Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines. Keywords

• [21], A. ochraceus [22], A. pseudodeflectus [17], A. carneus [23] and Aspergillus sp. strain IBWF002-96 [4][5] are biosynthetic sources of the drimane sesquiterpenoids. Drimane sesquiterpenoids, which are derived from a parent C15 pentamethyl-trans-decalin skeleton, are known to occur in plants

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• of years dating back well before biblical times [2][3]. Plants and resins served as source for perfumes after alcoholic extraction. These extracts were not only used as fragrances but also as medicine (aqua mirabilis), aphrodisiac and elixir of life (aquavitae). In 1882 'Fougere Royale' was created

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• [1][2][3]. Sesqui- and diterpenes are a diverse class of secondary metabolites derived predominantly from plants, marine invertebrates, fungi and some prokaryotes [4][5][6][7][8]. Properties of these natural products include antitumor, anti-oxidant, anti-inflammatory, antiviral, antimalarial

• . In fungi and plants, they can be both class I or class II TPSs and even mixed class I/II [21]. Class I TPSs harbor two distinct catalytic motifs, which are crucial for binding and correctly positioning the substrate for catalysis, the aspartate-rich motif (DDxxD) and the NSE/DTE motif, that bind to

• enzymes that is widely distributed among plants, fungi and bacteria. CotB2 has evolved to convert the acyclic, achiral substrate GGDP to the 5–8–5 ring motif of cyclooctat-9-en-7-ol that contains six chiral stereocenters. Hence, CotB2 has been fine tuned to perform a highly specific regio- and

Isolation and biosynthesis of an unsaturated fatty acid with unusual methylation pattern from a coral-associated bacterium Microbulbifer sp.

• Amit Raj Sharma,
• Enjuro Harunari,
• Tao Zhou,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2327–2332, doi:10.3762/bjoc.15.225

• -methylnonadecanoic acid (19:1 me(10)) are the major constituents of the cell wall of Mycobacterium phlei [20]. C9-Methylated glucosylceramides also possess a methyl-branching in the middle of the aliphatic carbon chain of the sphingosine part. C9-Methylated sphingolipids have not been found from plants and animals

Functionalization of 4-bromobenzo[c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

• Benedikt C. Melzer,
• Alois Plodek and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2304–2310, doi:10.3762/bjoc.15.222

• pyridoacridine alkaloids to be found in diverse marine sources (tunicates, sponges). Their chemistry, pharmacology and biosynthesis have been the subject of a couple of review articles [1][2][3][4]. Another source of polycyclic aromatic alkaloids are tropical plants, e.g., the Annonaceae family [5]. A very

Genome mining in Trichoderma viride J1-030: discovery and identification of novel sesquiterpene synthase and its products

• Xiang Sun,
• You-Sheng Cai,
• Yujie Yuan,
• Guangkai Bian,
• Ziling Ye,
• Zixin Deng and
• Tiangang Liu

Beilstein J. Org. Chem. 2019, 15, 2052–2058, doi:10.3762/bjoc.15.202

• . viride to date. Keywords: genome mining; metabolic engineering; natural products; sesquiterpene synthase; terpenes; Trichoderma viride J1-030; Introduction Terpenoids represent the most diverse group of natural products, with a wide distribution in microorganisms, plants, insects and various marine

Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• Withanolides are steroidal lactones widespread in Nightshade plants with often potent antiproliferative activities. Additionally, the structural diversity of this compound class holds much potential for the discovery of novel biological activity. Here, we report two newly characterised withanolides, named

• guidance for elucidating the enzymatic basis of androstane formation in plants in the future. Results and Discussion To isolate withanolides from P. peruviana, we used a purification strategy based on previous reports [17][18][19]. Nine weeks old whole P. peruviana plants (140 g) were extracted with H2O

•  3A) [22], their occurrence in plants is rare [23][24][25][26]. Only a single withanolide androstane has been fully characterised before, cinedione (8), isolated from Physalis cinerascens (Figure 3A) [23]. We propose the name androwithanolides for this withanolide subclass, which so far appears to be

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• biological effects. In plants, they are synthesized, among others, for pesticidal and antimicrobial effects. Two such compounds, archangelolide and trilobolide of the guaianolide type, are structurally similar to the well-known and clinically tested lactone thapsigargin. While trilobolide has already been

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• as components of a variety of plants and exhibit a wide range of biological properties including inhibition of glucosidases [102]. When the aziridine epoxide 162 was treated with acetic acid the aziridine ring cleavage was observed to give the epoxyaldehyde 178 (Scheme 45) [94]. Catalytic

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• depends on the precursors that these synthases can accommodate: geranyl diphosphate (monoterpenes, C10), farnesyl diphosphate (sesquiterpenes, C15) and geranylgeranyl diphosphate (diterpenes, C20). The biological function of terpenes is best studied for plants where they play important roles in

• played by terpenoids in plants [11]. However, although geosmin was discovered more than 50 years ago [14], its biological or ecological function still remains unclear. Streptomyces pactum KLBMP 5084 (the only species included in this study that does not carry geosmin synthases) is an endophytic plant

• evolution of terpenes synthases among Streptomyces species. It would be interesting in follow-up studies to assess the distribution and evolution of these genes among other bacteria, fungi, protists and plants. In addition, a deeper knowledge of the ecological function of terpenes in bacteria and in the

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• occur frequently in plants [11]. Whether the reduced selectivity of TSs both for substrates and for products can be attributed to imperfect catalysis, or if this function is even beneficial for the producing organism, remains elusive in most cases. Also the structural basis of promiscuous catalysis by

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• Pseudomonas cichorii causes varnish spots on lettuce. Varnish spots, also called midrib rot or bacterial rot [1][2][3][4], are dark brown and can induce necrotic lesions [1][2][3][4][5][6][7]. P. cichorii, isolated by us, infects a wide range of host plants, including monocot and dicot species (e.g

• ., Asteraceae, Solanaceae, Apiaceae, and Liliaceae; 54 species in 17 families) [5], but necrotic lesions most commonly occur in lettuce plants and seriously hurt lettuce production in the highland areas of Japan (e.g., Nagano and Iwate prefectures) in the summer season [5]. Effective ways of inhibiting the

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• giant neurons of the African giant snail appeared to be sensitive to various extents to all stereoisomers of 2 [21][22][23]. Hydroxyglutamic acids are widely spread in nature, especially in plants but they were also found in other species or as components of more complex molecules of interesting

• [(2S,4S)-3] was found in several plants, e.g., Phlox decussata [29] and other Phlox species [30], as well as in Linaria vulgaris [31]. It has also been discovered in mammalian cells as an intermediate in the degradation of hydroxyproline [32][33]. Its various amides have been identified in numerous

• plants [34][35][36][37][38][39] as well as components of complex molecules produced by different species [40][41][42]. 3,4-Dihydroxyglutamic acid (4) of unknown stereochemistry was identified as a constituent of seeds of Lepidum sativum and leaves of Rheum rhaponticum and later on in other species [43

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• )-quinolones (AQs) have been identified as natural products produced by higher plants of the Rutaceae family as well as by some microorganisms including Alteromonas, Burkholderia and Pseudomonas species [1][2][3][4][5][6][7][8][9]. Plant-derived AQs occur with alkyl chains of different lengths, branches and

• cytochromes in Mycobacteria than HQNO and therefore the methylation of HQNO can be seen as detoxification strategy [16]. Considering the natural occurrence of N- as well as O-methylated AQs in plants and the use of methylation of HQNO in Mycobacteria as detoxification reaction, we decided to investigate the

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• containing a carbohydrate-recognition domain similar to the CRD in ricin, a toxin of the poisonous plant Ricinus communis. R-type lectins have been detected in plants, animals, and bacteria. Plant R-type lectins often contain a separate subunit functioning as a toxin. Furthermore, ricin-type lectin domains

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• results. Keywords: computational calculation; per-O-methylation; quercetin; quercetin pentamethyl ether; reactivity; Introduction Flavonoids are distributed widely in plants, and exhibit various biological activities [1]. Polymethoxyflavones (PMFs) in particular have attracted much attention due to

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• to antineurodegenerative activities [2][3]. The majority of natural coumarins are secondary metabolites isolated from plants [5][6][7]. A commonly used taxonomy for these natural products (which has been extended to the non-natural analogues) is based on the coumarin structure (Figure 1) [4][8]. It

• ]. This consideration has, for example, led to the development of substituted angelicins rather than psoralens as potential anti-influenza drugs [16]. Seselin (4) is an example of an angular pyranocoumarin found in various plants, e.g., from the family of Rutaceae [17]. Among other bioactivities, the

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• also important in the interaction between different species, e.g., between ophiostomatoid fungi and conifer bark beetles that show different behavioural responses to fungal volatiles [9]. Fungal volatiles can also be of importance in the interaction between plants and fungi. In some cases, fungal

• germination and to cause necrotic lesions in the plant tissue. In other cases, fungal volatiles can have beneficial effects and may even be involved in the induction of systemic resistance in plants, as can be assumed for 6-pentyl-2H-pyran-2-one (5) that is produced by many fungi from the genus Trichoderma

• spectrometry in plants from the genus Asarum [45], but never from fungi before. However, it remains unclear how 45 was distinguished from 44 or other possible isomers in the earlier study. Conclusion Both investigated ascomycetes, Hypoxylon griseobrunneum and Hypoxylon macrocarpum, were found to emit complex

Studies towards the synthesis of hyperireflexolide A

• G. Hari Mangeswara Rao

Beilstein J. Org. Chem. 2018, 14, 2106–2111, doi:10.3762/bjoc.14.185

• hyperireflexolide A. Keywords: alkylation; allylation; cross metathesis; hyperireflexolide A; spiroterpene; Introduction Hyperireflexolide A (1) [1] is a spiroterpenoid, isolated from hypericum reflexum, plants of the genus hypericum (Figure 1). Hyperireflexolide A is widely used in folk medicine, displays

Assessing the possibilities of designing a unified multistep continuous flow synthesis platform

• Mrityunjay K. Sharma,
• Roopashri B. Acharya,
• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2018, 14, 1917–1936, doi:10.3762/bjoc.14.166

• plants [66]. The entire platform has separate tanks for storing the feed, product, solvent/buffer solution for extraction and waste collection. The feed storage tanks will be equipped with temperature control for preheating or precooling of any reagent before mixing. Moreover, the unified platform can be

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• association with animals or plants as pathogens or symbionts and exhibit a variety of catabolic and metabolic activities [1][7]. One hundred ten secondary metabolites have been reported from Burkholderia (data retrieved from the Dictionary of Natural Products, as of March 20, 2018). However, it is likely that

• )-one [17], 6 was identified as PSC-D or (E)-3-methyl-2-(non-2-en-1-yl)quinolin-4(1H)-one) [17], 7 was identified as pyrrolnitrin [18], and 8 was identified as BN-227 [19] (Figure 1). 4-Quinolone is a common core in synthetic antibactericides [20] and in bioactive metabolites produced by Rutaceae plants

• NBRC16015, Trichophyton rubrum NBRC5467, Candida albicans NBRC0197 (human opportunistic pathogen), R. oryzae NBRC4705, Glomerella cingulata NBRC5907 (pathogen of anthracnose), Ralstonia solanacearum SUPP1541 (pathogen of bacterial wilt of Solanaceous plants), Rhizobium radiobacter NBRC14554 (pathogen of

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• FPID/(4-MeOC6H4)3P will be described in the following part. Moreover, angiotensin I converting enzyme (ACE) inhibitory peptides, widely exist in plants and animals, can serve as potential antihypertensive pharmaceuticals [40][41][42]. The synthesis of two ACE inhibitory peptides proceeded smoothly in

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

• the penny bun (Boletus edulis) [7], but can also inhibit the growth of other fungi [8] which likely contributes to the induction of systemic resistance in plants by Trichoderma [9]. Fungal volatiles can also act as self-inhibitors of fungal germination [10] or as attractants for insects involved in

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• (2), another widespread fungal volatile, a plant growth promoting effect and an induction of systemic resistance in plants against fungi was observed [5]. The significant biological effects of these and other fungal volatiles recently resulted in a considerable interest of natural product chemists

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• coumarins arises from the fact that the coumarin skeleton is present in many natural products extracted from plants [1][2][3] and some of them show potent pharmacological activities, such as antidepressant [4], antimicrobial [5][6], antioxidants [7][8], anti-inflammatory [9][10], antinociceptive [11