Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• therapeutic methods [78][79][80]. Such reactions can be performed at particular locations such as DNA or tubulin, when the photocatalyst is placed via a tethered ligand (Scheme 17) [81]. In the present case, the triarylmethine dye 67 was used as sensitizer. It is in equilibrium with the lactone form 68 and

• can bind either to tubulin or DNA depending on the conjugate R. The lactone form enables cell-permeability. The bioactive compound 69 causes microtubule depolymerization and it is caged in the dihydrotetrazine derivative 70. Upon photocatalyzed oxidation, the corresponding tetrazine compound 71 is

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• cyanoacetic ester and acetylacetone. The configuration of the products 4 and 5 was established by bromination of a small amount of these isomeric compounds in CDCl3 (Scheme 6) and subsequent analysis of the mixture by 1H NMR spectroscopy. For the stereoisomers 4, the main product was lactone 22, identified by

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• -catalyzed (3 + 3) annulation [29]. A broad scope was demonstrated, comprising more than 50 diversely substituted compounds (Scheme 10). Wong, Zhao, and co-workers disclosed the intriguing formation of bridged biaryls featuring eight-membered lactone rings 32 [30]. This serendipitously discovered

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• enough to displace the iodane to form the oxonium species A. When the carboxylic acid is used, the oxygen in the lactone intermediate is less reactive and so substitution of the iodane by fluoride is more favourable and the branched product is formed. In addition to aminofluorination, Szabó also reported

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• may also benefit from bioinformatic studies of adenylating enzymes in general; the discovery of a novel β-lactone biosynthesis pathway in Nocardia species is a good case in point [78]. Future directions 2: Understanding thioesterase function No algorithm is currently capable of predicting the topology

• to fully understand the determinant(s) of NRP topology. There are many ways to classify NRPs when topology and chemical structural features are considered simultaneously. For example, a macrocycle may be a lactam or a lactone depending on whether the internal nucleophile is an amine or an alcohol

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• % yield (Scheme 38) [59]. Unfortunately, all attempts to achieve a deprotection failed, due to cleavage of the lactone moiety. Starting with α-configured isatin-N-rhamnoside α-16a, anomerically pure α-64a could be prepared in 43% yield. Likewise, N-rhamnoside β-64b, N-glucoside β-64c, N-mannoside β-64d

• , due to cleavage of the lactone moiety. Starting from the respective isatin-N-glycosides, N-glucoside β-74b and N-mannoside β-74c were prepared. Carboisoindigo-N-glycosides The condensation of isatin-N-rhamnoside β-16a with indan-2-one (76) afforded carboisoindigo-N-rhamnoside β-77 in 39% yield (Scheme

•  42) [60]. Despite the absence of a lactone moiety, deprotection proved to be unsuccessful, due to decomposition. Miscelleaneous 6H-Indolo-[2,3-b]quinoxaline-N-glycosides The cyclization of isatin-N-rhamnoside β-16a with 1,2-diaminobenzene (79a) afforded 6H-indolo-[2,3-b]quinoxaline-N-glycoside β-80a

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• during the lactone-forming process. Their close structural resemblance led to a significant peak overlap both in the 1H and 19F NMR spectra which made it difficult to obtain their exact ratio and thus, the combined 19F NMR yields were shown in Table 4. Separation of these two compounds was eventually

• succeeded by the usual hydrogenolysis to furnish the carboxylic acid anti,syn-8a in 79% isolated yield and the lactone anti,syn-7b was recovered in 13% yield (Scheme 4) which was considered to be the reflection of the original composition of anti,syn-7a and -7b. The relative stereochemistry of anti,syn-8a

• was confirmed as 2,3-anti-3,4-syn by its X-ray crystallographic analysis [49] (Figure 2) whose construction could be readily understood as the result of a highly stereoselective SN2-type epoxy ring opening of 2a, followed by the intramolecular lactone formation with the pro-R ethoxycarbonyl group

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• acid), whose biosynthesis is presumably starting from alternariol. The lactone moieties of these compounds are usually six-membered rings, where variations during or after polyketide synthesis occasionally give rise to five- or seven-membered rings or even to open structures with a free resorcylic acid

• pathogens [50][51][52]. It should be noted that Alternaria alternata is a species complex and many producer strains reported in the literature were not correctly identified [53]. The rather low toxicity of alternariol and most of the further Alternaria toxins (especially those with resorcylic lactone

• only due to its structural analogy to the other lysilactones; it is not a resorcylic lactone and has not been mentioned after the initial report [139]. The structures of these compounds were determined by NMR-spectroscopic methods and constitution and configuration of lysilactone A was further

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• enantioselectivity. The reactions of α,α-dialkyl-5-hexenoic acids 2e and 2f gave the corresponding bromolactonization products 3e and 3f with moderate enantioselectivities. The present catalytic method could also be applied to the asymmetric synthesis of spirolactones [37][38][39]. For example, α-spiro-δ-lactone

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• cyclopamine. Comparing the biological results of the compound with the activity of desmethylveramiline (a des-E analogue of cyclopamine) has suggested that the rigidity of the oxetane ring is crucial for the potency of compound 7 [12]. Spiro-β-lactone steroids Beller et al. reported a selective method for

• -Methylene spirolactones at C-3 11a and 11b derived from dihydrocholesterol and stanolone were also obtained in 41% and 52% yields, respectively (dr > 20:1) (Scheme 3). More recently, a functionalized spiro-β-lactone was obtained via a metal-free procedure involving photoinduced carbene C–H insertion in a

• C–H insertion to produce the spiro-β-lactone was accomplished by simply exposing the diazo derivative to 440 nm blue LEDs (Kessil lamp) at 50 °C, that favored the formation of a singlet carbene that reacted selectively by insertion into the C(3)–H bond. Spiro-lactones 14 were obtained in 80% yield

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• tetracyclic cage compound 51. Acetal opening in 51 afforded the keto-aldehyde 52 which underwent an intramolecular Cannizzaro reaction to give the trihydroxy acid 53, finally cyclizing to the lactone diol 54, elaboration of which led to the desired target (Scheme 18). An interesting application of the

• intramolecular Cannizzaro reaction was demonstrated by the group of Schmalz in the total synthesis of the marine antibiotic pestalone [86]. They observed a facile isomerization of the pestalone derivatives 55/57 into the intramolecular lactone derivatives rac-56a,b which features a Cannizzaro–Tishchenko-type

• -Cannizzaro reaction in the construction of the spiro-β-lactone ring while targeting the spiro-β-lactone-γ-lactam ring of oxazolomycin and lazollamycin [88]. Proceeding towards the requisite fragment they envisaged a series of crucial diastereoselective transformations arriving at the precursor 69 to the

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• scaffolds (Scheme 1) [1][2][8][9][10][11][12][13][14]. Noteworthy is the prerequisite for FADH2/FMNH2, provided by E. coli Fre or flavin reductases in corresponding biosynthetic pathways, to facilitate these oxidation reactions. Experimental data support that 1 was firstly oxidized to a lactone intermediate

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• anticancer, antimalarial, antibacterial, and antiviral activity [8][9]. For instance, the well-known artemisinin family of drugs, which is currently the first line of treatment against malaria, is a sesquiterpene lactone [10]. Sesquiterpenes produced by plants [10] also have plant growth regulating and

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• small amounts of the C2 epimers. Oxidation of the hemiacetal 12a gave a moderate and unoptimised yield of 40% for lactone 24. The probable mechanism for the transformation with SOCl2 and under Appel conditions is shown in Figure 2. The reaction of alcohol 10 with the electrophiles gives the

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• pristinamycin I NRPS. This TE domain showed activity for hydroxy groups and amines to form either lactone or lactam, and the broad substrate scope made this strategy potent for modifying the bioactivity of streptogramin antibiotics. In 2007, the same laboratory identified the interactive TE domain of the

• TE-catalyzed marcolactonization [69]. The synthesis of linear peptide 34 commenced with the lactone opening of 26 to afford Weinreb amide 27. Following primary alcohol protection and amide reduction, the aldehyde 28 was coupled with iodide 29 to afford 30 via Nozaki–Hiyama–Kishi coupling, which was

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• 21.0 and one at δC 25.2 attached to the alternariol basis skeleton (Figure 2, Table 1); four methines (δC 117.0, 101.1, 109.6, 108.6), and eleven quaternary carbons including the signal of the lactone carbon at δC 158.5 (C-6) and those of the three sp2 oxygenated carbons at δC 156.9, 154.2, and 153.2

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• carried out by condensation of acetophenones with chloral under reflux in acetic acid using the known literature procedure [19] (Scheme 2). Based on another literature approach [20], compounds 1p–v were obtained by acylation of electron-donating arenes with Wynberg lactone [21] (Scheme 3). Additionally

• condensation of acetophenones with chloral in refluxing acetic acid. Synthesis of 1-aryl-4,4,4-trichloro-3-hydroxybutan-1-ones 1p–v by acylation of electron-donating arenes with Wynberg lactone. Synthesis of 1-aryl-4,4,4-trichlorobut-2-en-1-ones 2 by dehydration of hydroxy ketones 1. Cyclization of 1-aryl

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• an example of β-dicarbonyl functionalization. Metal-free cyclopropanations of iodonium ylides, either as intermolecular (a) or intramolecular processes (b, c). Metal-free intramolecular cyclopropanation of iodonium ylides. Reaction of ylide 6 with diphenylketene to form lactone 24 and 25. Indoline

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• products, demonstrating a clear preference for addition to alkenes even in the presence of alkyne functionalities. Due to basic conditions of the reductive quenching (RQ) route, the formation of lactone side product 30h could be observed with a carboxylic acid functionality. In the absence of Et3N, the

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• (71b) and 2-ethoxy-3-methyl-5-methylene-5,6,7-trihydro-1,2-oxaphosphepine 2-oxide (72b) in 85:15 in a total yield of 64% (Scheme 15) [36][37]. To prepare a hapten for the production of the catalytic antibody for the catalytic formation of a 14-membered lactone, because it is very difficult for the

• followed by hydrogenolysis in the presence of Pd/C as a hapten to produce an antibody. The antibody can catalyze the formation of a difficultly synthesized 14-membered lactone [24]. 2 Synthesis via annulations Annulations are alternative strategies for the synthesis of medium and large phostam, phostone

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• -unsaturated γ-lactone ring. The HMBC cross-peaks (Figure 2) from H-11 (δH 5.86) to C-10, C-12, and C-13, and from H-15 (δH 6.03) to C-12, C-13 and C-14 allowed the location of an extended conjugated π-system at C-11 and C-12. Moreover, the downfield shift of C-14 (δC 72.2) and the HMBC correlation between H3

• -lactone functionality. The 13C NMR and DEPT spectra in combination with HMQC data (Table 1) showed resonances of 44 carbons which were classified as nine methyls, 11 methylenes, 11 methines (three oxygenated sp3 at δC 73.7, 69.4, 68.8), and 13 quaternary carbons (four carbonyls at δC 197.9, 170.7, 170.4

• ′-acetoxypterolobirin B (3) together with one known analogue were isolated from the MeOH extract of P. macropterum fruits. Their structures and absolute configurations of 1 and 3 were established by spectroscopic analyses and ECD data. Compound 1 has an extended conjugated π-system with an α,β-unsaturated γ-lactone

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• successfully treated by artemisinin combination therapy (ACT). Artemisinin can be isolated from the Artemisia annua (sweet wormwood) plant. This sesquiterpene lactone bearing a peroxide is a prodrug of the biologically active dihydroartemisinin. In 2012, Zhu and Cook developed a gram-scale asymmetric total

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• equivalents of water interrupted the cyclization step and led entirely to reductively coupled alkenylated ring-opened products. Interestingly, when this methodology was applied to the ester-bearing oxabicyclic 1a, the anticipated reductive coupling product was not detected; instead, bicyclic γ-lactone 4 was

• solely observed (Scheme 1). This unprecedented lactone is presumed to be generated through the expected reductive coupling to generate the ring-opened intermediate 5 which undergoes subsequent intramolecular lactonization with the distal ester group. In the same year, Cheng and co-workers observed the

• undergo the domino reaction, generating the desired bicyclo[2.2.2]lactone 136. The authors proposed the reaction first takes place through an ARO of the doubly bridgehead-substituted oxabicyclic alkene with the secondary amine nucleophile ultimately producing 137. The Rh(I) catalyst then facilitates the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• potassium carbonate or methylcopper in pyridine led to compound 116 in only 10% yield. The cleavage of the benzyl ether proved to be complicated, as TFA also opened the lactone at the ester group (Scheme 24) [55]. In an attempt to circumvent these problems, the authors chose to use isovanillin (80) as