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

• analogs. This discovery not only broadens the known chemical diversity of DMTs from bacteria, but also provides new insights into DMT biosynthesis in bacteria. Keywords: bacterial terpenoid; cytochrome P450s; drimane-type sesquiterpenoid; Streptomyces clavuligerus; terpenoid biosynthesis; Introduction

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

• and mass spectrometric data. X-ray crystallographic analysis confirmed and established the structures and absolute configurations of compounds 1–3, thus providing the first characterized crystal structure of an ovalicin-type sesquiterpenoid. In the antimicrobial assays, compounds 1–3 showed broad

• -spectrum inhibitory activities against several plant pathogens with MIC values ranging from 2 to 16 μg/mL. Keywords: antimicrobial activity; cold seep; Pseudallescheria boydii; sesquiterpenoid; Introduction Marine cold seeps are typical of chemosynthetically driven ecosystems, characterized by methane

• stereogenic centers in compound 1 as 1R, 2R, 3R, 6R, 7R, 8S. This is likely the first characterized crystal structure of an ovalicin-type sesquiterpenoid. The molecular formula of pseudallene B (2) was assigned as C15H26O5S (three unsaturations), with one CH2 unit less than 1, based on positive HRESIMS data

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

• glycosides [1][2][3], flavan-3-ol glycosides [4], alkaloids [5], and phenolic glycosides [5][6]. Notably, sulfur-containing spiroketal glycosides, represented by breynins and epibreynins, have characteristic sesquiterpenoid-derived structures. The sesquiterpenoid phyllaemblic acid and its glycosides, which

• the onset of anti-inflammatory action. Conclusion The biosynthesis of breynins with novel skeletons remains poorly understood, especially with respect to the sulfur source. In this study, we isolated a new aglycone, probreynogenin (3), together with a known sesquiterpenoid, phyllaemblic acid (5

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• the (3 + 2) cycloaddition pathway under simple acid-promoted conditions, without notable problems of styrene oligomerization or homodimerization. The method allowed a short racemic total synthesis of the sesquiterpenoid cuparene (±-98, Scheme 14d), wherein the synthetic challenge of the contiguous

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• aminobisabolene sesquiterpenoid halichonic acid ((+)-1) from the sponge Halichondra sp. (Figure 1) [4]. This amino acid natural product features a rigid 3-azabicyclo[3.3.1]nonane ring system containing four stereogenic centers within the piperidine ring. In 2021, the same group re-isolated (+)-1 from the sponge

• report the first syntheses of the enantiomers of these natural products (i.e., (−)-1 and (−)-2), confirming the structural assignments of the halichonic acids and establishing their absolute configurations. Results Our synthetic route began with the readily available sesquiterpenoid (−)-α-bisabolol (3

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

• anti-inflammatory activity by the inhibition of LPS-induced TNF-α and CCL2 release in RAW 264.7 macrophages. Keywords: Acanthella cavernosa; anti-inflammatory; biosynthetic pathway; chiral separation; marine sponge; sesquiterpenoid; Introduction Marine sponges of the genus Acanthella (class

• sample on a large scale manner (310 g, dry weight). As a result, besides the already reported nitrogenous sesquiterpenoids, nine non-nitrogenous sesquiterpenoids, including a new aromadendrane-type sesquiterpenoid [(+)-1] and three new cadinane-type sesquiterpenoids [(+)-4, (+)-5, and (−)-5], together

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

• : antibiotics; Basidiomycota; carotane; fulvoferruginin; Marasmius; sesquiterpenoid; Introduction The family Marasmiaceae (Agaricomycetes, Basidiomycota) presently contains ten genera with Marasmius Fr. being the predominant one (currently comprising over 600 recognized species). Most of these fungi are

• moderate antifungal activity. A recent find of a Marasmius species in Northern Thailand led, however, to the isolation and identification of five novel derivatives of this carotane-type sesquiterpenoid. The present study is dedicated to describing their isolation, and biological and physicochemical

• structure resembling that of the carotane sesquiterpenoid fulvoferruginin (1, [8]) with the only difference being a tertiary methyl group at C-14 (δC/H 8.7/1.20), instead of an olefin. Compound 2 was therefore named fulvoferruginin B. Subsequently, a minor peak following 2 in the HPLC chromatogram was

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• of undifferentiated cells with malformed cell walls [8][10]. Up to now, the bacterial sesquiterpenoid thallusin, released by Maribacter spp. [11][12], is the only known AGMPF that induces morphogenesis such as rhizoid and cell-wall formation in Ulva spp. [11][12] or thallus development in Monostroma

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• catalyzed by Grubbs 2nd generation Ru-carbene, these intermediates then led to the tricyclic sesquiterpenoid-like scaffolds I–VIII (Scheme 4), as suitable precursors for the synthesis of artemisinin and its analogs (1a–c). After selecting the optimal tricyclic intermediate, the installation of the bridged

• synthesis of the marine sesquiterpenoid (−)‐clavukerin A (9) and its stereoisomer (−)‐isoclavukerin A (10, Scheme 13). The sterically related analogs (+)-clavularin A and clavularin B have also been produced by this protocol. It is noteworthy, that the authors succeeded in preparing the two enantiopure

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

• : 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

• File 1) yielded ten drimane metabolites shown in Figure 1: one trihydroxylated drimane sesquiterpenoid lactone, nanangenine A (1), four drimane lactones bearing C6/C8 acyl chains, nanangenines B, C, D and E (2, 4, 5 and 6), two acylated drimanes bearing isomeric lactones, isonanangenines B and D (3 and

• ), three methyl groups (C-13, C-14, C-15) and three hydroxy groups (1-OH, 6-OH, 9-OH). Detailed analysis of the 2D NMR data for 1 (Table S3 in Supporting Information File 1) confirmed the presence of a drimane sesquiterpenoid lactone scaffold. A search of the literature revealed 1 to be almost identical to

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

• analysis (Figure 1) of the organic soluble products formed from 8-methoxy FDP (11) through ADS catalysis revealed the formation of a major sesquiterpenoid of molecular mass 234 (85%). No organic soluble products were detected when ADS was omitted from the incubation mixture. This product was identified as

• 8-methoxy-γ-humulene (20) by NMR spectroscopy and comparison of its 1H NMR spectrum (Figure 2) with that of 8-oxo-γ-humulene, a natural sesquiterpenoid isolated from the plant Cineraria fruticulorum [36]. The signals for H5 (δH = 5.44 ppm, d, JH,H = 16.0 Hz), H6 (δH = 6.06, d, JH,H = 16.0 Hz), H15

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

• products, heterologous expression of various sources of terpene synthases in Escherichia coli and Saccharomyces cerevisiae is a feasible approach [25][26]. In this study, a combination of genome mining and metabolic engineering was used for sesquiterpenoid discovery, utilizing farnesyl diphosphate

• represent the esterification reaction during the extraction process. The 5/6 bicyclic sesquiterpene identified and characterised in this study was a brasilane-type sesquiterpenoid; this sesquiterpenoid type is typically isolated from cultures of the basidiomycete Coltricia sideroides in combination with its

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

• Sciences, Macquarie University, Sydney, NSW 2109, Australia 10.3762/bjoc.15.198 Abstract Chemical investigation of the barley and wheat fungal pathogen Bipolaris sorokiniana BRIP10943 yielded four new sativene-type sesquiterpenoid natural products, bipolenins K–N (1–4), together with seven related known

• strain BRIP10943 (CS10) [14] and their phytotoxicity. This led to the isolation of four new sativene-type sesquiterpenoid natural products along with seven related known analogues and one sesterterpenoid. Herein, the isolation, structure elucidation and phytotoxic activities of these compounds are

• responsible for production of 12. We are currently investigating the genetic basis for the biosynthesis of the sativene-type terpenoid compounds identified from B. sorokiniana. Conclusion Following the first and only reported isolation of a sativene-type sesquiterpenoid, sorokinianin (11), from B. sorokiniana

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

• illudine [11], aromadendrane [12], marasmene [13] and fomannosane [14] type skeletons. Although bovistol could formally be supposed to be a triterpene, it is thought to be derived by a hetero-Diels–Alder reaction of two sesquiterpenes to form a dimeric sesquiterpenoid [15]. In the recently published genome

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

• extensive spectroscopic analysis and by comparison with the previously reported analogues. In a bioassay, compounds 1, 2 and 4 exhibited interesting inhibitory activities in vitro against PTP1B and NF-κB. Keywords: Clavularia viridis; Lemnalia flava; NF-κB; PTP1B; sesquiterpenoid; soft coral, terpenes

• 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

Investigation of the electrophilic reactivity of the biologically active marine sesquiterpenoid onchidal and model compounds

• Melissa M. Cadelis and
• Brent R. Copp

Beilstein J. Org. Chem. 2018, 14, 2229–2235, doi:10.3762/bjoc.14.197

• trimers. Taken together, these results support the hypothesis that onchidal (6) could be used in chemical defense in a similar manner to related sesquiterpenoid dialdehydes and enol esters. Masked and unmasked 1,4-dialdehyde natural products 1–6. Target onchidal model compounds 11–18. Pyrrole product 29

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

• iodonium diacetate 132 in 2,2,2-trifluoroethanol/DCM at −10 °C (Scheme 51). Additionally, the synthesized functionalized spirodienone 140 was used as precursor for the synthesis of (+)-plicamine (141). In 2002, Quideau and co-workers [131] developed the synthesis of marine sesquiterpenoid (+)-puupehenone

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

• -pinene or limonene [78]. At present, 27.4 g/L of amorphadiene is the highest published titer for any reported terpenoid produced in E. coli. This result is of particular industrial relevance as amorphadiene constitutes the sesquiterpenoid scaffold of the antimalarial drug artemisinin [79]. In comparison

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

• classified taking into account the terpenoid structure (mono- and sesquiterpenoid hydrocarbons (M and S), oxygenated mono- and sesquiterpenes (OM and OS), as well as the cycle numbers (1/2/3/4 included in the sample code), which indicates the structure rigidity/flexibility). The PCA variables are the

• related to a score plot that associates similarities between structures. The axis rotation parameters provide a loading plot, which indicates the importance of the parameters for this analysis. The bi-dimensional PCA analysis clearly classifies the sesquiterpenoid hydrocarbons in the upper region of the

• variables. The O. basilicum L. essential oil components were encoded, according to the terpenoid classification, as monoterpenoid hydrocarbons (M), oxygenated monoterpenes (OM), sesquiterpenoid hydrocarbons (S), and oxygenated sesquiterpenes (OS). Furthermore, the number of cyclic moieties in the terpenoid

Formal total syntheses of classic natural product target molecules via palladium-catalyzed enantioselective alkylation

• Yiyang Liu,
• Marc Liniger,
• Ryan M. McFadden,
• Jenny L. Roizen,
• Jacquie Malette,
• Corey M. Reeves,
• Douglas C. Behenna,
• Masaki Seto,
• Jimin Kim,
• Justin T. Mohr,
• Scott C. Virgil and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2014, 10, 2501–2512, doi:10.3762/bjoc.10.261

• formal total syntheses of an array of classic natural products including sugar derivatives, terpenes, and alkaloids, adding significantly to the growing list of uses for this powerful C–C bond construction. An efficient route to the sesquiterpenoid (−)-thujopsene (10) has been delineated, allowing access

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• supports our proposed structure. The HRMS-ESI(−) spectrum for siphonodictyal E4 (4) showed the pseudomolecular ion peak [M + Na − 2H]− at m/z 555.0954, confirmed its molecular formula as C22H30O11S2, corresponding to eight double bond equivalents. The sesquiterpenoid moiety of the molecule contained two

• siphonodictyal E4 (4a). Proposed biogenesis of 4a starting from the hypothetical precursor 3-ox with an acyclic sesquiterpenoid part. Hypothetical biogenesis of the bicyclic sesquiterpenoid moiety from the acyclic precursor of the siphonodictyals in the sponge Aka coralliphagum [11]. The newly formed bonds from

• the acyclic to the bicyclic sesquiterpenoid moiety are drawn in red. The isomerizing double bond is drawn in blue. NMR data of compounds 1–5 (δC 150 MHz, δH 600 MHz in DMSO-d6).a 13C substituent effects Δδ in monosubstituted benzenes relative to the benzene carbon at 128.5 ppm [9]. Results of the

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• divinylcyclopropane–cycloheptadiene rearrangement starting in 1991. Earlier classic syntheses of sesquiterpenes are described to underline the synthetic power in the total synthesis of sesquiterpenoid natural products. The title reaction has been subject to previous reviews [5][6], partial overlap with the content of

• the cytotoxic sesquiterpenoid quadrone (55) from Aspergillus terreus [52][53] started from tricyclic ketone 52 [54], which was converted into tricycle 53 in 12 steps. Trans-divinylcyclopropane 53 underwent the desired DVCPR after trans-cis-isomerization of the vinyl moiety at 175 °C, forming bridged

• sesquiterpenoid sinularene (59) from the coral Sinularia mayi [58] started from alcohol 56, which was converted to bicyclic 57 in nine steps. Trans-divinylcyclopropane 57 was then subjected to high temperature DVCPR conditions furnishing bridged bicycle 58. Trans-cis isomerization of the vinyl moiety had to take

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• are unknown. The sesquiterpenoid stachyflin (156) was first isolated from the fungus Stachybotrys sp. RF-7260 by Shionogi & Co., Ltd., Japan, in 1997 [130] and shows outstanding antiviral activity against the influenza A subtype H1N1 (IC50 = 3 nM), outperforming current drugs such as amantadine and

Carbamate derivatives and sesquiterpenoids from the South China Sea gorgonian Melitodes squamata

• Li-Si Huang,
• Fei He,
• Hui Huang,
• Xiao-Yong Zhang and
• Shu-Hua Qi

Beilstein J. Org. Chem. 2012, 8, 170–176, doi:10.3762/bjoc.8.18

• rarely found in marine natural compounds, and 7 showed moderate antibacterial activity. The possible biosynthesis routes of 1–5 were conjectured. Keywords: carbamate; gorgonian; Melitodes squamata; sesquiterpenoid; Introduction Gorgonians are recognized to mainly produce acetogenins, sesquiterpenoids

• sesquiterpenoid with a methoxy group and a side chain that contained three methylene carbons. This suggestion was proved by the HMBC correlations (Figure 4). In the HMBC spectrum of 6, correlation of MeO– (δH 3.16, s) with δC 79.1 indicates the methoxygenation of C-10. The HMBC correlations of H-16 [δH 2.72 (d, J

Toward an integrated route to the vernonia allenes and related sesquiterpenoids

• Da Xu,
• Michael A. Drahl and
• Lawrence J. Williams

Beilstein J. Org. Chem. 2011, 7, 937–943, doi:10.3762/bjoc.7.104

• such structures are largely unexplored, we focused on the vernonia allenes. Moreover, we expected that such allenes contain the coded reactivity to access many sesquiterpenoid variants, especially in light of new methods of transforming allenes to diverse motifs [29][30][31][32][33][34][35][36][37