Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• the germacrene A and hedycaryol-derived carbocations. This study focused on twelve hydrocarbons derived from germacrene A and twelve from hedycaryol, which can be divided into three groups: four molecules containing 6-6 bicyclic rings, four 5-7 bicyclic compounds with the carbocation being on the

• -covalent interactions plots. Despite the structural similarities between germacrene A and hedycaryol cations, they possess a somewhat different stability trend. These differences are attributed to C+···OH intramolecular interactions present in some hedycaryol cations, which are absent in the carbocations

• derived from germecrene A. Keywords: carbocation; germacrene A; hedycaryol; stability trend; terpenes; Introduction Terpenoids form a large and highly diverse group of natural products with a wide range of usage in the pharmaceutical, cosmetic, agricultural, food, and energy industry. Among their

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• ) from Cryptosporangium arvum, and germacrene A synthase (SmTS6) from Streptomyces mobaraensis were chosen to convert four FPP analogs 72–75, which not only generated several new terpenoids (76–79), but also revealed the cyclization mechanisms of selected TSs [40] (Figure 6a). Similarly, two GGPP

• synthases, limonene synthase (CLS) and 5-epi-aristolochene synthase (TEAS). Noncanonical substrates for mechanism studies and their conversion to new terpenoids. a) New terpenoids from FPP analogs by β-himachalene synthase (HcS), (Z)-γ-bisabolene synthase (BbS), and germacrene A synthase (SmTS6). b

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

• Streptomyces pristinaespiralis [26], spiroviolene synthase from Streptomyces violens [27], micromonocyclol synthase from Micromonospora marina [28], α-amorphene synthase from Streptomyces viridochromogenes [29][30], epi-cubenol synthase from S. griseus [31], germacrene A synthase from M. marina [32], and 7-epi

• ) and the NSE triad (225NDIHSYEKE, Figure S12, Supporting Information File 1) and its closest characterised relative is with 32% identity the germacrene A synthase from M. marina [32]. The incubation with GPP resulted in minor amounts of acyclic compounds (myrcene, ocimene, linalool), while FPP gave a

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

• - (selinane) or 5-7-bicyclic (guaiane) sesquiterpenes. We have recently summarised the accumulated knowledge about sesquiterpenes derived from germacrene A (2) [12] and hedycaryol (3) [13]. Now we wish to provide a review on the known chemical space of sesquiterpenes derived from germacrene B (1) (Scheme 2

• the 13C NMR spectrum [26] indicates that the interconversion between these conformers is a fast process at room temperature. This is in contrast to the findings for germacrene A (2) and hedycaryol (3) that show strong line broadening in the NMR spectra and multiple sets of peaks for different

• 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

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• results from these experiments are contradictory. The present work reports on a reinvestigation of patchoulol biosynthesis by isotopic labelling experiments and computational chemistry. The results are in favour of a pathway through the neutral intermediates germacrene A and α-bulnesene that are both

• compound 3 and several biogenetically related terpene hydrocarbons including α-patchoulene (4), β-patchoulene (5), α-bulnesene (6) and α-guaiene (7) (Figure 1) [7]. The enzyme was subsequently made available by cDNA gene cloning, revealing germacrene A (8), α-humulene (9), (E)-β-caryophyllene (10

• . (Scheme 2) [10] DFT calculations have been performed previously by us as part of a general study on guaiane sesquiterpenes from germacrene A (8) [29]. After reprotonation of the neutral intermediate 6 to F the next cyclisation to G and Wagner–Meerwein rearrangement to D can be realised with low TS

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• pyrophosphate synthase, and GFPP geranylfarnesyl pyrophosphate. Mechanisms for type I, type II, and type II/type I tandem terpene cyclases. a) Tail-to-head class I germacrene A (13) cyclase. b) Head-to-tail type II brasilicardin (14) cyclase. c) Type II ent-copalyl diphosphate (15) synthase and type I ent

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

• (+)-valencene from germacrene A [11]. This biosynthetic pathway could also be confirmed by feeding experiments. The formation of the three aforementioned sesquiterpene hydrocarbons takes place without deuterium loss, so that with the use of d3-MVL as precursor (Scheme 5) nine deuterium atoms and with the use of

• d2-DOX six deuterium atoms were incorporated at most. This data indicates that the biosynthesis of β-elemene, (+)-valencene and α-guaiene is achieved via germacrene A. Biosynthesis of sesquiterpene hydrocarbons via (E,E)-germacrene B The mechanisms proposed by Steele et al. for the formation 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

• 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

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

• previously reported to have germacrene A synthase activity during heterologous expression in Escherichia coli, was identified by extensive NMR-spectroscopic methods as 18-hydroxydolabella-3,7-diene. The absolute configuration of this diterpene alcohol and the stereochemical course of the terpene synthase

• 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

• diterpene synthase from C. pinensis. Conclusion In this study we have reinvestigated a terpene synthase from Chitinophaga pinensis that was previously characterised as germacrene A synthase by heterologous expression in E. coli. While this result could be reproduced during the course of the present study