Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• from mixtures of melifoliones 1 and 2 using the applied chemical methods. Thus, it is clearly proven, that 4 cannot be built as an artifact during the isolation. Therefore, it is likely that the biosynthesis of the quinol 4 occurs via enzymatically catalysed oxidation in the leaves of Melicope

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• . Glutaminases catalyze the hydrolysis of glutamine to glutamate, which supports the biosynthesis of amino acids, lipids, and glutathione and can also be oxidatively deaminated to α-ketoglutarate and enter the citric acid cycle. The “glutamine addiction” of cancer cells has made glutaminase an attractive

• ]. Glutamine serves as a nitrogen donor for the biosynthesis of asparagine, amino sugars, and nucleotides. Glutamine is also hydrolyzed to glutamate by glutaminase (GLS) enzymes, which are often overexpressed in cancer cells. The resulting glutamate supports the biosynthesis of glutathione and can be

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• -She Han and co-worker), bioinspired synthesis (review, Huilin Li, Xuegong She et al.), biosynthesis (fusicoccane diterpenoids, Yonghui Zhang, Ying Ye, Zheng Xiang et al.), chemoenzymatic synthesis (rhodexin A, Qianghui Zhou et al.)]; (ii) comparative analysis of target-oriented synthesis [complanadine

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• ring-expansion strategies in relevant natural product syntheses will be presented, demonstrating how synthetic chemistry can help to elucidate plausible biogenetic routes for structurally complex natural products. Keywords: biosynthesis; rearrangement; ring contraction; ring expansion; skeletal

• biosynthesis, when the oxidation state of the terpenoids is being adjusted [28][29][30][31][32][33][34][35][36]. Starting with an already substantial number of these common polycyclic frameworks and adding the almost unlimited variability for oxidative enzymatic C–H functionalisation, it is not surprising that

• terpenoids with completely unique carbon connectivity and ring systems are still discovered every single year. In this review article, intriguing examples of apparent ring contraction or expansion reactions of carbocycles in terpenoids, both in biosynthesis and application of similar tactics in the total

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• as a potent inhibitor of ornithine decarboxylase, the key enzyme that catalyzes the first step in polyamine biosynthesis [6]. This inhibition underlies both its therapeutic utility and its importance as a biochemical probe. From a structural standpoint, DFMO provides an intriguing case study for

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• containing a prenyl group at the 5, 6, or 7 positions are found as naturally occurring metabolites from diverse plant and bacterial sources [5][6][7]. The biosynthesis of prenyltryptophans is well studied and involves a series of prenyl transferases [12][13]. A series of 4-, 5-, 6-, and 7-prenylated 3

• Bock in 1987 [16]. It is of interest that although the biosynthesis of 3-indolylbenzoquinone-2,5-dione ent-5 is initiated with ʟ-tryptophan and anthranilic acid [17], the resulting natural products 1–4 possess a (3R) configuration. This is because of an epimerization mediated by the non-ribosomal

• peptide synthetase AnaPS within the genetic machinery of these microorganisms during biosynthesis [18][19]. Subsequently, post-translational enzymatic processes mediated by prenyl transferases (AnaPT) lead to prenylation at the C4–C7 sites in the indole unit. Terezine D (6), an indole-containing

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• alkaloids belong to the class of steroid alkaloids and are pseudoalkaloids, as they emerge biogenetically from steroidal biosynthesis via cholesterol and not, as usual for alkaloids, from amino acids [1]. For synthetic chemists, this combines challenges for steroid and alkaloid total synthesis and poses

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• ingenol [55]. Typically, the biosynthesis of polycyclic diterpenes occurs in two distinct phases: an initial cyclase-mediated cyclization phase to form the carbon framework, followed by an oxidase-catalyzed phase to install the requisite oxidation states. Inspired by this general biosynthetic pathway, the

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• isolated by Kobayashi and co-workers from the club moss Lycopodium complanatum [4][5][6][7]. They discovered that complanadine A exhibited neurotrophic activity by enhancing the mRNA expression level for nerve growth factor (NGF) biosynthesis in 1321N1 human astrocytoma cells and NGF production in human

• sequence of Boekelheide rearrangement (56 → 57), acetate hydrolysis, DMP oxidation and Cbz removal. Based on these results, Tsukano and co-workers suggested that a mono-N-oxide intermediate could be involved in the biosynthesis of these dimeric complanadine alkaloids. Importantly, access to both

• activity relationships, and generation of synthetic analogs, all of which pave the way for further study and development of this unique natural product and/or its analogs. Complanadine natural products and their plausible biosynthesis. The Siegel total synthesis of complanadine A enabled by [2 + 2 + 2

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

• enzymatic terpene cyclization and chemical synthesis [30][31][32][33]. Briefly, the carbon scaffolds are forged by terpene cyclases, followed by concise chemical transformations to yield the desired natural products. Here, we describe heterologous biosynthesis of cotylenol by engineering the biosynthetic

• pathway of brassicicenes in Aspergillus oryzae and harnessing the promiscuity of a cytochrome P450 from the biosynthesis of fusicoccin A (Figure 1b). A key intermediate, brassicicenes I (5), was further used to achieve the collective synthesis of alterbrassicicene E (6), brassicicenes A (7) and R (8

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

• remaining compounds showed activity at the highest concentrations tested. The plausible biosynthetic hypotheses toward the compounds were also proposed. Keywords: antiparasitic activity; biosynthesis pathway; phenolic siderophores; Pseudomonas species; pseudomonine; Introduction Species of the genus

• the biogenesis of this heterocyclisation leading to the pseudomonine biosynthesis [23]. The absolute configuration of the threonine residue in compounds 1 and 2 was assigned as ʟ, based on the derivatization of 1 and 2 hydrolysates with ʟ-FDAA, a Marfey’s reagent, followed by chromatographic profiling

• tentative biosynthesis follows that of pseudomonine, a non-ribosomally synthesized isoxazolidone produced by P. fluorescens. The previous studies on the biosynthesis revealed seven genes, three non-ribosomal peptide synthases (Pms D, E, G) and four precursor biosynthetic enzymes (Pms A, B, C, F) [23][24][25

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

• County, Sichuan Province, China, along with other borrelidin derivatives, including borrelidin E (Table 1, entry 8) and 12-desnitrile-12-carboxyborrelidin (Table 1, entry 19) [23]. The latter compound, found in both endophytic bacteria and as a product of borrelidin biosynthesis, contributed to the

• pioneering approaches: Morken (2003), Hanessian (2003), Ōmura (2004), and Theodorakis (2004). This review also included two synthetic studies by Haddad [30][31] and Negishi [49]. In 2011, Darna et al. expanded this scope by incorporating Omura’s 2007 method along with biosynthesis studies and investigations

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• elements of life processes including self- versus non-self-recognition, biosynthesis, molecular and ion transport, and replication. Beginning with the pioneering works of Pedersen, Lehn, and Cram, supramolecular chemists have studied the fundamental aspects of non-covalent interactions in organic solvents

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• antibiotic properties, others expand the chemical diversity and thus the functional sophistication of ribonucleic acids, as in the case of Q [3]. In most bacteria, Q biosynthesis is tightly regulated by riboswitches, which are highly structured RNA elements located mostly in the 5’-leader of messenger RNA

• . PreQ1 riboswitches sense the cellular concentration of preQ1 and regulate the expression of downstream located genes associated with the biosynthesis or transport of Q in a feedback-like manner. Binding of PreQ1 to the mRNA causes the riboswitch to commit an altered folding pathway, which affects the

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• spectrum to two sp3 carbon atoms at δC 67.8 (C-2') and 72.6 (C-3'), respectively. These results suggested that compound 1 possesses a tetramic acid moiety similar to prototenellin D (Figure 1), a precursor in the biosynthesis of tenellin [10], a 2-pyridone derivative purified from the entomopathogenic

• previously reported study investigating the biosynthesis of tenellin from Beauveria bassiana CBS110.25 [13], it was established that tenellin and a vast array of related metabolites could be synthesized through a cascade involving hybrid highly reducing polyketide synthase–non-ribosomal peptide synthetase

• (PKS–NRPS) [13]. Based on the structural relations between farinosones and tenellins differing only in the side chain length/the number of conjugated double bonds, farinosones were also postulated to be synthesized adopting a similar biosynthetic pathway. The biosynthesis of farinosones (Figure 4

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• -labeled ʟ-phenylalanine [19]. Therefore, the cyano group in bromotyrosine alkaloids containing the phenylacetonitrile moiety is derived from the α-carbon and amino group of ʟ-tyrosine. On the other hand, the biosynthesis of nitrile with a cyanoformamide moiety remains unclear. Ceratinadin G (1) represents

• a rare nitrile that contains a cyano group as aminoacetonitrile. The biosynthesis of the 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol scaffold has been proposed by Scheuer, Clardy and co-workers [5], but how the cyano group in 1 is biosynthesized remains unknown and is of

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

• product biosynthesis, along with all the information an organism needs, are encoded in its genome. Genetic information is transcribed and translated into proteins that carry out chemical reactions that sustain life, which include both primary metabolism and the biosynthesis of natural products. Direct

• need to wait for enzymes to complete the entire course of biosynthesis, and then characterize chemical structure of the final natural product. While a generalized algorithm is not yet available, scientists in recent years have made some headways toward predicting the chemical structure of a natural

• silico to avoid rediscovery. They are the cornerstone of chemical structure metagenomics; a few examples in this area of research are described below. NRP biosynthesis and structure prediction NRPs are biosynthesized by either type I or II nonribosomal peptide synthetase (NRPS) [50][51]. Type I NRPS is a

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

• ; metallocontainer; oxalate; Introduction Dicarboxylic acids and their corresponding anions are essential intermediates in the biosynthesis of proteins and important biological metabolites [1][2]. As a result, the development of receptors for this class of compounds is of high interest [3][4][5]. Oxalate, the

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• /ERG11 gene. This enzyme contains a haem-like prosthetic group in its active center and is a member of the cytochrome P450 family, which plays a key role in the biosynthesis of sterols. Sterols in turn are integral components of the fungal cell membrane, making inhibition of CYP51 [43] an effective

Young investigators in natural products chemistry, biosynthesis, and enzymology

• Jeffrey D. Rudolf,
• Lena Barra and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 2720–2721, doi:10.3762/bjoc.20.229

• . Their privileged structures have led organic and bioorganic chemists to develop methods to construct them. Our fundamental knowledge in enzymology is continually expanded by enzymes involved in natural products biosynthesis, as their production requires evolved enzymes to perform chemical reactions

• distinct from those seen in primary metabolism. Natural products have inspired generations of scientists and continue to do so today. This thematic issue highlights young investigators in natural products chemistry, biosynthesis, and enzymology. As early-career researchers ourselves, we are honored to

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• gap between m/z 192 and 232 indicates a methyl group either at either C-5 or C-6. Taken together, the data from the derivatizations led to the conclusion that one methyl group is located at C-4 and a second at C-6. This is consistent with regular fatty acid biosynthesis of mid-chain methyl

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• fungi, are discussed with view on their isolation, structure, biological activities, biosynthesis, and total syntheses. This class of compounds consists until now of 127 naturally occurring compounds, with very divers structural motifs. Although only a handful of these toxins (i.e., alternariol and its

• 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

• 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

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• spontaneously form in bovicin HJ50 to exert their natural activity and change spectra of antimicrobial effects when synthetically intramolecularly bound [17][18]. The biosynthesis of mature lanthipeptides involves the translation of lanA, which encodes a precursor peptide with two regions: a leader peptide that

• biosynthetic clusters or superclusters these precursor peptides belonged to contained all the genes lanA, lanM, and lanT. These genes were found to be the minimal machinery required for lanthipeptide biosynthesis (Figure 2). Notably, transporter genes and regulatory elements were not considered in the second

• filter as their presence is not needed for biosynthesis, albeit it is for resistance. As a result, the C. cellulovorans 743 clusters were chosen because they were thought to be complete, novel, and most interesting, primarily due to the presence of two different, apparently independent operons, each with

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

• isolated from Alternaria brassicicola, a phytopathogenic fungus that causes dark leaf spots in Brassica species. The biosynthesis process of brassicicenes was primarily elucidated through in vitro enzymatic transformations and heterologous expression using Aspergillus oryzae. The proposed biosynthetic

• pathway of brassicicenes in Pseudocercospora fijiensis is outlined based on an investigation by Oikawa and co-workers [23]. The biosynthesis begins with the conversion of farnesyl pyrophosphate (FPP) and isopentenyl pyrophosphate (IPP) to geranylgeranyl pyrophosphate (GGPP), catalyzed by the

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• within the context of ribosomally synthesised and post-translationally modified peptide (RiPP) natural products. Methyltransferases play a pivotal role in the biosynthesis of diverse natural products with unique chemical structures and bioactivities. They are highly chemo-, regio-, and stereoselective

• -translational modifications; ribosomal peptides; SAM-dependent enzymes; Introduction In the complex landscape of natural product biosynthesis, ribosomally synthesised and post-translationally modified peptides (RiPPs) stand out as a fascinating class of compounds with both structural diversity and unique

• encoded in the same BGC as the precursor peptide install post-translational modifications in the core peptide. Finally, a protease releases the modified core peptide, creating the mature natural product [2]. The transfer of a methyl group is a common post-translational modification in RiPP biosynthesis