Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• depends on the precursors that these synthases can accommodate: geranyl diphosphate (monoterpenes, C10), farnesyl diphosphate (sesquiterpenes, C15) and geranylgeranyl diphosphate (diterpenes, C20). The biological function of terpenes is best studied for plants where they play important roles in

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• truncatula with at least 27 products [7], γ-humulene synthase from Abies grandis with 52 products [8], and also the long known trichodiene synthase from Fusarium sporotrichioides produces at least 15 sesquiterpenes [9]. Some TSs can even accept multiple chain length substrates [10], a concept which seems to

• . Whereas the latter diphosphate did not lead to any terpene product, the incubation with FPP showed a smooth conversion into several sesquiterpenes (Figure 1A) with compound 1 as the major peak after GC–MS analysis. However, also the incubations with GPP (Figure 1B) and GGPP (Figure 1C) led to several less

• Information File 1). Taken together, the overall more sluggish conversion of GPP and GGPP by the TS leading to enantiomeric mixtures, the higher biosynthetic complexity of the obtained sesquiterpenes and the absence of spontaneous hydrolysis products in the incubation with FPP compared to the appearance of 14

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

• II into solanapyrone [18]. A similar cycloaddition is needed to form bovistol out of two illudine precursors. Although the respective illudine has not been detected in this study, it is known that C. aegerita is able to produce several illudanes [11]. As proposed in recent studies on sesquiterpenes

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

• compounds [1][2][3][4]. A variety of structurally unique sesquiterpenes, including aromadendranes [5], maalianes [5], elemanes [6], and trinor-guaianes [7][8][9], have been isolated since the early 1980s from several species of Clavularia. Soft corals of the genus Lemnalia are also a rich source of

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• I TSs (349DEFME and 847NDYGSLARD). Furthermore, two groups of structurally and biosynthetically related sesquiterpenes were found that could each arise from one sesquiterpene synthase (STS). The first of these groups comprised the main compound α-acoradiene (15), accompanied by minor amounts of β

• -sesquiphellandrene (8), ar-curcumene (9), β-bisabolene (10), (E)-γ-bisabolene (11), trans-α-bergamotene (12), δ-cuprenene (13), and cuparene (14). All these sesquiterpenes arise through a 1,6-cyclisation of farnesyl diphosphate (FPP, via nerolidyl diphosphate, NPP) to the bisabolyl cation (A, Scheme 2). A mixture of

• sesquiterpenes arising via cation A with the main product trichodiene was previously reported from Fusarium [34]. The compounds 10 and 11 are directly formed from this cation by deprotonation. A 1,3-hydride shift to B and deprotonation yields 8 and γ-curcumene (C). Instead of the latter compound its autoxidation

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• mass spectrum and the retention index match reported data. The comparison of retention indices is particularly important, if different stereoisomers need to be considered, because stereoisomers may have very similar mass spectra, as observed for the sesquiterpenes α-muurolene (3), α-amorphene (4), and

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• resemblance to cadinane-type sesquiterpenes from plants, but is structurally entirely unprecedented in bacteria. Based on its molecular architecture, a possible biosynthetic pathway is postulated. Keywords: genome mining; herpetopanone; Herpetosiphon; isotope labeling; terpene; Introduction Terpenoids

• NMR data for 2 [22] confirmed our assignment of the octahydro-1H-indene skeleton. The biosynthesis of the bicyclic ring system in 2 was previously proposed to occur via an α-cadinol intermediate, which undergoes a ring contraction reaction [19]. The cadinane family of sesquiterpenes, which also

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• ion at m/z = 290 pointing to a diterpene alcohol and a base peak ion at m/z = 59 indicative of a 2-hydroxyisopropyl group that frequently occurs in terpene alcohols. Both findings, i.e., no production of sesquiterpenes from FPP in in vitro experiments with recombinant purified enzyme as well as the

• emission of sesquiterpenes by E. coli during heterologous expression, were fully reproducible (Figure S2, Supporting Information File 1). The compound 3 obtained from the in vitro incubation of GGPP was purified and its structure was elucidated by extensive one- and two-dimensional NMR spectroscopic

• recombinant enzyme from C. pinensis, showing no formation of monoterpenes from GPP (A) and no formation of sesquiterpenes from FPP (B), but formation of a single diterpene alcohol 3 from GGPP (C) with the mass spectrum depicted in (D). Asterisks indicate non-terpenoid contaminants such as plasticisers

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

• , GPP, the universal precursor for all monoterpenes [40]. Subsequent cis-addition of further IPP-units to geranyl diphosphate by farnesyl diphosphate synthase (FPPS) and geranylgeranyl diphosphate synthase (GGPPS) yield in the respective precursors for sesquiterpenes (farnesyl diphosphate, FPP) and

Identification, synthesis and mass spectrometry of a macrolide from the African reed frog Hyperolius cinnamomeoventris

• Markus Menke,
• Pardha Saradhi Peram,
• Iris Starnberger,
• Walter Hödl,
• Gregory F.M. Jongsma,
• David C. Blackburn,
• Mark-Oliver Rödel,
• Miguel Vences and
• Stefan Schulz

Beilstein J. Org. Chem. 2016, 12, 2731–2738, doi:10.3762/bjoc.12.269

• , Institute of Zoology, 38106 Braunschweig, Germany 10.3762/bjoc.12.269 Abstract The contents of the gular glands of the male African reed frog Hyperolius cinnamomeoventris consist of a mixture of aliphatic macrolides and sesquiterpenes. While the known macrolide gephyromantolide A was readily identified

• Hyperolius cinnamomeoventris showed the presence of several unknown compounds, sesquiterpenes and macrolides (Figure 2). Gephyromantolide A (5), known from the mantellid frog Gephyromantis boulengeri [4], was readily identified. A second macrolide (A in Figure 2) showed a mass spectrum similar to that

A detailed view on 1,8-cineol biosynthesis by Streptomyces clavuligerus

• Jan Rinkel,
• Patrick Rabe,
• Laura zur Horst and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 2317–2324, doi:10.3762/bjoc.12.225

• and achiral precursors such as geranyl diphosphate (GPP, monoterpenes), farnesyl diphosphate (FPP, sesquiterpenes) and geranylgeranyl diphosphate (GGPP, diterpenes). Terpene cyclases (type I) contain a trinuclear (Mg2+)3 cluster in their active site that is stabilised by binding to several highly

• representing various stereoisomers and constitutional isomers with different positioning of olefinic double bonds or alcohol functions are known just for sesquiterpenes [11]. The structural diversity of terpenoids can be further increased by the action of tailoring enzymes such as cytochrome P450

• monooxygenases and acyl transferases [12][13]. Very few cases are known in which terpene cyclases generate an achiral product as exemplified by the monoterpene 1,8-cineol (eucalyptol, 1) and the sesquiterpenes germacrene B (2) and α-humulene (3) (Figure 1). A direct 1,6-cyclisation of the monoterpene precursor

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• citrus fruits. Cineol is one of the main constitutents of eucalyptus oil and (+)-carvone is present in caraway. Some famous sesquiterpenes are α-humulene from hops, α-patchoulene from patchouli oil, and β-cedrene from juniper [1]. Only a minority of terpenes such as cineol and α-humulene are achiral, and

• strict stereochemical course for the FPP cyclisation, as is reported for most, but not all other terpene cyclases that were investigated for this aspect. It is interesting to note that the bacterial sesquiterpenes identified in this study are in most cases the opposite enantiomers as known from plants

• mg to 3.0 mg in 2 mL 2H2O or H2O) at 28 °C overnight. The reaction mixture was extracted with 2 × 0.4 mL (2H6)benzene and directly measured by NMR. Structures of sesquiterpenes obtained by incubation of FPP with bacterial sesquiterpene cyclases. Contiguous spin systems observed by 1H,1H-COSY (bold

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• of triarylmethanols 159a–d [299]. The successive insertion of oxygen atoms gave rise to diaryl carbonates 160a–d in good yields (Scheme 47). In the last years, new enantiospecific approaches for the synthesis of sesquiterpenes 162 from ketone 161 were developed [301][302][303][304][305][306][307]. In

The EIMS fragmentation mechanisms of the sesquiterpenes corvol ethers A and B, epi-cubebol and isodauc-8-en-11-ol

• Patrick Rabe and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1380–1394, doi:10.3762/bjoc.12.132

• studies with (1(10)E,4E,6S,7R)-germacradien-6-ol synthase from Streptomyces pratensis and epi-isozizaene synthase from Streptomyces albus, that the enzymatically obtained products from the (13C1)FPP isotopomers are useful for detailed investigations on the EIMS fragmentation mechanisms of sesquiterpenes

• the investigated sesquiterpenes some of the fragment ions in their mass spectra clearly increased by +1 amu, indicating that the corresponding carbon atom contributes to the fragment ion, while for other fragment ions no such increase was observed, showing that the respective labelled carbon is

• substrates to polycyclic terpenes with usually several stereocentres [24][25][26][27][28]. We have demonstrated here, how isotopic labelling experiments can be used to investigate the EIMS fragmentation mechanisms of structurally complex sesquiterpenes. This field was initiated in the 1960s with main

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• [2], however, many other different types of biogenic volatile organic compounds (BVOCs) are also generated and released. These include monoterpenes, e.g., 1,8-cineole, borneol, β-phellandrene, 2-carene, camphene, sabinene and citral; sesquiterpenes, e.g., α-copaene, β-cubebene, α-cedrene, β-selinene

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

• its leaves presents anti-inflammatory properties. Cyperane, guaiane, nortrixane, and trixane sesquiterpene types were reported as the main metabolites in Jungia species. This work aims to describe the isolation and identification of sesquiterpenes in the leaves of J. sellowii using liquid–liquid

• better separation, and it was used in the CPC equipment (details described in the experimental section) from which three new glycosylated sesquiterpenes were achieved in a single run in less than two hours (Figure 1). The compounds were identified to be two trixanolides and one guaianedienone (Figure 2

• ) and the partition coefficient calculated for compounds 1 (16.20), 2 (2.77) and 3 (13.51) (Figure 1). Sesquiterpenes were previously reported from the genus Jungia [6][7][24][25][26]. Nevertheless, no glycosylated sesquiterpenes (and sesquiterpene lactones) were previously found in this genus. CPC has

Natural products from microbes associated with insects

• Christine Beemelmanns,
• Huijuan Guo,
• Maja Rischer and
• Michael Poulsen

Beilstein J. Org. Chem. 2016, 12, 314–327, doi:10.3762/bjoc.12.34

• )), sesquiterpenes with an unprecedented carbon skeleton that are most likely built up by an enzymatic Aldol addition. In a similar example, new cytotoxic furanone analogues (e.g., paraconfuranone A (39)) were obtained from the fungus Paraconiothyrium brasiliense isolated from the gut of the grasshopper Acrida

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• cyclononene framework (Figure 3). For example, a class of bicyclic sesquiterpenes, caryophyllenes [21], exhibit the same bicyclo[7.2.0]undecane skeleton as xeniaphyllanes. Furthermore, while monocyclic azamilides [22] are seco-A-ring diterpenoids that are acylated with fatty acids, Dictyota diterpenes [23][24

• structurally related caryophyllene sesquiterpenes [25]. Xenia diterpenoids are believed to originate from the common diterpenoid precursor geranylgeranyl pyrophosphate (GGPP, 28), which is assembled from the two terpene units, isoprenyl pyrophosphate (IPP, 26) and dimethylallyl pyrophosphate (DMAPP, 27) [26

• in 1% overall yield (Scheme 16). In addition to the presented strategies for the synthesis of Xenia diterpenoids, total syntheses of the Xenia sesquiterpenes xenitorin B and C were also reported [71]. Conclusion This review has presented various synthetic approaches towards xenicane and xenicane

Recent highlights in biosynthesis research using stable isotopes

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2015, 11, 2493–2508, doi:10.3762/bjoc.11.271

• interesting insights into terpene synthase catalyzed cyclizations. Labeled oligoprenyl diphosphates, the substrates for these enzymes, can be made available by synthesis and provide an excellent tool for such investigations, as recently demonstrated for sesquiterpenes by the synthesis of all 15 singly 13C

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• reagent. The taste evaluations indicate that none of these sesquiterpenes are sweet, instead the lippidulcine A is a cooling agent with a mint after taste. Keywords: ADH ketone reduction; cooling agent; Corey–Bakshi–Shibata reduction; dehydrogenation; hernandulcin; Kornblum–DeLaMare rearrangement

• 1000 times as sweet as sucrose. More recently other derivatives of 1 have been discovered, i.e., the peroxylippidulcines 2a–c and the lippidulcines 3a–c (Figure 1) [7][8]. However, these sesquiterpenes have been isolated in a so small amount that it has not been possible to assess their taste. In

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

• -pinene), oxygenated monoterpenes (eucalyptol, linalool, α-terpineol, borneol and its acetate), phenolic derivatives (eugenol, methylchavicol (estragole)), sesquiterpene hydrocarbons (β-cubebene, β-caryophyllene, germacrene, etc.), and oxygenated sesquiterpenes (cadinol, spathulenol) [9][16][20][25

• . essential oil composition Ocimum basilicum L. essential oil contains many volatile compounds comprised of monoterpenes, oxygenated monoterpenes, sesquiterpenes and their oxygenated derivatives, as well as phenolic derivatives (Figure 1 and Table 1). The most important constituents were linalool (4) (27.8

• ) and carvone (7). On the other hand, sesquiterpenes were more abundant in the O. basilicum L. essential oil samples in comparison with their oxygenated derivatives. The quantified sesquiterpenes were 17.1%, while the oxygenated sesquiterpenes were in a relative concentration of 8.4%. The most important

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

• used for centuries as decoration and within traditional architecture [17]. The plant is a member of the order Cupressaceae, and its fragrant wood oil contains numerous sesquiterpenes including mayurone (8) [18][19], widdrol (9) [20], and (−)-thujopsene (10) (Figure 1) [21][22]. The wood oil is a potent

Streptopyridines, volatile pyridine alkaloids produced by Streptomyces sp. FORM5

• Ulrike Groenhagen,
• Michael Maczka,
• Jeroen S. Dickschat and
• Stefan Schulz

Beilstein J. Org. Chem. 2014, 10, 1421–1432, doi:10.3762/bjoc.10.146

• methylisoborneol are typical terpenes of the actinomycetes. Various sesquiterpene cyclases occur in the streptomycetes [3][30][32] and give rise to a wide variety of sesquiterpenes, in this case valencene. The only strain specific compounds are the streptopyridines. They have not been reported from other strains

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

• coralliphagum are bicyclic sesquiterpene hydroquinones. However, in the course of our investigation, three linear sesquiterpenes were isolated. From a biosynthetical point of view [11], we propose that the linear sesquiterpenes are the precursors of the bicyclic sesquiterpenes (Figure 8). Therefore

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