Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• ; C–H hydroxylation; chemoenzymatic synthesis; Mukaiyama hydration; protecting-group-free synthesis; Introduction Cardiac glycosides (CGs) are widely distributed natural products, generated by plants and amphibians [1]. Structurally, they are composed of an aglycone-steroidal moiety, an unsaturated

• absorption and metabolism, and specific moieties like rhamnose can enhance CG potency markedly by more than 25 times [1][7]. In addition, the -OH groups on the steroids’ structure also play an important role on their activity. However, these compounds are mainly isolated from plants or animals, which not

• isolated from the leaves and roots of the Japanese evergreen plant Rohdea japonica in 1951, and was also discovered in several other plants later [18]. Rhodexin A is the only natural CG that exhibits both cardiotonic activity and strong inhibitory activity on human leukemia K562 cells with an IC50 = 19 nM

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• objects for investigating the possibility of using them in the synthesis of compounds of iridoid topology. Iridoids belong to the class of terpenoids and are secondary metabolites of plants, as well as multi-tasking objects [5][17][18]. Studies on the pharmacological properties of iridoids have shown

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• alkaloids – a structurally diverse class of natural products found in plants of the widely distributed genus Lycopodium. Guided by biosynthetic hypotheses, Sarpong's group envisioned a divergent total synthesis of five lycodine-type Lycopodium alkaloids (including lycoplatyrine A (89)) used N-Boc-β

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

• (−)-aspidospermidine (−)-Hunterine A (14) and (−)-aspidospermidine (15) are monoterpene indole alkaloids, which were isolated from Hunteria zeylanica and Apocynaceae plants, respectively [56][57]. Structurally, these two natural products both contain the fused polycyclic skeleton core bearing four consecutive

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

• voatinggine and tabertinggine from the plants of Tabernaemontana (Apocynaceae) genus in Malayan, which are literally widely distributed in tropical America, Africa, and Asia [29]. Given the fact that these plants are rich sources of bioactive alkaloids, voatinggine and tabertinggine with unprecedented

• natural product ervaoffine D. Thus, through the bioinspired skeletal diversifications of (12-OMe)-tabertinggine, four iboga alkaloids could be powerfully synthesized. Bioinispired total synthesis of gymnothelignans The Gymnotheca (Saururaceae) genus only contains two species of plants, Gymnotheca

• chinensis Decne and Gymnotheca involucrate Pei. These two plants are endemic in China, and have been used as medicinal herb for a long history to treat diseases such as dysentery, abdominal distention, edema, contusion, and strains [31]. Since 2012, Zhou and co-workers extensively investigated the

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

• derived from evergreen trees found in tropical and subtropical regions of Africa, Australia, Central America, Polynesia, and Southeast Asia. Plants of the genus Alstonia have been used in traditional medicines to treat a wide variety of conditions, including coughs, dysentery, fever, malaria, rheumatism

• , sore throats, toothache, ulcers, and snake bites [1]. The medicinal qualities of these plants are ascribed to the presence of alkaloids, and they are rich in many different indole and oxindole alkaloids [2]. About 100 Alstonia alkaloids are known, with more being isolated on a regular basis [3][4

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

• sucrose derivatives in plants [79][80][81]. In this case, the carboxymethyl group in the 2-thioethyl fructofuranoside was locked by an intramolecular bridge formed by the TIPDS group to the C4–OH [1,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) bridge], resulting in a β-directing fructofuranosyl donor

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• biosynthesis; P450 oxidation; synthesis; Introduction Fusicoccanes are a family of 5-8-5 tricyclic diterpenoid natural products that are produced by bacteria, fungi, algae, and plants (Figure 1a) [1][2][3][4][5][6][7]. Fusicoccanes possess a broad range of biological activities, including anticancer, anti

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

• brevicarine (2) from (S)-brevicolline ((S)-1) (see Scheme 2) and their biogenetic relationship suggest that (S)-brevicolline could serve as a biosynthetic intermediate of brevicarine (2) in plants [19]. Brevicarine (2), isolated in 1967 from Carex brevicollis DC [27], has also been identified in various other

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• new, energy-intensive technologies and overconsumption of energy [1][2]. In this context, windpower plants and solar photovoltaic systems have become increasingly important contributions to the overall available energy, although both technologies still pose some problems regarding the storage of the

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

• of almost any bioactivity of interest that originate from plants, fungi, and even animals (such as sponges and corals). Perspective BGF can access only a fraction of the natural product chemical space For nearly a century, BGF has been the method of choice and identified the vast majority of natural

• . Structure prediction of natural products other than NRPs and PKs has historically progressed slower. However, it was not due to a lack of data. Indeed, terpenoids and alkaloids are the two largest families of natural products in plants and also represent a sizable minority in microorganisms. The lagging

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• conjugated base of the smallest dicarboxylic acid, stands out from the list of highly relevant analytes because oxalic acid is found in common edible plants and its corresponding dianion is tied to several diseases, e.g., the formation of kidney stones through complexation of calcium and precipitation of

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

• anticancer activity of these compounds. Keywords: cancerostatic activity; carbohydrates; heterocycles; N-glycosides; indirubin; Introduction Indigo (1a), known for more than 6000 years and originally produced from indigo plants in India, represents a famous traditional blue pigment which was an expensive

• controlled by such protein kinases. Therefore, the investigation of the influence of drugs on protein kinases plays an important role in current medicinal chemistry. Indigo naturalis is a traditional drug, derived from indigo plants, which has been used in China for centuries and also more recently against

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• interesting biological activities. Keywords: biosynthesis; fungal metabolites; polyketides; resorcylic lactones; total synthesis; Introduction Alternariol and some of its derivatives are ubiquitous as fungal metabolites present in infested plants and in food and feed, but similarly in soil, in wallpapers

• has been investigated thoroughly on its biological activities, especially on its toxicity [6][12]. Its phytotoxicity has already been noted in the first reports; it induced chlorosis when injected to the leaves of tobacco plants [110]. It turned out to be cytotoxic against HeLa and lymphoma L5178Y

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• constituting glycoproteins or glycolipids, respectively. Recently, glycan structures exposed on the cellular membrane have also been found to be associated with tRNA [2]. In other species, such as prokaryotes, plants or fungi, glycoconjugates comprise the cell wall, playing critical metabolic, structural and

• for humans, animals and plants, including drug design [14][15], vaccine development [15][16] and numerous other possibilities in the field of carbohydrate chemistry and biology. Notably, the regulation of the host immune response is often mediated by glycans, particularly through their recognition by

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• S55 in Supporting Information File 1). Biosynthetically, pyrrole-2-carboxylic acid is known to be derived from ʟ-proline [2]. Similarly, pyrrole-2-carbaldehydes have been isolated from various natural sources including plants, marine invertebrates, and fungi [7], while 1–5 are the first to have formyl

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• approach" merging efficient enzymatic synthesis – traditionally employed in the biosynthesis of natural products by microorganisms and plants – with precise chemical synthesis conducted by chemists. Chemo-enzymatic total syntheses reported recently fall into three main categories based on the purpose for

• ), trichodimerol (2), chalcomoracin (3), tylactone (4), and saframycin A (5), as well as a number of analogues of these natural products (Scheme 1). The overview of all five natural products begins with a description of the well-studied biosynthetic strategies evolved by microorganisms and plants. Biosynthetic

• highly substituted methyl cyclohexene core were isolated from plants of the Moraceae family as phytoalexins (Scheme 5) [44]. Since more than 160 related compounds have been discovered in an optically active form, Masamune, Takahashi, and colleagues postulated that the core scaffold is biosynthesized via

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• invertebrates and plants, perhaps hinting at these molecules being widely used alphabets in inter-organismal chemical cross talk. Non-ribosomally synthesized peptidic natural products Assembly line non-ribosomal peptide synthetases (NRPSs) are routinely detected to be encoded in Microbulbifer genomes [141]. An

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• discovering diverse natural products from bacteria and fungi. In plants, this approach is often more limited due to the lack of available annotated genomes and transcriptomes combined with a less consistent clustering of biosynthetic genes. The recently identified burpitide class of ribosomally synthesized

• and post-translationally modified peptide (RiPP) natural products offer a valuable opportunity for bioinformatics-guided discovery in plants due to their short biosynthetic pathways and gene encoded substrates. Using a high-throughput approach to assemble and analyze 700 publicly available raw

• transcriptomic data sets, we uncover the potential distribution of split burpitide precursor peptides in Streptophyta. Metabolomic analysis of target plants confirms our bioinformatic predictions of new cyclopeptide alkaloids from both known and new sources. Keywords: burpitides; natural products; plants; RiPPs

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• family members in bacteria and plants [4], these diterpenoids have four main structural differences: the number and location of oxidized carbons, the absence or presence of transannular ether bridges, the configuration (cis or trans) of the bicyclic ring fusion, and the presence and configuration (E or Z

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

• in a terpene hydrocarbon, or through nucleophilic water attack, yielding a terpene alcohol [5]. To date, about 80,000 terpenes and terpenoids have been discovered [3], approx. 10% of which are sesquiterpenes, composed of 15-carbon skeletons [6][7]. Sesquiterpenes are mainly distributed in plants and

• 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

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• diphosphate substrates MSTSs from plants Substrate-promiscuous TSs are widely spread in plants, which mainly produce linear terpenoids such as linalool (6), (E)-nerolidol (7) and (E,E)-α-farnesene (8) (Figure 2) [14][15]. Most plant MSTSs accept two prenyl substrates: C5 and C10 [16], C10 and C15 [17][18][19

• different subcellular compartments may facilitate the generation of multiple terpenoids in plants. Recently, in addition to linear terpenoid-producing TSs, MSTSs that form cyclic terpenoids have been discovered in plants, further increasing our understanding of chemodiversity and biosynthesis of plant

• terpenoids. LcTPS2 from Leucosceptrum canum was characterized as a versatile TS that generated six macrocyclic sesterterpenoids (11–16) and two macrocyclic diterpenoids (17,18), representing the first macrocyclic terpenoids isolated from plants (Table 1, Figure 2) [19]. In addition to linear prenyl

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• producers and of NNG is unknown. Additionally, NNG’s physiological function is unknown, but it is toxic to plants, mice, and Gram-negative bacteria [25][26]. While there is no direct evidence of the mechanism of this toxicity, NNG has been shown to competitively inhibit succinate dehydrogenase, a component

• , reductively decomposes the nitramine functionality of RDX to form •NO2 [38], a toxic reactive nitrogen species. Additionally, NNG is a structural analog of another natural product 3-nitropropionate (3NP) found in plants and fungi [39]. This highly toxic compound inhibited succinate dehydrogenase and other

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• University, Nanjing 211198, China 10.3762/bjoc.20.73 Abstract Drimane-type sesquiterpenoids (DMTs) are characterized by a distinctive 6/6 bicyclic skeleton comprising the A and B rings. While DMTs are commonly found in fungi and plants, their presence in bacteria has not been reported. Moreover, the

• performs a similar role to DrtB, engaging two P450s (AncE and AncB) to synthesize (+)-isoantrocin and (−)-antrocin [18]. Notably, the P450s identified in fungi and plants predominantly modify the B-ring of DMTs [15][16][18]. DMTs are commonly found in plants and fungi [6][9][13][15]. While enzymes

• derivatives 7–9. This study marks the first discovery of natural DMTs from bacteria and unveils the role of CavA in a novel late-stage modification pathway, expanding DMT biosynthesis beyond fungi and plants. Results and Discussion Discovery of three DMTs in S. clavuligerus S. clavuligerus is notably

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• environment in order to activate silent genes in actinomycetes. Actinomycetes mainly inhabit soils, but they are widely symbiotic with plants [103], insects [104], and other organisms [105][106], and there are reports of their secondary metabolites controlling their own physiological functions or functioning