume that the methyl ester groups are trans to one another due to the expected concerted nature

• of the dipolar cycloaddition process. In contrast, the dipolarophile dimethyl maleate gave predominantly one stereoisomer of the cycloadduct 8 (ratio of isomers 95:5) (Scheme 5). The stereochemistry of the major isomer was assigned from NOESY analysis, that indicated the methyl ester groups were cis

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 transfer hydrogenation employing Hantzsch ester HEH-1 as the reductant afforded both helically chiral tetrahydroquinoline derivatives (M)-30 and the recovered aza[6]helicene starting material (P)-29 with good to high enantioselectivity, achieving an s-factor of up to 121 (Scheme 8). Moreover, by

• resolution or dynamic kinetic resolution [40]. The authors designed and synthesized a series of benzaldehyde-containing macrocyclic cyclophanes 38. Therein, they achieved the construction of planar chirality through CPA-catalyzed asymmetric reductive amination with arylamines using Hantzsch ester HEH-2 as

• with allylboronic acid pinacol ester (41) led to efficient kinetic resolution, yielding the recovery of (Sp)-40 with high enantiopurity (Scheme 12). Notably, the allylation products 42, possessing both planar chirality and central chirality, were produced with high enantioselectivity and

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

• with the increasing lipophilicity of the alkyl chains, which is a result of the increase in surface area of the alkyl groups [51]. Of further interest are the results of the catalysis under the same neat conditions using the dimethyl ester of our catalytically active linker, Me2-BDC-NH2 (Table S3

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

• weaken the hydrogen bonds between N–H and the ester moieties of the rotor and the stator. The Cigáň group focused on the synthesis of benzoylpyridine hydrazones with different substitutions in the rotor benzene [97]. The p-NMe2 group causes red-shift of both absorption maxima of the E- and Z-isomer

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

• composed of MSNs and choline sulfonatocalixarene[2]pseudorotaxane. Two different choline derivatives with distinct structures and lengths (Figure 14) were grafted onto the pores of MSNs via ester or urea linkages, serving as enzyme-cleavable sites. Negatively charged SC4A macrocycles were introduced to

• envelop the choline stems on the surface of MSN-NPs through host–guest interactions, forming pseudorotaxanes as the mobile/cleavable components of the nanovalves. It was experimentally demonstrated that esterase could selectively activate the ester-linked nanovalve (MSN-C1), while urease could selectively

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• amino alcohols derived from furfural and ʟ- or ᴅ-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare (S)- and (R)-enantioenriched unsaturated amides by N-Alloc deprotection which induced concomitant

• conditions compatible with the double bond and acetal functions. In this work, we present Torii-type electrosynthesis of ester 3d (PG = Alloc) and its transformation to the enantioenriched vinyloxazoline building block 6, which can be used for the asymmetric synthesis of complex molecules [19][20][21][22][23

• ][24] (Scheme 1). The proposed strategy relied on the N-deprotection of the intermediate ester 3d inducing O-to-N rearrangement to form amide 5 as a precursor of vinyloxazoline 6. For this purpose, Alloc (allyloxycarbonyl) turned out to be a suitable N-protecting group as it was compatible with the

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