Terpenes
Terpenes are exciting natural products from several points of view. Their structure elucidation is often challenging, and also their chemical synthesis and biosynthetic investigations are difficult to perform and require special strategies. Terpenes can be used for transfer of stereochemical information in new enantioselective reagents or catalysts, or they can be of interest because of their unique bioactivities. Any article covering one or several of these aspects of terpene chemistry is welcome, regardless if it is an experimental or a theoretical study. Studies on natural products of purely terpenoid origin and on meroterpenoids are both welcome.
This thematic issue is dedicated to Prof. Kenji Mori who passed away on April 16, 2019. With him the scientific community lost one of the most eminent pheromone and terpene chemists of the past decades. Prof. Mori has published more than 1,200 scientific articles and was actively engaged in science for more than 62 years. He pioneered the importance of chirality in natural signalling compounds and was most respected for his accuracy in this field of research. Prof. Mori's work will be continued by his countless students, collaborators from academia and industry, and many researchers worldwide that have been influenced by him.
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- Published 15 Mar 2019
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Figure 1: Structures of compounds 1–8.
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Figure 2: 1H,1H COSY and key HMBC correlations of compounds 1–4 and 6.
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Figure 3: Key NOESY correlations for compounds 1–4 and 6.
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- Published 09 Apr 2019
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Figure 1: Structures of the sesquiterpene (−)-isoguaiene (1) and the trisnorsesquiterpene clavukerin A (2).
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Scheme 1: Retrosynthetic analysis for (−)-isoguaiene (1).
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Scheme 2: Synthesis of 1 by relay metathesis of trienyne 3. a) HC(OMe)3, 4 mol % LiBF4, MeOH, reflux, 80%; b)...
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Scheme 3: Attempted preparation of 1 by domino metathesis of enediyne 7. a) (i) O3, CH2Cl2, MeOH, pyridine, −...
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Scheme 4: Conversion of 28 to 1 by relay metathesis of dienediyne 8. a) (i) 21, THF, rt to reflux, (ii) BuLi,...
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- Published 30 Apr 2019
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Figure 1: Structures of the isolated metabolites bovistol A (1), its new derivatives bovistol B (2) and C (3)...
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Figure 2: Relative normalized expression of the putative sesquiterpene synthase genes going by the gene IDs A...
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- Published 02 May 2019
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Figure 1: Total ion chromatograms of hexane extracts from the incubations of HcS with A) FPP, B) GPP and C) G...
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Figure 2: Structures of HcS products arising A) from FPP together with related oxidation product 9, B) from G...
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Scheme 1: Initial steps of the cyclisation of GPP towards monoterpene products [34]. Both pathways are likely co-...
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Scheme 2: Late stage cyclisations of the himachalyl cation B to HcS products 1–6. Alternative mechanistic and...
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Figure 3: EI mass spectrum of 1 arising from an incubation of (2-2H)GPP and IPP with FPPS and HcS showing a l...
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Figure 4: Stereochemical course of the final deprotonation step towards 3, 5 and 6 investigated by GC–MS. EI ...
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Scheme 3: Proposed cyclisation mechanism towards cation B via an initial 1,11-cyclisation (path A) and an hyp...
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Figure 5: Total ion chromatogram of hexane extracts from HcS incubations with A) (R)-NPP, B) (S)-NPP and C) (...
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Figure 6: The origin of the two diastereotopic methyl groups in 1. Partial 13C NMR spectrum of A) unlabelled 1...
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Figure 7: Stereochemical course of the 1,11-cyclisation at C-1 for 7. Partial HSQC spectra of HcS incubation ...
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Figure 8: Investigation of the 1,3-hydride shift in the cyclisation towards 1. Partial 13C NMR spectra of A) ...
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Figure 9: Stereochemical course of the 1,3-hydride shift at C-10 in 1. Partial HSQC spectra of A) unlabelled 1...
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Figure 10: Position specific mass shift analysis for selected EIMS ions of HcS products. Black dots represent ...
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- Published 29 May 2019
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Figure 1: Whole-genome phylogenetic analyses of Streptomyces species. Rooted maximum likelihood phylogeny of ...
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Figure 2: Structures of the products of the ten most abundant terpene synthases in Streptomyces.
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Scheme 1: Mechanism for the cyclisation of FPP to geosmin.
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Scheme 2: Biosynthesis of 2-MIB (2). First, GPP is methylated to 14 by a SAM-dependent methyltransferase, fol...
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Scheme 3: Oxidation products derived from 3 by the cytochrome P450 monooxygenase that is genetically clustere...
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Scheme 4: Biosynthesis of cyclooctatin (20) from 7.
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Figure 3: Phylogenetic tree of geosmin synthases. Unrooted maximum likelihood phylogenetic tree of 92 geosmin...
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Figure 4: Phylogenetic tree of 2-MIB synthases. Unrooted maximum likelihood phylogenetic tree of 48 2-MIB syn...
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Figure 5: Phylogenetic tree of epi-isozizaene synthases. Unrooted maximum likelihood phylogenetic tree of 42 ...
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- Review
- Published 11 Jul 2019
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Figure 1: The reactions of aromatic PTases.
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Figure 2: The reactions catalyzed by AmbP1 (A) and AmbP3 (B).
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Figure 3: The overall structure of apo-AmbP1 (A), the Mg2+-free structure (B), and the Mg2+-bound structure (...
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Figure 4: The active site structure of AmbP1. 1 and GSPP were bound in the active site without Mg2+ (A, Mg2+-...
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Figure 5: The active site structure of AmbP3 with substrates. The AmbP3 structure in complex with hapalindole...
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Figure 6: Multiple amino acid sequence alignment of AmbP1, AmbP3, and other ABBA PTases, visualized by ESPrip...
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- Full Research Paper
- Published 13 Aug 2019
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Figure 1: The structure of the sesquiterpene lactones archangelolide (1) and trilobolide (2).
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Scheme 1: Reagents and conditions: a) MeOH, TEA, 48 h, yield 32%; b) (i) 5-azidopentanoic acid, DCC, DCM, 90 ...
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Figure 2: Intracellular localization of archangelolide-dansyl (5) in human cells from osteosarcoma (U-2 OS). ...
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Figure 3: Co-localization of dansylarchangelolide 5 with a marker of endoplasmic reticulum (top row) and with...
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Figure 4: Cartoon representation of sarco/endoplasmic reticulum Ca2+ ATPase binding pocket with A, C) archang...
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Figure 5: Molecular surface representation of sarco/endoplasmic reticulum Ca2+ ATPase binding pocket with A) ...
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Figure 6: Structural formulae of (i) thapsigargin, (ii) trilobolide (2), and (iii) archangelolide (1). Red pa...
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Figure 7: Viability of rat peritoneal cells treated with archangelolide (1), dansylarchangelolide 5 and dansy...
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Figure 8: NO production in primary rat macrophages. The cells were treated with archangelolide (1) and dansyl...
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Figure 9: Evaluation of cytokine TNF-α secretion in rat peritoneal cells. Stimulation of primary cells was in...
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Figure 10: Structure of laserolide.
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- Published 14 Aug 2019
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Figure 1: Contour plot of a HS-SPME–GC×GC–TOF–MS chromatogram (TIC) demonstrating the separation of volatile ...
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Figure 2: Sesquiterpene hydrocarbons found in the headspace of Lemberger (Vitis vinifera subsp. vinifera, clo...
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Figure 3: Detailed part of the two-dimensional contour plot (Figure 1) to demonstrate the result of a successful feed...
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Scheme 1: First steps towards the formation of sesquiterpenes. The (S)-germacradienyl cation can be formed fr...
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Scheme 2: Possible biosynthetic pathways of the sesquiterpene hydrocarbons d8-α-copaene, d8-β-copaene, d8-α-c...
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Scheme 3: Mechanistic rationale for the generation of the sesquiterpene hydrocarbons δ-cadinene (14), α-copae...
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Figure 4: MS spectra of genuine (d0) and deuterium-labeled (d6 and d8) α-cubebene (left panel) after administ...
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Scheme 4: Putative formation pathways of the sesquiterpene hydrocarbons α-ylangene (5), β-ylangene (6), β-bou...
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Figure 5: MS spectra and expected labeling patterns of A: d0-α-ylangene, B: d8-α-ylangene after administratio...
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Figure 6: Expected labeling patterns of deuterium-labeled, aromatic sesquiterpenes after administration of [6...
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Figure 7: MS spectra and expected labeling patterns of genuine and deuterium-labeled A: calamenene (isomer) a...
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Figure 8: MS spectra and expected labeling patterns of genuine (d0) and deuterium-labeled (d9) β-elemene afte...
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Scheme 5: Possible biosynthesis of d9-β-elemene, d9-(+)-valencene and d9-α-guaiene via germacrene A. *An inco...
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Scheme 6: Mechanistic rationale for the generation of the sesquiterpene hydrocarbons γ-elemene and selina-3,7...
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Figure 9: Mass spectra and associated structural formulas of d0-γ-elemene and d9-γ-elemene after administrati...
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Figure 10: MS spectra and expected labeling patterns of genuine (d0) and deuterium-labeled (d9) guaiazulene af...
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Scheme 7: Possible synthesis of d9-guaiazulene, d9-δ-elemene, d9-guaia-6,9-diene and d9-δ-selinene via germac...
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Scheme 8: Possible biosynthesis of d6-(E)-β-caryophyllene and d5-α-humulene starting from farnesyl pyrophosph...
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Figure 11: MS spectra and expected labeling patterns of d0-(E)-β-caryophyllene and d6-(E)-β-caryophyllene afte...
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- Published 23 Aug 2019
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Figure 1: Withanolides from Physalis peruviana. A) Structures of the newly characterised truncated withanolid...
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Figure 2: Key NMR correlations. (A) COSY and HMBC correlations for irinan A (2). (B) COSY and HMBC correlatio...
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Figure 3: Structures and biosynthesis of androstanes. (A) Androstane backbone and androsterone (7) as a typic...
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Figure 4: Intrinsic reactivity of 4ß-hydroxywithanolide E (1) under acidic/basic and oxidative conditions, re...
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- Published 26 Aug 2019
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Figure 1: Structures of compounds 1–12 isolated from B. sorokiniana.
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Figure 2: Key 2D NMR correlations of bipolenins K–N (1–4).
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Figure 3: Key NOESY correlations of bipolenins K–N (1–4).
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Figure 4: (a) Experimental ECD spectrum of 1 (MeOH) compared to TDDFT-calculated spectra (B3LYP-D3/def2-TZVPP...
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Figure 5: Relationship of sesquiterpenoids isolated in this study. A) Different groups of sativene/longifolen...
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- Published 28 Aug 2019
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Figure 1: Schematic diagram of the S. cerevisiae sesquiterpene overproduction platform and the products of Tv...
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Figure 2: Phylogenetic analysis of Tvi09626 with other characterised terpene synthases. Six clades are marked...
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Figure 3: GC–MS chromatogram of products in vivo (I), in yeast YZL141 (II), in vitro Tvi09626 with FPP (III),...
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Figure 4: Characterisation of Tvi09626 products. (A) Mass spectra of compound 1 at tR = 13.46 min with m/z 22...
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Figure 5: GC–MS chromatogram for the metal ion dependency assay.
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- Published 17 Sep 2019
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Scheme 1: Mechanism of the ADS-catalysed conversion of FDP (2) to amorpha-4,11-diene (3), a biosynthetic prec...
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Scheme 2: Synthesis of 8-methoxy-FDP (11) and 12-methoxy-FDP (12) (for full synthesis details see Supporting Information File 1).
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Figure 1: Total-ion chromatogram of the pentane extractable products formed in an incubation of ADS with 8-me...
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Figure 2: 1H NMR spectrum (500 MHz, CDCl3) of the 8-methoxy-γ-humulene (20) generated by ADS from 8-methoxy-F...
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Scheme 3: Potential mechanisms for the ADS-catalysed conversion of 8-methoxy-FDP (11) to 8-methoxy-γ-humulene...
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Figure 3: Total-ion chromatogram of the pentane extractable products formed in an incubation of ADS with 12-m...
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Figure 4: 1H NMR spectrum (400 MHz, CDCl3) of 12-methoxy-β-sesquiphellandrene (26) and 12-methoxyzingiberene (...
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Scheme 4: Possible mechanisms for the ADS-catalysed conversion of 12-methoxy-FDP (12) to 12-methoxy-β-sesquip...
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- Published 19 Sep 2019
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Scheme 1: Design and functional parts of the FIND technology.
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Scheme 2: Isolation of fungal strains with the FIND technology. 1. Collection of terrestrial or marine sample...
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Figure 1: Secondary metabolites isolated from H. cf. alpina.
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Figure 2: a) Significant 1H,1H-COSY and 1H,13C-HMBC correlations for compounds 1 and 2. b) Key NOESY correlat...
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- Published 02 Oct 2019
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Figure 1: CotB1 synthesizes geranylgeranyl diphosphate (GGDP) 3 from the substrates dimethylallyl diphosphate...
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Figure 2: The bacterial diterpene synthase CotB2wt·Mg2+3·F-Dola in the closed, active conformation (PDB-ID 6G...
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Figure 3: Conformational changes of CotB2 upon ligand binding. Superposition of CotB2’s open (teal), pre-cata...
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Figure 4: View into the active site of CotB2wt·Mg2+3·F-Dola [37] superimposed with CotB2wt·Mg2+B·GGSDP [36]. (A) The ...
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Figure 5: View into the active site of CotB2wt·Mg2+3·F-Dola [37]. Identical view as in Figure 4. (A) The bound F-Dola rea...
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Figure 6: The WXXXXXRY motif in protein sequences of diterpene TPS from different bacteria. Highlighted is th...
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Scheme 1: Overview of the altered product portfolio as a result of introduced point mutations in the active s...
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Scheme 2: Catalytic mechanism of CotB2, derived from isotope labeling experiments [34,35], density functional theory...
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Figure 7: (A) The inner surface of the active site is shown in gray. The bound F-Dola reaction intermediate i...
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Scheme 3: Variants of CotB2 open the route to a novel product portfolio with altered cyclic carbon skeletons,...
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- Published 31 Oct 2019
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Figure 1: Terpene constituents 1–9 found in geranium and bergamot oils and specified odours of individual com...
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Figure 2: Other selected mono- and sesquiterpenes (10–26) as fragrance materials [6].
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Figure 3: Main constituents of natural iris oil: irone (27).
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Scheme 1: First synthesis of ionone (30) [11].
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Scheme 2: First synthesis of Ambrelux (32) [14].
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Scheme 3: Industrial synthesis of myrcene (1) by pyrolysis of β-pinene (8).
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Scheme 4: First synthesis of Iso E Super® (33), Iso E Super Plus® (34) and Georgywood® (35) as a mixture of i...
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Figure 4: Iso E Super® region of GC spectra of Molecule 01 (left, 75 €–100 € per 100 mL; march 2019), a low-p...
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Scheme 5: First synthetic route to (−)-Georgywood® (35) by Corey and Hong [33].
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Scheme 6: First synthetic route to the odour-active (+)-enantiomer of Iso E Super Plus® (+)-34 [33].
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Scheme 7: Analysis of the isomerisation process and formation of products. Most importantly, Iso E Super® (33...
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Scheme 8: Isomerisation using additives such as alcohols or carboxylic acids. The product with the γ-position...
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Scheme 9: Iso E Super Plus® (34) can undergo a third cyclisation to tetrahydrofuran 59 through compound rac-53...
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Figure 5: (Adapted from ref. [8]) Ionone (30, 1893, odour threshold: 0.8 ng L−1), koavone (1982, odour threshold...
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Figure 6: Branched, terpene-like cyclohexene derivatives, that are synthetic fragrance components: 60: Iso da...
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Scheme 10: New unnatural terpenoid 70 from unnatural farnesyl pyrophosphate derivative 69 and comparison with ...
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- Published 05 Nov 2019
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Figure 1: Structures of nanangenines 1–10 isolated from A. nanangensis.
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Figure 2: Putative nanangenine biosynthetic gene cluster in A. nanangensis MST-FP2251 and homologs identified...
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Figure 3: Putative biosynthetic pathway to the nanangenines.
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- Published 28 Nov 2019
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Figure 1: Plasmodia of P. polycephalum emit a mixture of volatiles predominated by terpenoids. A) GC chromato...
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Figure 2: P. polycephalum contains four terpene synthase genes. A) Multiple sequence alignment of the protein...
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Figure 3: PpolyTPS1 and PpolyTPS4 have terpene synthase activities. A) GC chromatogram of sesquiterpenes prod...
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Figure 4: Phylogenetic analysis of PpolyTPSs with TPSs from dictyostelid social amoebae (Dictyostelids), the ...
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- Published 29 Nov 2019
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Figure 1: Examples of bioactive terpenoids.
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Figure 2: Repetitive electrophilic and nucleophilic functionalities in terpene and type II PKS-derived polyke...
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Figure 3: Abundance and distribution of bacterial terpene biosynthetic gene clusters as determined by genome ...
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Figure 4: Terpenoid biosynthesis. Terpenoid biosynthesis is divided into two phases, 1) terpene scaffold gene...
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Figure 5: Mechanisms for type I, type II, and type II/type I tandem terpene cyclases. a) Tail-to-head class I...
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Figure 6: Functional TC characterization. a) Different terpenes were produced when hedycaryol (18) synthase a...
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Figure 7: Selected examples of terpene modification by bacterial CYPs. a) Hydroxylation [89]. b) Carboxylation, h...
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Figure 8: Off-target effects observed during heterologous expression of terpenoid BGCs. Unexpected oxidation ...
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Figure 9: TC promiscuity and engineering. a) Spata-13,17-diene (39) synthase (SpS) can take C15 and C25 oligo...
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Figure 10: Substrate promiscuity and engineering of CYPs. a) Selected examples from using a CYP library to oxi...
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Figure 11: Engineering of terpenoid pathways. a) Metabolic network of terpenoid biosynthesis. Toxic intermedia...
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