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

• diphosphate (DMAPP) from the mevalonate (MVA) and 2-C-methyl-ᴅ-erythritol 4-phosphate (MEP) pathways [2][3]. Sesquiterpenoids, synthesized from farnesyl diphosphate (FPP) which is composed of three C5 units, hold significant biological and industrial value, particularly in the realm of perfumery [4]. Among

• these, drimane-type sesquiterpenoids (DMTs) are distinct due to their chemical structures, which feature a decahydronaphthalene core adorned with methyl groups, mirroring the A/B rings found in labdane-derived diterpenoids [5][6] (Figure 1a). DMTs exhibit significant biological activities, such as those

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• our attention. Several meroterpenoids, alkaloids, polyketides, and sesquiterpenoids from the species displayed various biological properties including anti-inflammatory, antimicrobial, and cytotoxic activities [7][8][9]. In the present work, two rare new examples of sulfur-containing ovalicin

• sesquiterpenoids (1, 2), together with three known related analogs (3–5) [10][11][12][13] have been isolated and identified from the bioactive fraction of P. boydii CS-793. Details of the isolation and purification, structure elucidation, and biological evaluation of compounds 1–5 are described herein. Results and

• CS-793. To date, only three sulfur-containing ovalicin sesquiterpenoids have been reported [10][12]. Moreover, the first characterized crystal structure of an ovalicin-type sesquiterpenoid was obtained, which further confirmed the structures and absolute configurations of compounds 1–3. Biological

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect

• Ken-ichi Nakashima,
• Naohito Abe,
• Masayoshi Oyama,
• Hiroko Murata and
• Makoto Inoue

Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117

• potent compound 7 was found to significantly inhibit the production of IL-1β and IL-6 proteins, as revealed by the analysis of culture supernatants. Keywords: anti-inflammatory; Breynia disticha; RAW 264.7 cells; sesquiterpenoids; sulfur-containing compounds; Introduction Breynia disticha J.R.Forst

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• , Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, 518055, China 10.3762/bjoc.19.75 Abstract Five new eudesmane-type sesquiterpenoids (aquisinenoids F–J (1–5)) and five known compounds (6–10) were isolated from the agarwood of Aquilaria sinensis. Their structures, including

• revealed the structure–activity relationships (SAR). Keywords: agarwood; Aquilaria sinensis; SAR studies; sesquiterpenoids; Introduction Agarwood is the resinous wood of the Aquilaria species of the Thymelaeaceae family [1]. It is a precious traditional Chinese medicinal material and a kind of natural

• deep insight into novel molecules with effective bioactivities from agarwood. Therefore, the continued study of Aquilaria sinensis has led to the isolation of ten sesquiterpenoids, including five new eudesmane-type sesquiterpenoids (Figure 1). Herein, we describe the isolation, structural elucidation

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• and Technology, Qingdao, China State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China 10.3762/bjoc.18.91 Abstract One new aromadendrane-type sesquiterpenoid, namely ximaocavernosin P [(+)-1], and three new cadinane-type sesquiterpenoids

• -dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations or X-ray diffraction analysis. A plausible biosynthetic pathway of these sesquiterpenoids and their internal correlation were proposed and discussed. In an in vitro bioassay, (+)-aristolone (3) exhibited promising

• antibiotic effects [3][5][6]. Acanthella sponges have thus attracted much attention from marine natural products chemists and pharmacologists. The title animal is the most chemically studied species among the Acanthella sponges. Till now, more than 100 secondary metabolites belonging to sesquiterpenoids and

Analogs of the carotane antibiotic fulvoferruginin from submerged cultures of a Thai Marasmius sp.

• Birthe Sandargo,
• Leon Kaysan,
• Rémy B. Teponno,
• Christian Richter,
• Benjarong Thongbai,
• Frank Surup and
• Marc Stadler

Beilstein J. Org. Chem. 2021, 17, 1385–1391, doi:10.3762/bjoc.17.97

• antibiotic fulvoferruginin (1), fulvoferruginins B–F (2–6). The structures of these sesquiterpenoids were elucidated using HRESIMS, 1D and 2D NMR, as well as CD spectroscopy. Assessing the bioactivity, fulvoferruginin emerged as a potent cytotoxic agent of potential pharmaceutical interest. Keywords

• characterization. Results Structure elucidation of the secondary metabolites 2–6 Preparative HPLC of the supernatant crude extract of a submerged cultivation of Marasmius sp. strain MFLUCC 14-0681 in ZM½ media led to the isolation of six carotane sesquiterpenoids, fulvoferruginins A–F (1–6, Figure 1). The first

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• for the preparation of the enantiomers of other sesquiterpenoids by the addition reactions of tolylboronic acids to 3-methyl-2-cyclopentenone (Scheme 17) [13]. Also in 2020, Ochi et al. expanded the synthetic usability of 3-alkyl-3-arylcyclopentanones by developing a method for their Rh-catalysed

Muyocopronones A and B: azaphilones from the endophytic fungus Muyocopron laterale

• Ken-ichi Nakashima,
• Junko Tomida,
• Tomoe Tsuboi,
• Yoshiaki Kawamura and
• Makoto Inoue

Beilstein J. Org. Chem. 2020, 16, 2100–2107, doi:10.3762/bjoc.16.177

• [20][26], while three azaphilone-related polyketides, namely dothideomycetones A, B, and dothideomycetide A, were isolated from the CR17 fungal strain of the Dothideomycetes class (GeneBank accession number JQ867364) [27]. Furthermore, two sesquiterpenoids produced by Pithomyces chartarum

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• , and sesquiterpenoids, or scalarane-type sesquiterpenoids and sesterterpenoids from their sponge prey [23][37][38][39][40][41][42][43][44][45]. However, confusion in the chemotaxonomy of Chromodorididae arose by multiple changes in the species names, including splitting and synonymizations, and the

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• investigated Physarum polycephalum, a plasmodial slime mold also known as acellular amoeba. Plasmodia of P. polycephalum grown on agar plates were found to release a mixture of volatile terpenoids consisting of four major sesquiterpenes (α-muurolene, (E)-β-caryophyllene, two unidentified sesquiterpenoids) and

• PpolyTPS4 were able to produce sesquiterpenes and monoterpenes from the respective substrates farnesyl diphosphate and geranyl diphosphate. By comparing the volatile profile of P. polycephalum plasmodia and the in vitro products of PpolyTPS1 and PpolyTPS4, it was concluded that most sesquiterpenoids emitted

•  1B). The two unidentified are putative sesquiterpenoids. Compound 3 is a putative hydrocarbon sesquiterpene with a molecular mass of 204 (Figure 1C). In contrast, compound 4 has a molecular formula of C15H22O and a molecular mass of 218 (Figure 1C). It was predicated to be a sesquiterpene aldehyde

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• identification of the nanangenines – a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against

• : Aspergillus; biosynthesis; drimane; secondary metabolites; sesquiterpenoid; terpenes; Introduction The fungal genus Aspergillus is well recognised as a source of structurally diverse terpenoids comprising monoterpenoids [1], sesquiterpenoids [2][3][4][5], diterpenoids [6], sesterterpenoids [7][8][9

• [21], A. ochraceus [22], A. pseudodeflectus [17], A. carneus [23] and Aspergillus sp. strain IBWF002-96 [4][5] are biosynthetic sources of the drimane sesquiterpenoids. Drimane sesquiterpenoids, which are derived from a parent C15 pentamethyl-trans-decalin skeleton, are known to occur in plants

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• its extraordinary growth behaviour, the H. cf. alpina (strain 824) isolated during this study was selected for further chemical investigations. This led to the isolation of two novel compounds (1, 2). Compounds 1 and 2 belong to the bergamotene type of sesquiterpenoids, for which manifold ecological

Harnessing enzyme plasticity for the synthesis of oxygenated sesquiterpenoids

• Melodi Demiray,
• David J. Miller and
• Rudolf K. Allemann

Beilstein J. Org. Chem. 2019, 15, 2184–2190, doi:10.3762/bjoc.15.215

• synthesised in amorphadiene synthase-catalysed reactions from 8- and 12-methoxyfarnesyl diphosphates due to the highly plastic yet tightly controlled carbocationic chemistry of this sesquiterpene cyclase. Keywords: artemisinin; amorphadiene synthase; oxygenated terpenoids; sesquiterpenoids; substrate

• and functional groups to generate unnatural sesquiterpenoids that are not easily accessible by conventional organic synthesis [10][11][12][13][14][15][16][17][18][19]. Creating novel sesquiterpenoids, not normally found in nature, is of great interest due to the important applications of terpenoids in

• properties and are used to treat epilepsy [27][28]. This array of important compounds shows the potential of generating novel sesquiterpenoids with desirable bio-properties. ADS is a high fidelity sesquiterpene synthase that produces almost exclusively a single product. Its active site plasticity

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• ]. The C15 sesquiterpenoids constitute a large class of terpenoids with a wide range of industrial and commercial applications, including uses in flavours and perfumes, as bioactive molecules in the pharmaceutical industry, and in health care products [11]. Sesquiterpenoids are biosynthesised from the

• structurally diverse (poly)cyclic core skeletons [3][12]. A set of post-modification enzymes can transform core sesquiterpene skeletons into different kinds of sesquiterpenoids with potential anticancer, cytotoxic and antibiotic functions [13]. More than 121 skeleton structures derived from the sesquiterpene

• 5/6 bicyclic sesquiterpene with the molecular formula C15H26O (Figure 1). Interestingly, compound 1 contained a quaternary carbon with two methyl groups, which is uncommon for the cyclization mechanism of sesquiterpenoids and needs further investigation. Compound 2 was purified as a white powder. 1H

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• germination. The putative biosynthetic relationships between the isolated sesquiterpenoids were also explored. Keywords: Bipolaris sorokiniana; phytotoxicity; sesquiterpenes; terpenes; Introduction Fungi belonging to the genus Bipolaris (teleomorph: Cochliobolus) have been reported to produce a diverse

• chromatographed repeatedly with silica gel and RP-HPLC to afford four new sativene-type sesquiterpenoids, bipolenins K–N (1–4), along with eight previously reported compounds (5–12), which were identified as sativene-type sesquiterpenoids prehelminthosporol lactone (5) [1], helminthosporic acid (6) [1

• , 1.88, 2.65 and 3.77), which are typical resonances for sativene-type sesquiterpenoids. The NMR data for 1 were very similar to those for prehelminthosporol lactone (5) except for the replacement of a methine group (δC 32.1; δH 1.42) at C-9 in 5 with a hydroxylated quaternary carbon (δC 73.1) in 1. This

New terpenoids from the fermentation broth of the edible mushroom Cyclocybe aegerita

• Frank Surup,
• Florian Hennicke,
• Nadine Sella,
• Maria Stroot,
• Steffen Bernecker,
• Sebastian Pfütze,
• Marc Stadler and
• Martin Rühl

Beilstein J. Org. Chem. 2019, 15, 1000–1007, doi:10.3762/bjoc.15.98

• isolated. Our finding of the production of 1–4 by C. aegerita expands the number of secondary metabolites known from this fungus. From fungal cultures of the genus Cyclocybe the production of a broad variety of metabolites is known. This includes polyacetylenes [9][10] as well as sesquiterpenoids with

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• new halogenated laurane-type sesquiterpenoids, namely, isobromolaurenisol (1), clalaurenol A (2), ent-laurenisol (3), clalaurenol B (4), and the new aromadendrane-type sesquiterpenoid claaromadendrene (6), together with three known sesquiterpenoids (5, 7, and 8). Their structures were determined by

• sesquiterpenoids and diterpenoids with various intriguing carbon skeletons, such as nardosinanes, neolemnanes, and ylanganes [10]. Many of these secondary metabolites have attracted a lot of attention for further synthetic and pharmacological studies due to their potent bioactivities ranging from neuroprotective

• investigation of two title animals led to the isolation of four new halogenated laurane-type sesquiterpenoids 1–4, one new aromadendrane-type sesquiterpenoid 6) together with three related known compounds 5, 7 and 8 (Figure 1). Herein, the isolation, structure elucidation and bioactivity evaluation of these

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• starting from catechol derivative 142. Marine sesquiterpenoids are mainly known for their biological importance such as antitumor, antiviral and antibiotic properties [132]. In this report, the catechol-derived starting substrate 142 was cyclized to spirocyclic product 143 in 67% yield using PIFA (31) as

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ] sesquiterpenoids isolated from the sunflower Helianthus annuus [28][29][30][31][32][33], and it contains an unusual benzoxocane moiety. Owing to their unusual structures and biological activity, the heliannuols have attracted significant attention from synthetic chemists. The various approaches to the heliannuols

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• keto-oximes 179 and 2-amino derivatives 180 are β2-adrenergic agonists tested for bronchodilating activity. The pterosin family are sesquiterpenoids naturally occurring in bracken fern (Pteridium aquilinum), some of them exhibit antibacterial and cytotoxic activity. A practical synthesis of pterosin A

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• . Venustatriol (96) could then be obtained by C–C-coupling with the corresponding THP fragment in an enantioselective fashion. Glaciapyrrol A Glaciapyrrol A (100), B and C form a family of pyrrolo sesquiterpenoids which have been isolated in 2005 from a marine Streptomyces sp. (NPS008187) by Macherla et al. [161

New furoisocoumarins and isocoumarins from the mangrove endophytic fungus Aspergillus sp. 085242

• Ze’en Xiao,
• Senhua Chen,
• Runlin Cai,
• Shao’e Lin,
• Kui Hong and
• Zhigang She

Beilstein J. Org. Chem. 2016, 12, 2077–2085, doi:10.3762/bjoc.12.196

• derived from the South China Sea [10][11][12][13][14][15]. In a previous study, a chemical investigation of the endophytic fungal strain Aspergillus sp. 085242 allowed us to identify two novel sesquiterpenoids, asperterpenols A and B with an unusual 5/8/6/6 tetracyclic ring skeleton [15]. The unique

• structures of these sesquiterpenoids encouraged us to further study this fungal strain and continuous chemical investigation of it led to the isolation of two new furo[3,2-h]isocoumarins, asperisocoumarins A and B (1 and 2) and two new isocoumarins, asperisocoumarins E and F (5 and 6), together with five

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• chromatography): ethyl acetate–ethanol–water (9:2:10, v/v/v). The separation was carried out isocratically at a flow rate of 25 mL/min at 1200 rpm, affording seven fractions A to G. TLC of fractions B, C and F displayed a single spot corresponding to three new glycosylated sesquiterpenoids. Their structures were

• the polyphenols identified in Jungia species, sesquiterpenoids with guaiane, guaiene, nortrixane, trixane (isocedrene), and cyperane scaffolds are also representative of this genus [6][7][8][9]. These terpenoids demonstrated a wide range of bioactivities [10][11][12], and hit compounds such as

• configuration previously reported for trixanolides [34], led to identify compound 1 as a new member of the trixane sesquiterpenoids. The trivial name jungioside A was assigned. Compound 2 was obtained as a colourless gum. The molecular formula C21H30O8 was determined from its ESI–HRMS which gave the cationic

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• with the earlier report that stated 5 exhibits in vitro cytotoxicity against a number of cell lines (ED50 = 5 μg/mL). Members of the panicein family of aromatic sesquiterpenoids. Proposed biogenesis of panicein A2 (5). Retrosynthetic analysis of panicein A2 (5). Synthesis of ketone 13. Synthesis of

Thermal and oxidative stability of the Ocimum basilicum L. essential oil/β-cyclodextrin supramolecular system

• Daniel I. Hădărugă,
• Nicoleta G. Hădărugă,
• Corina I. Costescu,
• Ioan David and
• Alexandra T. Gruia

Beilstein J. Org. Chem. 2014, 10, 2809–2820, doi:10.3762/bjoc.10.298

• molecules (more bulky cyclic mono- and sesquiterpenoids) play an important role for encapsulation competitivity. However, the most concentrated sesquiterpene alcohol in the raw essential oil (α-cadinol (18), 6.2%) was more weakly encapsulated in β-CD (approximately 1%), likely due to its rigid structure and

• lower hydrophobicity in comparison with other sesquiterpenoids. The same observation was made for spathulenol (16), which had relative concentrations of 2.2% and 1.4%, respectively. Most of the other compounds were encapsulated at similar relative concentrations. Generally, oxygenated monoterpenes were

• degradation temperature (an of 83%, in comparison with 250% for non-encapsulated essential oil samples, Table 2 and Table 3). Similar behavior was observed for the case of sesquiterpenoids. An increase of 2.8–11.6% was observed for most of the sesquiterpene hydrocarbons and alcohols. For example, β-elemene (8