Functional characterisation of twelve terpene synthases from actinobacteria

• Anuj K. Chhalodia,
• Houchao Xu,
• Georges B. Tabekoueng,
• Binbin Gu,
• Kizerbo A. Taizoumbe,
• Lukas Lauterbach and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100

• , Supporting Information File 1), suggesting that it could have a different function. The incubation with FPP yielded 7-epi-α-eudesmol (23) as the main product, besides germacrene A (24) and hedycaryol (26) that were detected by their Cope rearrangement products elemene (25) and elemol (27) formed during GC–MS

• GPP, GGPP or GFPP, but converted FPP with low product formation into varying mixtures of hedycaryol and germacrene A, detected as Cope rearrangement products 25 and 27, eventually besides acyclic products (Figure 7). According to the source organism, the enzymes were named as hedycaryol synthases (HS

• as plasticisers. A) Cope rearrangement of 24 and 26. B) Cyclisation mechanism from FPP to 23, identifying compound 26 as a biosynthetic intermediate and 24 as a side product. Terpene synthase homologs characterised in this study. Supporting Information Supporting Information File 162: Additional

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

•  56B) [103]. These complex natural compounds exhibit strong pharmacological activities like anti-inflammatory, antituberculosis, analgesic properties, etc. The key reaction steps included a highly stereoselective gold-catalyzed or thermally activated Cope rearrangement and a gold-catalyzed 6-endo-dig

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• allene 14, giving a boryl diene 16. A Cope rearrangement of the boryl diene 16 followed by transborylation gave the dienyl boronic ester 18 and regenerated the catalyst (Scheme 5). Chang reported the alkoxide-promoted hydroboration of N-heteroarenes with HBpin, the first explicit example of a B‒N/B‒H

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• conformers [26][38][39][40][41], pointing to a higher energy barrier between their conformers in comparison to the barriers between the conformers of 1. Like observed for germacrene A [40] and hedycaryol [41][42], 1 readily undergoes a Cope rearrangement to γ-elemene (5) above 120 °C (Scheme 3C), while the

• structure was subsequently secured by preparation from 1 through Cope rearrangement [20] and through dehydration of elemol (7) with POCl3 in pyridine yielding 5 and β-elemene (8) (Scheme 3D) [45]. Compound 5 has also frequently been reported from natural sources especially after heat treatment of the sample

• ), B) the four conformers of 1 established by molecular mechanics calculations (energies in black boxes are relative to 1a for which the energy was set to 0.00 kcal/mol), C) Cope rearrangement to 5 and formation from 6 by pyrolysis, D) dehydration of 7 to 5 and 8. The chemistry of germacrene B (1). A

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

• -dimethylallyl motif to 5 giving 17, followed by the anionic oxy-Cope rearrangement of the dienol into cyclohexenone 18. After desaturation, the resulting 2,5-cyclohexadienone 19 would provide a modular platform to construct the side chain of the target and analogues. Note that this updated route required the

• desired 1,2-adduct 17 in 50% yield [41]. To perform the anionic oxy-Cope rearrangement, alcohol 17 was exposed to t-BuOK, in the presence of 18-crown-6 ether (−78 °C to rt) [42]. However, these conditions did not trigger the rearrangement and the starting material was recovered. On the other hand

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• (sp3)–H allylic alkylation of 2-alkylpyridines with Morita–Baylis–Hillman (MBH) carbonates is described. A plausible mechanism of the reaction might involve a tandem SN2’ type nucleophilic substitution followed by an aza-Cope rearrangement. Various alkyl substituents on 2-alkylpyridines were tolerated

• in the reaction to give the allylation products in 26–91% yields. The developed method provides a straightforward and operational simple strategy for the allylic functionalization of 2-alkypyridine derivatives. Keywords: 2-alkylpyridines; allylic alkylation; aza-Cope rearrangement; catalyst-free

• pyridylic C(sp3)–H bond (Scheme 1b). For examples, Tunge et al. developed a Pd-catalyzed intramolecular decarboxylative coupling of heterocyclic ally esters via a tandem allylation/Cope rearrangement strategy [18]; Hartwig and co-workers reported a stereo-divergent allylic substitution with azaarene

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• major drawbacks identified with the Prins cyclization are the racemization due to competing oxonia-Cope rearrangement and side-chain exchange. Willis and co-workers studied the reactivity of the Prins reaction of different aryl group-substituted homoallylic alcohols 18 with propanal in the presence of a

• substituent at the arene ring produced predominantly symmetric THP product 26 over the desired trisubstituted heterocycle 23. The mechanism of the reaction was further investigated using enantioenriched homoallylic alcohol (S)-18 with 89% ee, which favored 2-oxonia-Cope rearrangement to give THP 23 only in 14

• propanal, which proceeded with high selectivity to give the corresponding THP 28 (79% ee, 32% yield) along with some recovered starting material (47%), as shown in Scheme 6. Partial racemization was also reported at the same time by reversible 2-oxonia-Cope rearrangement and via side-chain exchange [31][32

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• through reactions that are classified as σ-bond cleavages, α-fragmentations, inductive cleavages, McLafferty rearrangements [11], retro-Diels–Alder fragmentations [12][13], and the recently observed unusual radical-induced retro-Cope rearrangement (herein, “retro” indicates that the mass spectrometric

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• formed from hedycaryol (7) during GC/MS analysis by a Cope-rearrangement [20][21], indicating that 7 might be originally present in the hairpencils. That said, we cannot disprove that this rearrangement could also occur in the androconia. Hedycaryol is an early product of sesquiterpene biosynthesis

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

An overview of the cycloaddition chemistry of fulvenes and emerging applications

• Ellen Swan,
• Kirsten Platts and
• Anton Blencowe

Beilstein J. Org. Chem. 2019, 15, 2113–2132, doi:10.3762/bjoc.15.209

• ]. However, an alternate mechanism was proposed by Paddon-Row and Warraner [74], whereby an initial [6 + 4] cycloaddition of tropone [6π] to fulvene [4π] and subsequent Cope rearrangement produced the formal [6 + 4] adduct. More recently, Yu et al. demonstrated through computations that the initial

• cycloaddition proceeds through an ambimodal [6 + 4]/[4 + 6] transition state leading to both of the proposed [6 + 4] adducts, which can interconvert through a Cope rearrangement (Scheme 6) [107]. Dimerisation cycloadditions Generally, dimerization of fulvenes is an undesired process that may occur upon storage

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• spectrum of genuine (d0) and deuterium-labeled (d8) calamenene (isomer) as well as α-calacorene. Biosynthesis of sesquiterpene hydrocarbons via germacrene A Faraldos et al. showed that β-elemene is formed by Cope rearrangement when a solution of germacrene A in toluene is heated at reflux [36]. The

• . explaining the conversion of γ-terpinene to p-cymene [38]. May described the formation of δ-elemene from germacrene C via Cope rearrangement [32]. Considering that high temperatures are required for this reaction, our results also indicate that δ-elemene may be formed from germacrene C. The mechanisms

Synthesis of 1,2-divinylcyclopropanes by metal-catalyzed cyclopropanation of 1,3-dienes with cyclopropenes as vinyl carbene precursors

• Jesús González,
• Alba de la Fuente,
• María J. González,
• Laura Díez de Tejada,
• Luis A. López and
• Rubén Vicente

Beilstein J. Org. Chem. 2019, 15, 285–290, doi:10.3762/bjoc.15.25

• allows sigmatropic rearrangements leading to odd-numbered carbocyclic derivatives [8]. In this sense, seven-membered carbocycles, namely 1,4-cycloheptadienes, can be forthrightly prepared from cis- or trans-1,2-divinylcyclopropanes through a Cope rearrangement [8][9]. The potential of this type of

• example of isolation of these structures. Indeed, Lee and co-worker found that the corresponding gold-catalyzed reaction leads to ring-opened products through a facile oxy-Cope-rearrangement [28]. Moreover, these structures are also not accessible with metal–vinyl carbenes generated from vinyldiazo

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

• germacrene A (21) that is known to undergo a Cope rearrangement to 21a caused by the thermal impact during GC–MS analysis [38]. A 1,3-hydride shift transforms N into O that yields 22 by loss of a proton. Its reprotonation can induce a second cyclisation event via R and S to 24, or with a different

Are boat transition states likely to occur in Cope rearrangements? A DFT study of the biogenesis of germacranes

• José Enrique Barquera-Lozada and
• Gabriel Cuevas

Beilstein J. Org. Chem. 2017, 13, 1969–1976, doi:10.3762/bjoc.13.192

• into elemanes by heating through a Cope rearrangement. In some cases, these transformations are so favorable that it has been mentioned that the observed elemanes are only artifacts produced at the extraction [5][6][7][8]. It is known that 1,5-dienes suffer Cope rearrangements at temperatures between

• 200 and 300 °C, but some structural changes in the diene, such as the anionic oxy-Cope transformation allows the reactions to happen at temperatures below 0 °C [9]. The Cope rearrangement is a [3,3]-sigmatropic reaction and in general, occurs through a single transition state (TS), which has, normally

• elemanes formed via a Cope rearrangement from germacranolides only depends on the configuration of the most stable germacrane conformer since it is mainly a concerted reaction [15][18][33]. It is accepted that the conformers that normally carry out a Cope rearrangement are the ones that have crossed double

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

• based on the identification of this compound and its Cope rearrangement product β-elemene (2) formed by the thermal impact during GC–MS analysis [19] in E. coli headspace extracts under heterologous expression of the terpene synthase gene (Scheme 1). Here we present the diterpene synthase activity of

• terpene synthase from C. pinensis in its natural context remains elusive, since neither (1R,3E,7E,11S,12S)-18-hydroxydolabella-3,7-diene nor germacrene A or its Cope rearrangement product β-elemene could be detected in laboratory cultures [37]. In vitro terpene synthase activity of the investigated

• of GC–MS analyses of N. benthamiana leaf extracts. A) HdS-mit (HdS expressed with mitochondrial targeting signal) showing the production of 3 in planta, B) HdS (expression without targeting signal) and C) empty vector. Germacrene A (1) and its Cope rearrangement to β-elemene (2). Product obtained

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

• 2-hydroxy-1-indanones 111a–c (Scheme 35) [60]. The chromium η6-1,2-dioxobenzocyclobutene complex 112 could be converted into 1-indanones 113 and 114 by addition of vinyllithium derivatives, followed by a double anionic oxy-Cope rearrangement under mild conditions (Scheme 36) [61]. The derivative 114

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• bond of 71 followed by the Cope rearrangement and retro-Cope strategy previously described by the same research group [59]. The product was obtained in excellent yield, diastereo- and enantioselectivity. Later, the same authors showed a new chiral rhodium complex (R)-74 based on an analogue

• enantioselective carbenoid insertion into C(sp3)–H bond/Cope rearrangement. The reactions afforded good yields and excellent enantioselectivity. The recycling of the catalyst was evaluated in a cyclopropanation reaction and no significant decrease on its performance could be observed after five runs. Conclusion

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen–Cope rearrangement

• Qinggang Mei,
• Chun Wang,
• Zhigang Zhao,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 1220–1225, doi:10.3762/bjoc.11.135

• -prenylation of 3-O-methoxymethyl-4′-O-methyl-5-O-prenyl-7-O-benzylkaempferol (8) via para-Claisen–Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3, and the glycosylation of icaritin (3) are the key steps. Keywords: Claisen–Cope rearrangement; flavonol; icariin; prenylation; regioselectivity

• developed procedure [19]. In order to methylate exclusively the 4′-OH in kaempferol, we initially attempted to use methoxymethyl (MOM) as 7-OH protecting group, but this method could not provide an ideal yield in the 4′-OH selective methylation and in subsequent Claisen–Cope rearrangement. The resulting

• efficient method for the preparation of C-isopentenyl. In the case of flavonoids, control of the regioselectivity of ortho (C6)/para (C8)-rearranged products is still remained a challenging issue [20]. Once the prenyl ether 8 was obtained, attention was fastened on the para-Claisen–Cope rearrangement to

Attempts to prepare an all-carbon indigoid system

• Şeref Yildizhan,
• Henning Hopf and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 363–372, doi:10.3762/bjoc.11.42

• dimerized to 30, the conversion of this olefin to 14 failed. Keywords: α-methylene ketones; Cope rearrangement; cross-conjugation; indigo; McMurry coupling; Introduction Cross-conjugated organic molecules are defined as unsaturated systems containing two π-electron systems (or lone pairs) that are in

• [22][23]. The molecular packing is devoid of striking features. As far as the mode of formation of 23 is concerned, the isomerization formally is a [3.3]sigmatropic rearrangement (Cope rearrangement). Since the rearrangement of structurally similar compounds [24], including the parent system hexa-1,5

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• -Cope rearrangement of N-galactosyl-N-homoallylamines [18]. Aminooctoses, on the other hand, are present in the aminoglycoside antibiotic apramycin [19], in the form of an aminooctodiose derivative. However, only few syntheses of this dipyranoid aminosugar [20][21] were reported so far. Thus, we were

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• were inspired by the work of Miyashi, who, during the course of the investigation of the cation radical Cope rearrangement, discovered an intriguing endoperoxide-forming reaction (Scheme 1, reaction 1). Upon exposure of 1,5 and 1,6-dienes to catalytic quantities of 9,10-dicyanoanthracene (DCA) under UV

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

• the Cope rearrangement, it has to be noted that the preference of transition states (chair/boat) is opposite. Whereas the Cope rearrangement of hexa-1,5-diene 12 usually proceeds through chair-like transition state 12' (see Scheme 2) and not through the energetically disfavoured boat-transition state

• characterization of cis-divinylcyclopropane by Brown. Transition states for the Cope rearrangement and the related DVCPR. Ts = transition state. Two possible mechanisms of trans-cis isomerizations of divinylcyclopropanes. Proposed biosynthesic pathway to ectocarpene (21), an inactive degradation product of a