BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• theranostic applications. Keywords: BODIPY conjugates; cancer targeting; drug delivery; liposomes; natural compounds; sesquiterpene lactone trilobolide; Introduction Targeted (smart) drug delivery is a method for specific delivering of an active compound preferentially to some cells or tissues in the human

• describe the synthesis and application of a fluorescent construct (further called construct 6, depicted in Scheme 1) based on a green-emitting BODIPY dye and trilobolide–cholesterol (Tb-ChL) in a liposome formulation. Trilobolide (Tb, Figure 1) is a potent natural compound of the sesquiterpene lactone

• control of a number of cytokines. Alternatively, lipopolysaccharide (endotoxin) is known as strong inducer of NO in macrophages. Since it is known that sesquiterpene lactones, Tg, Tb, as well as Tb derivatives [31], possess strong stimulating activity for NO production by immune cells [40][41], we

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil

• Joyce Azzi,
• Pierre-Edouard Danjou,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2017, 13, 835–844, doi:10.3762/bjoc.13.84

• (Ner, 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol), an acyclic sesquiterpene obtained from fresh flowers of bitter orange and found in many other plants [1], is extensively used in perfumery. It was also approved by the U.S. Food and Drug Administration as a food flavoring agent and included by the

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

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

• –Alder adduct of myrcene and acrylonitrile for the use as an odorant in the perfume industry [12]. A series of Diels–Alder reactions of myrcene (1) and another sesquiterpene, farnesene, with various dienophiles have been reported by Tabor et al. [13] for the use as solvents and surfactants. The emergence

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

• 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

• -terpineol. However, in case of the sesquiterpene ethers corvol ethers A (19) and B (18) a reprotonation step was shown to proceed from the opposite face than the preceeding attack of water, thus excluding a direct proton transfer from oxygen to the neighbouring carbon (reactions from 12 to 14 in Scheme 2

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

• much later, with the first described compounds being geosmin [3] and 2-methylisoborneol [4], two irregular terpenoids that represent a degraded sesquiterpene [5] and a methylated monoterpene [6], respectively. These compounds have a musty or earthy aroma and are responsible for the smell of freshly

• cloning by homologous recombination in yeast, followed by the heterologous expression in Escherichia coli, direct headspace sampling using a closed-loop stripping apparatus (CLSA) and compound identification by GC–MS [32][33]. Here we report on the purification of six of these bacterial sesquiterpene

• relative of the enzyme from S. viridochromogenes is found in Streptomyces sp. NRRL S-481 (86% identity). Incubation of FPP with a recombinant terpene synthase from Roseiflexus castenholzii DSM 13941 (accession number WP_012119179) resulted in the formation of the sesquiterpene alcohol 2, previously

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

• incorporation rates and usually delivers a mixture of various isotopomers. We have recently synthesised all fifteen isotopomers of (13C1)farnesyl diphosphate (FPP) that can be enzymatically converted with a sesquiterpene cyclase into the corresponding labelled sesquiterpene products [16]. These enzyme products

• [16][17]. In the present study we have used the same approach to investigate the fragmentation mechanisms for corvol ethers A and B, two sesquiterpene ethers with unique carbon skeletons that are made by a terpene cyclase from Kitasatospora setae [18], and the sesquiterpene alcohols epi-cubebol and

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

• conditions (1R,5S)-(−)-85 was efficiently transformed into optically active O-nitrate ester (1R,5S)-(−)-86 in an unoptimized 80% yield (Scheme 14). The importance of this preliminary result resides in the increased awareness of the role that monoterpene and sesquiterpene nitrates have in climate chemistry

• . Research, however, on their role is, similar to IPNs, severely limited by the dearth of convenient protocols capable of generating structure and function diverse monoterpene and sesquiterpene nitrates. Finally, the kinetics and measurement of the IPNs generated within this study and their relationship to

• aspects of atmospheric chemistry have been reported [56]. Conclusion Isoprene, monoterpene and sesquiterpene nitrates are gaining recognition for their significant roles in climate chemistry however an efficient route to their synthesis has yet to be developed. Here we report an efficient silver nitrate

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• its leaves presents anti-inflammatory properties. Cyperane, guaiane, nortrixane, and trixane sesquiterpene types were reported as the main metabolites in Jungia species. This work aims to describe the isolation and identification of sesquiterpenes in the leaves of J. sellowii using liquid–liquid

• assess their antileishmanial and cytotoxic effects. To the best of our knowledge, there are no reports dealing with the isolation and structure characterization of glycosylated sesquiterpene derivatives from Jungia sellowii. Results and Discussion CPC separation The aerial parts crude extract of Jungia

• ) and the partition coefficient calculated for compounds 1 (16.20), 2 (2.77) and 3 (13.51) (Figure 1). Sesquiterpenes were previously reported from the genus Jungia [6][7][24][25][26]. Nevertheless, no glycosylated sesquiterpenes (and sesquiterpene lactones) were previously found in this genus. CPC has

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

• for formation of the sesquiterpene epi-isozizaene [96][97][98][99][100][101] (Figure 11) showed that several expected chemical steps were merged into concerted processes [80]. For example, conversion of the homobisabolyl cation to the acorenyl cation (Figure 11, step 7) is barrierless for many

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

• EIMS-fragmentation reactions of 34 by comparison of the 13C-including fragments. Singly labeled FPP isotopomers also proved valuable to investigate reprotonation steps in sesquiterpene cyclization mechanisms by incubation in deuterium oxide. The biosynthesis of the recently discovered corvol ethers A

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• several centuries its unusual property has been incredibly forgotten until 1985; when the sesquiterpene 1 (Figure 1), isolated from the leaves and flowers of the Mexican plant Lippia dulcis, resulted the main vector of sweetness that Hernández described four hundred years before in his treatise [5]. Thus

• , in honor of the Spanish scientist, this natural product was called hernandulcin [6]. Hernandulcin is the first strongly sweet sesquiterpene, making it a breakthrough discovery in the field of natural sugar substitutes. It turned out that 1, which belongs to the family of bisabolanes, is more than

• version of the synthesis published in reference [9]. First, the metallation [21] of 4 with t-BuOK and n-BuLi in hexane followed by addition of prenyl bromide (3-methyl-2-butenyl bromide) at −10 °C afforded the sesquiterpene derivative 5 ([α]D +19.5° (c 1.2, CHCl3)) in 84% yield. The VO(acac)2-catalyzed

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• Lili Yeung Lisa I. Pilkington Melissa M. Cadelis Brent R. Copp David Barker School of Chemical Sciences, University of Auckland, 23 Symonds Street, Auckland, New Zealand 10.3762/bjoc.11.215 Abstract The first total synthesis of the unusual aromatic sesquiterpene panicein A2 is reported and the

• cytotoxicity against a number of tumour cell lines. Keywords: modified Claisen rearrangement; sesquiterpene; chromenol; total synthesis; Introduction The panicein family is an unusual family of natural products, which generally consist of an aromatic sesquiterpene group linked to a quinone (as seen in

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

• increase of the relative concentration of linalool oxide from 0.3% to 1.1%, in addition to many sesquiterpene oxides, has been observed. β-CD complexation of the O. basilicum essential oil modifies the relative concentration of the encapsulated volatile compounds. Thus, linalool was better encapsulated in

• -pinene), oxygenated monoterpenes (eucalyptol, linalool, α-terpineol, borneol and its acetate), phenolic derivatives (eugenol, methylchavicol (estragole)), sesquiterpene hydrocarbons (β-cubebene, β-caryophyllene, germacrene, etc.), and oxygenated sesquiterpenes (cadinol, spathulenol) [9][16][20][25

• sesquiterpene derivatives in the O. basilicum L. essential oil. Some of degradation compounds (mainly a result of the separation process) can also be identified in the raw O. basilicum L. essential oil sample, such as caryophyllene oxide (17) (0.4%), aristolene oxide (21) (0.3%), aromadendrene oxide (23) and

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

• 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

• methylisoborneol are typical terpenes of the actinomycetes. Various sesquiterpene cyclases occur in the streptomycetes [3][30][32] and give rise to a wide variety of sesquiterpenes, in this case valencene. The only strain specific compounds are the streptopyridines. They have not been reported from other strains

New sesquiterpene hydroquinones from the Caribbean sponge Aka coralliphagum

• Qun Göthel and
• Matthias Köck

Beilstein J. Org. Chem. 2014, 10, 613–621, doi:10.3762/bjoc.10.52

• Qun Gothel Matthias Kock Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung, Am Handelshafen 12, 27570 Bremerhaven, Germany 10.3762/bjoc.10.52 Abstract Four new sulfated sesquiterpene hydroquinones siphonodictyals E1–E4 (1–4) and cyclosiphonodictyol A (5) were isolated from

• ; natural products; NMR; sesquiterpene hydroquinone; structure elucidation; Introduction Aka coralliphagum (Siphonodictyon coralliphagum) is known to have four distinct morphological forms: forma typica, f. tubulosa, f. obruta, and f. incrustans [1]. This sponge has the ability to burrow into live coral

• viscous mucus containing the toxic secondary metabolites which are produced by the sponge tissue [3]. This ecological observation inspired the chemical investigation of this sponge by different research groups. Thus many secondary metabolites have been reported, such as the sesquiterpene phenolic

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

• furnished scopadulcic acid B (79). A similar approach was used by the same group in their total synthesis of scopadulcic acid A [81]. Davies and coworkers [82] utilized the DVCPR embedded in a formal [4 + 3]-cycloaddition [83] in the total syntheses of the related sesquiterpene metabolites tremulenolide A

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

• I. Wayan Mudianta,
• Victoria L. Challinor,
• Anne E. Winters,
• Karen L. Cheney,
• James J. De Voss and
• Mary J. Garson

Beilstein J. Org. Chem. 2013, 9, 2925–2933, doi:10.3762/bjoc.9.329

• obtained by preparative enantioselective HPLC. Keywords: enantioselective HPLC; E/Z-isomers; Hypselodoris; natural products; nudibranch; sesquiterpene; Introduction Marine organisms have been proven a prolific source of natural products that potentially can be used as lead compounds or which have

• sesquiterpene chemistry, as evidenced by a number of studies on European [7][8][9][10][11][12][13], Indian [14], South African [15], Brazillian [16], and Indo-Pacific specimens [17][18][19][20]. During a comparative biogeographical study on opisthobranch molluscs from South East Queensland, Australia, we

• encountered the new sesquiterpene (−)-(5R,6Z)-dendrolasin-5-acetate (1) in specimens of H. jacksoni along with the other known sesquiterpene metabolites (+)-agassizin, (−)-furodysinin, (−)-euryfuran, (−)-dehydroherbadysidolide, (+)-pallescensone. The new metabolite 1 has never been identified from natural

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• production of inhibitors of survivin promoter activity, a new drimane sesquiterpene lactone, SF002-96-1, was isolated from fermentations of an Aspergillus species. The compound inhibited survivin promoter activity in transiently transfected Colo 320 cells in a dose dependent manner with IC50 values of 3.42

• attractive target for new anticancer therapeutics [13]. In a search for new inhibitors of survivin expression from natural sources, we found that cultures of Aspergillus sp. strain IBWF002-96 produced a new drimane sesquiterpene lactone, SF002-96-1, with inhibitory activity on survivin promoter activity in

• methylene protons at δ 4.23 and 4.48 and the carbons at δ 44.6, 77.0, 133.8, and 169.8 suggested SF002-96-1 to be a drimane sesquiterpene (Figure 1). The proton signals of the methyl group (δ 0.87), four methylene groups (δ 1.28, 1.30, 1.59 and 2.32) and a carbonyl group (δ 173.5) constituted an n-hexanoyl

[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

• because of the high deuterium content. Deuterated 3 eluted almost 1 min earlier than unlabeled epi-cubenol. Its mass spectrum obtained after growth on DMM in comparison to the natural compound revealed a shifted molecular ion from m/z = 222 for the sesquiterpene alcohol 3 (C15H260) to m/z = 248 for

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

• ; Introduction The hydroazulene framework is present in many natural products that are often associated with interesting biological properties [1][2]. The guaiane sesquiterpene (−)-oxyphyllol (1) has been isolated from the roots of the Thai medicinal plant Phyllanthus oxyphyllus [3]. A recent enantioselective

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• ] that crystals of the sesquiterpene santonin would literally burst open upon exposure to sunlight can perhaps be considered as the beginning of organic photochemistry. In 1883 Cannizzaro and Sestini [2] investigated this further and reported the formation of photosantonic acid upon irradiation of

The volatiles of pathogenic and nonpathogenic mycobacteria and related bacteria

• Thorben Nawrath,
• Georgies F. Mgode,
• Bart Weetjens,
• Stefan H. E. Kaufmann and
• Stefan Schulz

Beilstein J. Org. Chem. 2012, 8, 290–299, doi:10.3762/bjoc.8.31

• fatty-acid derivatives were released by pathogenic/nonpathogenic mycobacteria, while the two Nocardia spp. (N. asteroides and N. africana) emitted the sesquiterpene aciphyllene. Pathogenic Mycobacterium tuberculosis strains grown on agar plates produced a distinct bouquet with different volatiles, while

• from M. tuberculosis. While the mycobacteria grown on the 7H11 solid medium emitted a wide variety of volatiles, Nocardia asteroides produced, even in different ages, only 4-pentanolide (10) (Table 3). Additionally, N. africana also released only one compound, the sesquiterpene aciphyllene (19), which

One-pot four-component synthesis of pyrimidyl and pyrazolyl substituted azulenes by glyoxylation–decarbonylative alkynylation–cyclocondensation sequences

• Charlotte F. Gers,
• Julia Rosellen,
• Eugen Merkul and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2011, 7, 1173–1181, doi:10.3762/bjoc.7.136

• , such as Friedel–Crafts-type reactions, generally occurs in the 1-position [24]. Interestingly, the azulene motif is also found in terpenoids [27][28]. Guaiazulene (1b) (Scheme 1), a commonly known derivative of azulene (1a), is a naturally occurring sesquiterpene [29]. Guaiazulene (1b) has found entry

• -component approach to heterocyclic derivatives of azulene is well suited for the development of functional chromophores with extended π-conjugation. Selected resonance structures of azulene (1a) and structure of the sesquiterpene guaiazulene (1b). Synthesis of ynones by glyoxylation–decarbonylative

A racemic formal total synthesis of clavukerin A using gold(I)-catalyzed cycloisomerization of 3-methoxy-1,6-enynes as the key strategy

• Jae Youp Cheong and
• Young Ho Rhee

Beilstein J. Org. Chem. 2011, 7, 740–743, doi:10.3762/bjoc.7.84

• sesquiterpene natural products. It was first isolated in 1983, by the group of Kitawara, from the Okinawa soft coral Clavularia koellikeri. The structure of clavukerin A was established by CD spectra and X-ray diffraction [1]. The first total synthesis of clavukerin A was reported by Asaoka in 1991, which was