Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• unpleasant off-flavour [19][20]. The biosynthesis of 1 has been extensively studied. The initial hypothesis that 1 could be a degraded sesquiterpene [3] was not confirmed through isotopic labelling experiments that rather pointed to a methylated monoterpene [10][21]. Based on these experiments a biosynthetic

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

• identified by GC–MS. The characterised enzymes include a new epi-isozizaene synthase with monoterpene synthase side activity, a 7-epi-α-eudesmol synthase that also produces hedycaryol and germacrene A, and four more sesquiterpene synthases that produce mixtures of hedycaryol and germacrene A. Three

• sufficiently distant to expect novel functions, were shown to still form the same products as the previously characterised enzymes. However, the epi-isozizaene synthase from Nocardia brevifolia exhibited in contrast to the known enzyme from Streptomyces bungoensis [45] a substantial monoterpene synthase

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

• -mediated polyterpene cyclization mechanism, they proposed a rapid 9-step strategy starting from abundant monoterpene farnesol (164), chemically converted into cyclopentanol 165 bearing a trichloroketone function that is a well-known radical precursor. The authors found that the correct stereochemistry of

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

• , including the monoterpene precursor geranyl diphosphate (GPP) [1], the precursor for sesquiterpenes farnesyl diphosphate (FPP) [2], geranylgeranyl diphosphate (GGPP) towards diterpenes [3], and the sesterterpene precursor geranylfarnesyl diphosphate (GFPP) [4]. It has been demonstrated recently, that even

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• alcohol 6 with amberlyst-15® leading to the monoterpene 1. Other systems tested for the elimination of the hydroxy group in 6 were pyridinium p-toluenesulfonate (PPTS) and camphorsulfonic acid (CSA), that gave poorer results, failing to afford a single product. On the other hand, lactone 5 could also be

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• suggested to proceed through degradation of a sesquiterpene [2], but first feeding experiments with 14C-labeled acetate and methionine pointed to a methylated monoterpene [22]. Further investigations by feeding of 13C-labeled methionine and deuterated mevalonolactone isotopomers to Nannocystis exedens

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• leading to the promotion of the elimination reaction. β-Pinene isomerization β-Pinene is a bicyclic monoterpene bearing an exocyclic C=C double bond that can be recovered in large quantities from the production processes of cellulose from the wood of conifers. β-Pinene is in equilibrium with the more

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• (ΣVvdW) of the active site residues of TPSs can be easily calculated using a simple equation by Abraham and co-workers [18]. They show a clear trend, with the average values being largest for monoterpene synthases (MTPSs, ΣVvdW = 907 ± 24 Å3), and then decreasing for sesquiterpene synthases (STPSs, ΣVvdW

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• ]. The multifunctionality of CxTPS1 and CxTPS2 was only observed when the fungal TPS was expressed heterologously in E. coli and assayed in vitro whereas the fungus itself only emitted (E)-β-caryophyllene (1) when growing on agar medium. Thus, we speculate that GPP, the substrate for monoterpene

• production, is not available in Cladosporium sp. In contrast, the emission of the monoterpene α-pinene has been reported for Cladosporium cladosporioides CL-1 [66]. Interestingly, we could not detect the emission of (E,E)-α-farnesene (12), a product of the in vitro assay of CxTPS1 in our fungal cultures

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• -amino-1,3-diols, which underwent a regioselective ring closure with formaldehyde or benzaldehyde delivering pinane-condensed oxazolidines. During the preparation of 2-phenyliminooxazolidine, an interesting ring–ring tautomerism was observed in CDCl3. Keywords: 2-amino-1,2-diol; monoterpene; oxazolidin

• aminohydroxylation process starting from allylic carbamates usually carried out in the presence of potassium osmate [24][25][26][27][28]. In recent years, we have extensively studied the stereoselective synthesis, as well as catalytic and pharmacological applications of monoterpene-based 3-amino-1,2-diols, which are

• synthesize novel, cyclic potentially analogues of sphingosine, incorporating a lipophilic natural pinane skeleton, starting from commercially available monoterpene-based allylic alcohols via a stereoselective hydroxyamination in the presence of a potassium osmate(VI) catalyst. We also planned to explore the

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• monoterpene-derived pyridylphosphine ligand 58 (Scheme 10). The key step was a Kröhnke annulation reaction. The Kröhnke salt 52 was pre-synthesized from ethyl bromoacetate and pyridine and then reacted with (−)-pinocarvone (53) in the presence of ammonium acetate. The obtained keto intermediate 54 was then

• ligands. Synthesis of diphosphine pyrrole ligands. Synthesis of 4,5-diazafluorenylphosphine ligands. Synthesis of thioether-containing pyridyldiphosphine ligands starting from ethylene sulfide and diphenylphosphine. Synthesis of monoterpene-derived phosphine pyridine ligands. Synthesis of N

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• been reviewed elsewhere [3][10][11][12][13][14][15][16][17]. The first crystal structure of a monoterpene cyclase [18] was reported in 2002. Subsequently, the first crystal structures of a sesquiterpene [19][20] and a triterpene [21] cyclase were published in 1997. Less than a decade ago, the first

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

• the monoterpene linalool. There were no qualitative differences in terpenoid composition at two stages of young plasmodia. To understand terpene biosynthesis, we analyzed the transcriptome and genome sequences of P. polycephalum and identified four TPS genes designated PpolyTPS1–PpolyTPS4. They share

• 28–73% of sequence identities. Full-length cDNAs for the four TPS genes were cloned and expressed in Escherichia coli to produce recombinant proteins, which were tested for sesquiterpene synthase and monoterpene synthase activities. While neither PpolyTPS2 nor PpolyTPS3 was active, PpolyTPS1 and

• ). At the 8th day after the transfer, a total of five volatiles were detected, including three known compounds and two unidentified compounds (Figure 1A). The three known compounds are all terpenoids, including one monoterpene linalool and two sesquiterpenes (E)-β-caryophyllene and α-muurolene (Figure

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• monoterpene ether 1,8-cineole (14) and camphene (21) can be isolated from the Siberian fir needle oil. Cymbopogon oils provide among other components borneol (16b), geranyl acetate (4b) and citronellol (5). Besides limonene (6), (−)-carvone (17) is one of the main constituents in caraway oil and dill seed oil

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• synthesis of monoterpene derived ligands, we have utilized commercially available (1R)-α-pinene and (1S)-β-pinene to obtain regioisomeric exocyclic and endocyclic allylic alcohols, which were applied for the synthesis of γ-hydroxydiphenylphosphine ligands. To the best of our knowledge, only Knochel and co

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• ). CotB2 is arranged as a homo-dimer in crystallo [36][38] and it was demonstrated that CotB2 exists as a homo-dimer in solution as well [38]. The two active sites of CotB2 are arranged in an antiparallel fashion, resembling the arrangement initially observed for the monoterpene (+)-bornyl diphosphate

• synthase [47] and the sesquiterpene trichodiene synthase [48], but is in contrast to the parallel dimer as described for farnesyl diphosphate synthase [49]. Structurally, CotB2 is most closely related to the fungal monoterpene synthase aristolochene (PDB-ID 2OA6; [50]), and epi-isozizaene synthase (PDB-ID

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

• an enantiomeric mixture of monoterpenes are also known, e g., from Pinus taeda [33]. However, the major enantiomer of each cyclised monoterpene product described herein was found to be derived from (R)-A. Compound 17 was isolated from a large scale incubation of the TS with GGPP and identified by NMR

• . Proposed fragmentation mechanisms for these ions are presented in Schemes S1–S3 (Supporting Information File 1). Initial steps of the cyclisation of GPP towards monoterpene products [34]. Both pathways are likely co-occurring in the TS to explain the formation of both enantiomers of 10, 11 and 13, with the

Stereochemical investigations on the biosynthesis of achiral (Z)-γ-bisabolene in Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 789–794, doi:10.3762/bjoc.15.75

• stereochemical imprint of a TS on achiral products is not directly visible, there still can be a chiral cyclisation cascade behind these terpenes. This is true as well for examples featuring a mirror plane like the monoterpene 1,8-cineol (eucalyptol, 3), for which the absolute configuration of the intermediary

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• terpinen-4-ol (18), 1,8-cineole (13) as one of the major compounds in the extracts, and small amounts of its oxidation products 2β-hydroxy-1,8-cineole (14), 2α-hydroxy-1,8-cineole (15), 2-oxo-1,8-cineole (16) and 3-oxo-1,8-cineole (17). The monoterpene ether 13 has previously been reported from other

• Hypoxylon spp. [31] and the responsible monoterpene synthase has been identified [32]. Its hydroxylated derivatives 14 and 15 were found in insects feeding on leafs of Melaleuca alternifolia that contain large amounts of 13 [26], and both alcohols 14 and 15 along with the ketones 16 and 17 were reported as

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• activity [14][15][16]. Troponoids 3–10 have been reported in the literature in a number of natural forms (Figure 1) [1][2][3][4][5][6][7][8]. These compounds have a structural class spacing from the simple monocyclic tropones, such as the potent antifungal and antibiotic monoterpene β-thujaplicin (4) [17

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• potential of the latter two vicinal difunctionalizations of terpenoids by not only expanding their substrate scope but also by trying to achieve other bromo-oxylations as well as analogous chloro- and/or iodofunctionalizations of linear terpenoids. For this purpose, five monoterpene derivatives – bearing

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

• increase of the reactivity (86% yield), delivering the TT-linear terpene as the main product in a 16:1 ratio of 2-TT vs other dimeric isomers 2, along with Diels–Alder-generated cyclic monoterpene byproducts (Table 1, entry 4). Interestingly, the dimerization did not take place at temperatures below 90 °C

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

• applications, first and foremost in the fragrance and flavor industries, but also in the pharmaceutical and chemical industries [1][2][3]. Myrcene is a naturally occurring, acyclic monoterpene which is used industrially for the manufacture of flavoring substances and fragrances; in research it is used as a

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

• 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

• distinguished based on the labelling experiments described here. Discussion Plant and bacterial terpene cyclases show important structural differences [33]. While plant monoterpene synthases are composed of α and β domains and exhibit a quarternary α2β2 structure [34][35], bacterial mono- and sesquiterpene