Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• heterocyclic terpenes by subsequent (hetero)-Diels–Alder or [4 + 1]-cycloadditions with nitrenes is also depicted. Keywords: dimerization; heterocycles; isoprene; monoterpene; palladium catalysis; Introduction The dimerization of conjugated dienes represents a useful, highly atom economic and straightforward

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

• , revealing that the expression of one and the same terpene synthase in different heterologous hosts may yield different terpene products. Keywords: biosynthesis; Chitinophaga pinensis; Nicotiana benthamiana; structure elucidation; terpenes; Introduction Terpene synthases convert a handful of simple linear

• and achiral oligoprenyl diphosphates in just one enzymatic step into a remarkable diversity of usually polycyclic structurally complex lipophilic terpenes with multiple stereogenic centres. In their active sites type I terpene synthases contain the highly conserved aspartate-rich motif DDXX(X)(D,E

• production of volatile terpenes by this bacterium that can be detected in headspace extracts [17][18]. In one of these previous reports [17] we have described a terpene synthase from Chitinophaga pinensis DSM 2588 (accession number WP_012789469) as a sesquiterpene synthase for germacrene A (1), which was

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

• Katarina Kemper Max Hirte Markus Reinbold Monika Fuchs Thomas Bruck Professorship for Industrial Biocatalysis, Department of Chemistry, Technical University of Munich, Lichtenbergstraße 4, 85748 Garching, Germany 10.3762/bjoc.13.85 Abstract With over 50.000 identified compounds terpenes are the

• , fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together

• with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

• Christian H. Hornung,
• Miguel Á. Álvarez-Diéguez,
• Thomas M. Kohl and
• John Tsanaktsidis

Beilstein J. Org. Chem. 2017, 13, 120–126, doi:10.3762/bjoc.13.15

• ’ replacement of existing, fossil resources based synthesis routes with economic alternatives based on renewable sources. Besides chemical platforms based on sugar, lignin or fatty acid containing feedstocks, terpenes present another plant derived feedstock which is of great interest for a variety of industrial

• percentages (<5%) in hops [3], celery [3], dill [9], rosemary [3], tarragon [10] and nutmeg [3] to name but a few. A review by Behr and Johnen [3] describes the manufacture of myrcene from other terpenes, as well as several synthetic routes based on this versatile and reactive starting material to form

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

• , releases a complex blend of volatiles when exposed [5]. A first analysis revealed the presence of mostly unknown terpenes, macrolides and other components in species specific compositions [5]. Detailed exploration of the function of these frog volatiles requires the analysis of the secretion and the

• species underlines the importance of macrolides for the chemical ecology of hyperoliid and mantellid frogs. On the contrary, other compounds such as the terpenes commonly found in hyperoliids remain largely unknown. Their identification and synthesis are a priority and would constitute a major step

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

• in both cases a syn addition, as could be shown by incubation of (2-13C)geranyl diphosphate in deuterium oxide. Keywords: biosynthesis; enzyme mechanisms; isotopic labelling; stereochemistry; terpenes; Introduction Among all classes of natural products the climax of structural diversity and

• ), 16.9 (1 × CH3), 15.6 (d, 2J(C,C) = 1.2 Hz, 1 × CH3) ppm; 31P NMR (202 MHz, H2O) δ −10.0 (m, 1 × P), −10.6 (m, 1 × P) ppm. Selection of achiral terpenes. Partial HSQC spectra showing the region of crosspeaks for HA and HB connected to C-3 and C-5 of A) unlabelled 1, B) (2H)-1 obtained by enzymatic

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

• ) THF (3 in Scheme 1, the general structure of which is today often as a simplification referred to as “THF diol”) [8]. In addition, they found that this reaction proceeds with high stereoselectivity (vide infra) and demonstrated that the reaction is not only limited to terpenes such as geranyl- (1b, R

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

• terpene cyclases were characterised by one- and two-dimensional NMR spectroscopic methods, allowing for a full structure elucidation. The absolute configurations of four terpenes were determined based on their optical rotary powers. Incubation experiments with 13C-labelled isotopomers of FPP in buffers

• containing water or deuterium oxide allowed for detailed insights into the cyclisation mechanisms of the bacterial terpene cyclases. Keywords: absolute configuration; biosynthesis; enzyme mechanisms; structure elucidation; terpenes; Introduction Terpenes are structurally fascinating natural products with

• 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

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

• EIMS fragmentation mechanisms of the two sesquiterpene ethers corvol ethers A and B, and the sesquiterpene alcohols epi-cubebol and isodauc-8-en-11-ol. Keywords: bacteria; isotopic labelling; mass spectrometry; reaction mechanisms; terpenes; Introduction Gas chromatography coupled to electron impact

• -methylisoborneol biosynthetic pathway by comparing the mass spectra of the methylated compounds to their non-methylated analogs [11]. Higher terpenes such as sesqui- and diterpenes, as being produced by terpene cyclases from oligoprenyl diphosphates, are usually (poly)cyclic compounds with different ring sizes

• development of structural proposals from their mass spectra impossible. Only very few studies have addressed the fragmentation mechanisms of terpenes using isotopically labelled compounds [12][13][14][15], likely because the synthesis of the required labelled material is laborious and expensive. Furthermore

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• annotation software, which means that some putative RiPP precursors are not even listed in databases. Furthermore, novel classes are difficult to identify precisely due to their novelty compared to known pathways. This is in contrast to terpenes, polyketide synthases or NRPSs, whose pathways are all clearly

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

• nitrates underwent rapid pseudohydrolysis; a process that generates corrosive nitric acid and non-volatile SOA [13]. Similar to the isoprene studies by Pye et al. the role of organic nitrates derived from terpenes is starting to gain traction. Rindelaub et al. undertook a photochemical reaction chamber

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• a striking range of molecular architectures, varying in size and complexity (Figure 1) [1][2][3][4][5]. Some terpenes sport multiple stereogenic centers and multiple carbocyclic rings. These complex hydrocarbon frameworks are derived, however, from simple precursors lacking stereogenic centers and

• transformation of reactants to products. Carbocation rearrangements that lead to terpenes Camphene, sativene and prezizaene – lifetimes and electrostatic effects Portions of the C10H17+ and C15H25+ PESs (in the absence of enzyme) relevant to the formation of camphene [21][22][78], sativene [79] and prezizaene

• [54][80] (and related terpenes) were examined in detail using several DFT methods. For each of these systems, secondary carbocations were found along reaction coordinates, but they were not minima; rather, these structures resided in regions near to TSSs for concerted reactions involving the merging

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• -catalyzed allyl–allyl cross-coupling of allylmetal species with allylic electrophiles represents one of the powerful methods to establish 1,5-dienes. These compounds are abundant in natural terpenes as well as highly versatile intermediates in organic synthesis [71][72][73]. However, highly enantioselective

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

• these experiments in combination with genetic studies, the biosynthesis of thiomarinol A (27) proceeds via coupling of 4-hydroxybutyrate to the PKS product, two cycles of chain elongation and finally coupling with the NRPS product pyrrothine. Terpenes Terpenoids constitute the largest group of natural

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• –alkyl compounds [3], olefins [4], polycyclic aromatic hydrocarbons [5], terpenes [6][7][8] and alkanes as small as ethane [9]. Over the years a number of active site mutants of P450cam have been generated by rational re-design, but the active site has not been explored in a comprehensive and systematic

Dicarboxylic esters: Useful tools for the biocatalyzed synthesis of hybrid compounds and polymers

• Ivan Bassanini,
• Karl Hult and
• Sergio Riva

Beilstein J. Org. Chem. 2015, 11, 1583–1595, doi:10.3762/bjoc.11.174

• ) Regioselective enzymatic acylation of natural products. Natural products are traditionally classified into groups of substances (terpenes, alkaloids, amino acids, lipids, etc), depending on their biosynthetic origin and on their chemical and structural features [19][20][21]. The complex structures of most of

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• fraction of starting materials for the synthesis of these compounds is still provided by the chiral pool. Usually, optically active alcohols or amino acids serve as starting material for such amine syntheses [14]. Naturally occurring terpenes such as carene [15], limonene [16], pinene [17][18] or camphor

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

• to these aspects, such as diepoxidation of limonene to the carcinogenic diepoxylimonene or oxidation of other terpenes (e.g., pinene) to harmful oxidized derivatives [14][26][27], the degradation of safrole to carcinogenic metabolites [28], or the formation of oxygentated derivatives of limonene

• sesquiterpenes, OS2/3 – oxygenated bi/tricyclic sesquiterpenes). The score plot from the PCA analysis of the O. basilicum L. essential oil compounds nanoencapsulation in β-CD (classification as acyclic or cyclic (numbered) mono- and sesquiterpenoid hydrocarbons (M and S), or the corresponding oxygenated terpenes

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

• . This publication highlights recent methods for setting quaternary and tetrasubstituted tertiary carbon stereocenters to address the synthetic hurdles encountered over many decades across multiple compound classes spanning carbohydrate derivatives, terpenes, and alkaloids. These enantioselective methods

• 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

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

• compounds with bouquets composed of up to 100 different compounds [1][2][3][4][5][6]. Major volatile classes comprise aliphatic compounds derived from fatty acid metabolism, terpenes, aromatic compounds, sulfur compounds, and pyrazines [1]. Apart from pyrazines, indole, and a few strain specific compounds

• as presented in Scheme 2. Cyclohept-4-enone (49) has recently been reported from several actinomycetes [2]. Some terpenes could be identified as well. 2-Methylisoborneol (60) and geosmin (62) are commonly produced by Streptomyces and other actinomycetes [3][30]. In addition, the sesquiterpene

• valencene (63) was found, but the amount of terpenes released is quite low compared to other streptomycetes. Some nitrogen containing trace components could not be identified. In the E- and O-extracts similarly other nitrogen containing trace components occurred, although the small amounts excluded their

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• oxidation, reduction, isomerisation or conjugation reactions [14]. Furthermore, in some bacteria assimilating terpenes as carbon sources, the first oxidation step is a P450-mediated allylic hydroxylation or allylic rearrangement reaction [15]. In vitro investigations demonstrated that P450 enzymes can

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• use of 1,3-diketone, 1,3-ketoester and 1,3-diester derivatives in retrosynthetic planning is widespread in general organic chemistry and numerous terpenes, heterocycles and steroids originate from such simple yet synthetically versatile substrates [16][17][18][19]. In contrast, despite the

[²H₂₆]-1-epi-Cubenol, a completely deuterated natural product from Streptomyces griseus

• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2841–2845, doi:10.3762/bjoc.9.319

• ; terpenes; Introduction The actinomycete Streptomyces griseus is a producer of three terpenes, 2-methylisoborneol (2-MIB, 1), (+)-caryolan-1-ol (2), and (+)-1-epi-cubenol (3, Figure 1). The biosynthesis of 2 and 3 requires the action of well characterized terpene cyclases [1][2], while the biosynthesis of

• enzyme catalysis [34], but such approaches may not be suitable for terpenes that are in many cases unstable under acidic conditions or may tend to thermal rearrangements [35]. The successful formation of a completely deuterated natural product (up to 90% 2H) by fermentation has recently been reported for

• rhamnolipids in Pseudomonas and sophorolipids in Candida apicola [36], but no examples for completely deuterated terpenes with a deuterium content of >98% as presented here are known. In conclusion, fermentation in fully deuterated medium as performed in this work may offer a good and practicable approach to

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• olefinic precursors like terpenes or terpenoids. Biocatalytic variants have a large potential for industrial applications, particularly in the pharmaceutical and food industry. Herein we report efficient biocatalytic allylic oxidations of spirocyclic terpenoids by a lyophilisate of the edible fungus

• ; natural products; terpenes; Introduction Selective oxidations of CH-bonds are attractive synthetic transformations with a broad spectrum of applications in academia and a high impact on the industrial chemical value chain as they convert relatively cheap precursors into value-added products [1][2]. Among

• these transformations, allylic oxidations are of high interest because the olefinic starting materials are readily available as cheap bulk chemicals and many interesting derivatives such as terpenes are available from renewable sources [3][4][5]. In addition, the resulting allyl alcohols [6][7][8][9][10

A concise enantioselective synthesis of the guaiane sesquiterpene (−)-oxyphyllol

• Martin Zahel and
• Peter Metz

Beilstein J. Org. Chem. 2013, 9, 2028–2032, doi:10.3762/bjoc.9.239

• the total synthesis of the anticancer guaiane (−)-englerin A. A regio- and diastereoselective Co(II)-catalyzed hydration of the olefin and a transannular epoxide opening were used as the key reactions. Keywords: asymmetric synthesis; hydration; natural products; terpenes; transannular epoxide opening