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

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

• , 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

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

• higher structural complexity. It was already noticed in the 1950s by Ruzicka [9] and Barton and de Mayo [10], followed by a more detailed elaboration by Hendrickson [11], that 10-membered sesquiterpenes such as hedycaryol (3) can serve as neutral intermediates that can react upon reprotonation to 6-6

• - (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

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

• that all individuals devoid of 3 simply had no access to PAs and/or that its absence is a specific trait of I. s. derasa. In contrast, elemol/hedycaryol (8) is specific to the latter subspecies. Although sesquiterpenes are common in plants, the occurrence of a single sesquiterpene might indicate

• individual biosynthesis in this subspecies or specific take-up, because plant sesquiterpenes usually occur in mixtures. Furthermore, hedycaryol is a quite simple sesquiterpene, needing only one biosynthetic cyclization step from the universal sesquiterpene precursor farnesyl pyrophosphate (Scheme 2) [22

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

• -kaurene (16) cyclase. Functional TC characterization. a) Different terpenes were produced when hedycaryol (18) synthase and epi-cubebol (20) synthase were expressed in E. coli vs incubated with FPP (9) in vitro. b) Engineering the isoprenoid flux increases the titer of terpene production. Selected

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

• viridochromogenes DSM 40736 (accession number WP_003994861) yielded a sesquiterpene alcohol 4, that was identified as 7-epi-α-eudesmol by GC–MS [32], while GPP and GGPP were not accepted. Depending on the individual experiment, the conversion of FPP also yielded variable quantities of hedycaryol (Figure S1

• isotopic labelling experiments. The proposed biosynthesis of 7-epi-α-eudesmol (4) starts with a 1,10-cyclisation of FPP to the (E,E)-germacradienyl cation (B) which is attacked by water to form hedycaryol (4a). Its reprotonation at C-1 initiates a second cyclisation to cation C that undergoes deprotonation

• experiments give the same results. Additionally we have demonstrated that the 7-epi-α-eudesmol biosynthesis proceeds via reprotonation of the neutral intermediate hedycaryol by usage of (6-13C)FPP as substrate in an incubation experiment with recombinant purified enzyme in deuterium oxide. Finally, incubation

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

• products containing a dihydrooxepine moiety. In the case of occidenol (25, see Scheme 5), which has been isolated from the wood of Thuja koraiensis, farnesyl pyrophosphate (22) is supposed to undergo ring closure and the intermediate carbocation is trapped by hydroxide to give hedycaryol (23) [33