Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• [4]. Oxygen heterocycles are mainly found in carbohydrates, polyketides, peptides and terpenoids. Nitrogen heterocycles are part of peptides and alkaloids. Both can of course also occur in the respective hybrid natural products. Sulphur-containing heterocycles are present in few polyketides and more

• [138][139]. With the exception of a few terpenoids, most tetronates are of polyketide origin, either being completely biosynthesised by a PKS or by hijacking intermediates from fatty acid biosynthesis (Figure 6). Although the larger body of tetronates is produced by Actinobacteria, they are abundant in

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• solvents upon light exposure [62]. The salimyxins represent the third group of compounds, i.e., salimyxin A (29) and B (30). These belong to a subgroup of terpenoids named incisterols, which were first discovered from the sponge Dictyonella incisa [63]. Their biosynthesis presumably involves oxidative

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

• the polyphenols identified in Jungia species, sesquiterpenoids with guaiane, guaiene, nortrixane, trixane (isocedrene), and cyperane scaffolds are also representative of this genus [6][7][8][9]. These terpenoids demonstrated a wide range of bioactivities [10][11][12], and hit compounds such as

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• nine-membered carbocycle which is the characteristic structural feature of these natural products. Additionally, the putative biosynthetic pathway of xenicanes is illustrated. Keywords: asymmetric synthesis; natural products; total synthesis; Xenia diterpenoids; xenicanes; Introduction Terpenoids are

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

• classes including polyketides, non-ribosomal peptides, their hybrids, terpenoids, and aromatic compounds formed via the shikimate pathway. The text does not aim at a comprehensive overview, but instead a selection of recent important examples of isotope usage within biosynthetic studies is presented, with

• these experiments in combination with genetic studies, the biosynthesis of thiomarinol A (27) proceeds via coupling of 4-hydroxybutyrate to the PKS product, two cycles of chain elongation and finally coupling with the NRPS product pyrrothine. Terpenes Terpenoids constitute the largest group of natural

• rearrangements and cyclizations experimentally. The structure elucidation of terpenoids can be challenging because of the multicyclic carbon skeletons with several contiguous stereocenters. The assistance of 13C labels can in such cases be especially helpful, and if completely 13C-labeled carbon backbones can be

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• , terpenoids, phenolics, polysaccharides and alkaloids [4]. Various bioactivity functions such as anticancer [5][6][7], phytotoxicity [8][9][10][11], antioxidant [12][13][14][15][16], antimicrobial [17][18][19], analgesic [20][21], hypotensive [22], hypoglycemic [23], antiprotozoal [24] and plant protecting

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• , in Pd catalysts. Keywords: chirality; hydrolysis; phosphorus; rearrangements; terpenoids; Introduction Phosphorus halides are highly reactive intermediates for the synthesis of phosphites and phosphoramidites [1][2][3][4][5], which are widely used, for example, as ligands in catalysts [6][7][8][9

Stereoselective cathodic synthesis of 8-substituted (1R,3R,4S)-menthylamines

• Carolin Edinger,
• Jörn Kulisch and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 294–301, doi:10.3762/bjoc.11.34

• naturally occurring terpenoids is the reductive amination under Leuckart–Wallach conditions (see Scheme 2, pathway I) [39]. This method was applied to convert 2 to N-alkyl substituted menthylamines [40]. However, a significant disadvantage of this method is the lack of stereocontrol and partial inversion of

Synthesis of the furo[2,3-b]chromene ring system of hyperaspindols A and B

• Danielle L. Paterson and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 265–270, doi:10.3762/bjoc.11.29

• been isolated from H. chinense including prenylated acylphloroglucinols such as chinesins I (3) and II (4), xanthones, flavonoids, terpenoids, naphthodianthrones, and norlignans, such as hyperione A (5) and B (6) [1][6][7][8]. Chinesins I (3) and II (4) are acylphloroglucinol derivatives which possess

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

• Soyoon Baek,
• Xuikui Xia,
• Byung Sun Min,
• Chanil Park and
• Sang Hee Shim

Beilstein J. Org. Chem. 2014, 10, 2955–2962, doi:10.3762/bjoc.10.313

• pain, and retained lochia due to stasis [4]. Recent studies have indicated that Trogopterus feces mainly consist of terpenoids [5][6][7][8][9], phenolic acids, sterols, aliphatics, fatty acids, and flavonoids [10][11]. They have been reported to possess various pharmacological properties such as

Total synthesis of the proposed structure of astakolactin

• Takayuki Tonoi,
• Keisuke Mameda,
• Moe Fujishiro,
• Yutaka Yoshinaga and
• Isamu Shiina

Beilstein J. Org. Chem. 2014, 10, 2421–2427, doi:10.3762/bjoc.10.252

• sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson–Claisen rearrangement, asymmetric Mukaiyama aldol reaction and MNBA-mediated lactonization. Keywords: aldol reaction; astakolactin; lactonization; MNBA; terpenoids; Introduction

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

• polyketides, nonribosomal peptides, terpenoids, alkaloids, lipids and others. Such compounds became a major source of biologically active natural products as antibiotics, cytotoxic compounds, immunosuppressants etc. In addition, actinomycetes are also able to produce and release a wide variety of volatile

Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• YX that enables this type of oxidation. Several acyclic terpenoids were tested as possible substrates for CYP154E1, and the regio- and chemoselectivity of their oxidation was investigated. Using a previously established bioinformatics approach we identified position 286 in the active site of CYP154E1

• -box for allylic hydroxylation in synthetic chemistry. Keywords: allylic hydroxylation; cytochrome P450; natural products; protein engineering; regiochemistry; terpenoids; Introduction Direct allylic hydroxylation yielding highly valuable allylic alcohols has been recognised for a while as one of the

• terpenoids in plants represents the most prominent example [14]. Heme-containing cytochrome P450 monooxygenases (P450 or CYP) are predominantly responsible for structural and functional diversity of terpenoids: allylic hydroxylation of parental monoterpenes leads to further diversification via sequential

[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

• splitless (60 s valve time) and the carrier gas was He at 1.2 mL min−1. The GC was programmed as follows: 5 min at 50 °C increasing with 5 °C min−1 to 320 °C. Retention indices (I) were determined from a homologous series of n-alkanes (C8–C38). Terpenoids from Streptomyces griseus. Total ion chromatograms

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• olefinic precursors like terpenes or terpenoids. Biocatalytic variants have a large potential for industrial applications, particularly in the pharmaceutical and food industry. Herein we report efficient biocatalytic allylic oxidations of spirocyclic terpenoids by a lyophilisate of the edible fungus

• Pleurotus sapidus. This ‘’mushroom catalysis’’ is operationally simple and allows the conversion of various unsaturated spirocyclic terpenoids. A number of new spirocyclic enones have thus been obtained with good regio- and chemoselectivity and chiral separation protocols for enantiomeric mixtures have been

• several functionalized terpenoids (Figure 1) [32]. Biocatalytic allylic oxidations with PSA may be performed with the lyophilisate from submerged cultures. Cyclic alkenes and particularly cyclohexene derivatives are the preferred substrates of PSA. A PSA-derived dioxygenase has been shown to be

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• copper(II) triflate-catalyzed Ullmann coupling furnished 136. Meroterpenoids: The term meroterpenoids describes a family of natural products with a mixed biosynthetic origin, partially derived from terpenoids and polyketides [129]. Several members of this class containing an isoindolinone motif, for

Lanostane- and cycloartane-type triterpenoids from Abies balsamea oleoresin

• Serge Lavoie,
• Charles Gauthier,
• Jean Legault,
• Sylvain Mercier,
• Vakhtang Mshvildadze and
• André Pichette

Beilstein J. Org. Chem. 2013, 9, 1333–1339, doi:10.3762/bjoc.9.150

• -lanostane triterpenoids 1–3, one new cycloartane triterpenoid 4 along with fourteen known terpenoids. Structure determinations were based on extensive 1D/2D NMR, IR and MS spectroscopic analyses, and comparison with literature data. The isolated compounds were evaluated in vitro for their cytotoxicity

• ]. Since then, more than 277 secondary metabolites have been isolated, and mainly identified as terpenoids, flavonoids and lignans [3]. Balsam fir Abies balsamea (L.) Mill., a popular Christmas tree in Canada, has been used traditionally by North American aboriginal people as an antiseptic, tuberculosis

• triterpenoid 4 and fourteen known terpenoids. The antibacterial (E. coli and S. aureus) and cytotoxic (A549, DLD-1 and WS1) activities of the isolated compounds are also reported. Results and Discussion The oleoresin of A. balsamea (1st lot) was fractionated by silica gel column chromatography with hexanes

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• endohyperparasitoid wasp, Alloxysta victrix, we identified several acyclic terpenoids and the trans-fused (4S,4aR,7R,7aS)-dihydronepetalactone (X) as volatile components of cephalic secretions released by this species (Figure 1) [1][2]. However, gas chromatograms showed the presence of two additional major volatiles

• details see Supporting Information File 1. Strategy for the stereoselective synthesis of trans-fused iridomyrmecins A–D from (R)-limonene. Configurations of the trans-fused iridomyrmecins A and B’. Configurations of the trans-fused iridomyrmecins C and D’. Volatile terpenoids in the cephalic secretion of

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• the subject of the present paper. Results and Discussion Apart from a couple of known acyclic terpenoids (Figure 1), analysis by gas chromatography coupled with mass spectrometry (GC/MS) revealed the presence of an unknown minor component X in both sexes of Alloxysta victrix. Chemical ionization

• may turn out that the chiral center carrying the methyl group in the five-membered ring of iridoids may much more often show (R)-configuration than it is known today. Terpenoids 1–5 present in Alloxysta victrix and cis-fused bicyclic iridoids known from other insects (6–8). 70 eV EI-mass spectrum of

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• , alcohols, aldehydes, acyloins, nitrogen and oxygen heterocycles, aromatic compounds, and terpenoids. Carboxylic acids were dominating, and this class was composed of the branched isobutyric acid (49), isovaleric acid (50), and 2-methylbutyric acid (51) as the main compounds, with minor amounts of 5

• -5-methylfuran (76), decanal (77), 7-methyloctan-4-olide (78), nonan-4-olide (79), and the terpenoids linalool (80) and geranyl acetone (81). Besides the compounds mentioned above, several saturated FAMEs were present in the headspace extracts (Figure 4). All the identified FAMEs were divided into

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

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• complex systems such as fluorinated terpenoids, steroids and a range of heterocyclic systems, upon appropriate synthetic elaboration [7], and, consequently, there is much interest in the development of a synthetic methodology for the preparation of such useful fluorinated intermediates. It has been

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• -hydroxyvibsanin E; 3-O-methylfuranovibsanin A; natural products; terpenoids; vibsane; vibsanin E; Viburnum; Introduction Vibsane-type diterpenes occur exclusively in Viburnum species such as V. awabuki [1], V. odoratissimum [2] and V. suspensum [3], and can be regarded as quite rare natural products. Nine