Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• focus on their anticancer [29][30][31] and anti-HIV potential [30][32]. Several 4-thiazolidinone derivatives such as ralitoline (anticonvulsant), etozoline (antihypertensive), pioglitazone (hypoglycemic) and thiazolidomycin (activity against streptomyces species) are already in the market [33]. Beyond

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

• Ulrike Groenhagen Michael Maczka Jeroen S. Dickschat Stefan Schulz Institut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany 10.3762/bjoc.10.146 Abstract Streptomyces sp. FORM5 is a bacterium that is known to produce the antibiotic streptazolin

• [2] such as methyl pyrrole-2-carboxylate, emitted by Stackebrandtia nassauensis, or 2-acetylpyrrole from Saccharopolyspora erythraea, volatile alkaloids are rarely produced by actinomycetes. We became interested in the strain Streptomyces sp. FORM5 to elucidate whether volatile formation is linked to

• aqueous phase. In our study the volatile bouquet of the actinomycete Streptomyces sp. FORM5 was investigated and several new 2-alkylated pyridines were identified using the closed-loop stripping analysis (CLSA) [7] headspace technique followed by GC–MS analysis and synthesis of the target compounds for

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

• only allylic alcohols. Immediate heme surroundings shown for the nearest relative of CYP154E1 with available crystal structure (CYP154A1, from Streptomyces coelicolor, PDB entry 1ODO). The residue in position 5 after the conserved ExxR motif (V286 in CYP154E1, green) reaches close to the heme centre

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• /bjoc.10.121 Abstract The heronapyrroles A–C have first been isolated from a marine-derived Streptomyces sp. (CMB-0423) in 2010. Structurally, these natural products feature an unusual nitropyrrole system to which a partially oxidized farnesyl chain is attached. The varying degree of oxidation of the

• : biomimetic synthesis; biosynthesis; heronapyrroles; microbial biodiscovery; natural products; nitropyrroloterpenes; Introduction Heronapyrroles A–C (Figure 1) were first reported in 2010 by Capon et al. from a marine-derived Streptomyces sp. (CMB-M0423) obtained from a shallow water sand sample collected

• initiate a cyclization cascade [1][3][8] that would provide the bis-tetrahydrofuran heronapyrrole C (Scheme 1), via a mechanism that closely resembles polyether antibiotic biosynthesis [12][13][14][15][16][17]. This biosynthetic hypothesis raises the possibility that Streptomyces sp. (CMB-M0423) may

Cuevaenes C–E: Three new triene carboxylic derivatives from Streptomyces sp. LZ35ΔgdmAI

• Jing-Jing Deng,
• Chun-Hua Lu,
• Yao-Yao Li,
• Shan-Ren Li and
• Yue-Mao Shen

Beilstein J. Org. Chem. 2014, 10, 858–862, doi:10.3762/bjoc.10.82

• isomers – cuevaenes A (1) and C (3) as well as cuevaenes D (4) and E (5) – and cuevaene B (2) were isolated from gdmAI-disrupted Streptomyces sp. LZ35. The constitution of cuevaene C (3) was found to be identical to cuevaene A (1) by means of NMR spectroscopy and high resolution mass spectrometry. However

• ; geometrical isomer; natural products; Streptomyces sp. LZ35; Introduction Cuevaenes are polyketides containing 3-hydroxybenzoic acid (3-HBA). Only 4 naturally occurring cuevaenes are described. Cuevaenes A and B were isolated from Streptomyces sp. HKI 0180 fifteen years ago and display moderate antibacterial

• activity against Gram-positive bacteria [1]. JBIR-23 and JBIR-24, novel anti-malignant pleural mesothelioma (MPM) agents, were isolated from Streptomyces sp. AK-AB27 six years ago [2]. All of these natural products have a tricyclic core and a polyene side chain with an enolmethyl ether inside. This type of

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• steps in monensin biosynthesis, namely hydroxylation catalysed by the P450 monooxygenase MonD and O-methylation catalysed by the methyl-transferase MonE. The corresponding genes were deleted in-frame in a monensin-overproducing strain of Streptomyces cinnamonensis. The mutants produced the expected

• tailoring step as well as polyether formation. Keywords: antibiotics; biosynthesis; natural products; polyketides; Streptomyces; synthetic biology; Introduction Monensin A (1) from Streptomyces cinnamonensis is one of the most prominent and best-studied of the polyether class of complex polyketides, an

• (5) and (d) the overlay of 5 (blue) with sodium monensin (1) (green). The proposed pathway for monensin biosynthesis in Streptomyces cinnamonensis. The polyketide synthase (PKS) initially produces an enzyme-bound triene, which is transferred to a discrete acylcarrier protein (ACPX) to give 2. After

[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

• Streptomyces griseus. This compound represents the first completely deuterated terpene obtained by fermentation. Despite a few previous reports in the literature the operability of this approach to fully deuterated compounds is still surprising, because the strong kinetic isotope effect of deuterium is known

• to slow down all metabolic processes in living organisms. Potential applications of completely labelled compounds from natural sources in structure elucidation, biosynthetic or pharmacokinetic investigations are discussed. Keywords: biosynthesis; deuterium; labelling; natural products; Streptomyces

• ; terpenes; Introduction The actinomycete Streptomyces griseus is a producer of three terpenes, 2-methylisoborneol (2-MIB, 1), (+)-caryolan-1-ol (2), and (+)-1-epi-cubenol (3, Figure 1). The biosynthesis of 2 and 3 requires the action of well characterized terpene cyclases [1][2], while the biosynthesis of

Halogenated volatiles from the fungus Geniculosporium and the actinomycete Streptomyces chartreusis

• Tao Wang,
• Patrick Rabe,
• Christian A. Citron and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 2767–2777, doi:10.3762/bjoc.9.311

• brominated or even iodinated volatiles are even more rare. Surprisingly, headspace extracts from Streptomyces chartreusis contained methyl 2-iodobenzoate, a new natural product that adds to the small family of iodinated natural products. Keywords: constitutional isomerism; GC-MS; natural products

• haloperoxidases [19]. Here we report on the identification of two chlorinated volatile compounds from the fungus Geniculosporium and a iodinated volatile from Streptomyces chartreusis. Results and Discussion Chlorinated volatiles from Geniculosporium The volatiles emitted by agar plate cultures of the fungus

• ) [25] or the trichlorinated phenols 20–22 (Figure 5) [26]. The biological function of 4b and 10b in Geniculosporium is unknown, but the antibiotic activity of the related compound drosophilin A towards bacteria is well known [27]. A iodinated volatile from Streptomyces chartreusis During the course of

The regulation and biosynthesis of antimycins

• Ryan F. Seipke and
• Matthew I. Hutchings

Beilstein J. Org. Chem. 2013, 9, 2556–2563, doi:10.3762/bjoc.9.290

• biosynthetic pathway. Keywords: antimycins; gene regulation; genome mining; natural products; Streptomyces; Review It is estimated that around 60% of all known antibiotics are derived from secondary metabolites made by filamentous actinomycete bacteria, most notably Streptomyces species [1]. Streptomyces

• neighbouring microbes [3]. In recent years genome sequencing has revealed that each Streptomyces species encodes many more specialised metabolites than it makes in laboratory culture, leading to new efforts to activate these so-called “silent pathways.” The number of known antibiotics made by Streptomyces

• host. This approach has already been used to identify novel chemical scaffolds of antibiotics produced by well-studied Streptomyces species [4][5][6] and to identify the biosynthetic gene clusters for commercially important antibiotics [7][8][9][10][11]. The latter allows cloning, optimisation and

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

• have a huge potential for the development of new chemistry. Review Indolocarbazoles. Staurosporine (26) was the first member of the indolocarbazole alkaloid family to be discovered by Ōmura from Streptomyces staurosporeus at the Kitasato Institute in 1977 [16]. Over the past 35 years, more than 60

• Zakarian reported another approach to the fully elaborated isoindolinone core of 204 [154]. Chlorizidine A (208) (Scheme 27), a cytotoxic metabolite from a marine Streptomyces species shows an unprecedented 5H-pyrrolo[2,1-a]isoindolinone ring system, which is connected to a dichlorinated pyrrolizine [155

• basis of the structural similarity between 208 and marinopyrrole A, another secondary metabolite derived from a marine Streptomyces species [156]. The common biosynthetic precursor 206 stems from a mixed nonribosomal peptide synthetase (NRPS)/polyketide synthase (PKS) pathway. The amino acid proline is

An approach towards azafuranomycin analogs by gold-catalyzed cycloisomerization of allenes: synthesis of (αS,2R)-(2,5-dihydro-1H-pyrrol-2-yl)glycine

• Jörg Erdsack and
• Norbert Krause

Beilstein J. Org. Chem. 2013, 9, 1936–1942, doi:10.3762/bjoc.9.229

• ; amino acids; cuprates; furanomycin; gold catalysis; Introduction In 1967, Katagiri et al. reported the isolation of a novel antibiotic from the culture broth of the fungus Streptomyces threomyceticus [1]. The compound acts as a competitive antagonist for isoleucine in vitro and hampers the growth of

Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

• Dinesh Simkhada,
• Huitu Zhang,
• Shogo Mori,
• Howard Williams and
• Coran M. H. Watanabe

Beilstein J. Org. Chem. 2013, 9, 1768–1773, doi:10.3762/bjoc.9.205

• ; Streptomyces; Findings It has become increasingly apparent that microbial diversity in nature far exceeds that reflected in laboratory strain collections. The advent of microbial genomics and the availability of published genome sequences suggest, that as much as 90% of the chemical potential of these

• precursors of the orphan pathway are fed to the organism and used to screen extracts of the fermentation broth, to identify metabolites containing the labeled precursors [9][10]. Here, we have carried out a functional knockout of aziA2 within the azinomycin gene cluster of Streptomyces sahachiroi [11][12

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• of the fermentation extracts, the incorporation was to be quantified in an erythromycin-producing strain of Saccharopolyspora erythraea (NRRL B-24071) and a rapamycin-producing strain of Streptomyces hygroscopicus (NRRL 5491) through the corresponding shift in the isotope ratio. For feeding

• ) and the supernatant was dried in vacuo. The residue was redissolved in 1 mL methanol, filtered and used for analysis. Rapamycin: Streptomyces hygroscopicus NRRL 5491 was grown on SY agar [46] at 28 °C. Fermentation was carried out in 50 mL Erlenmeyer flasks containing a steel spring. A 0.5 cm × 0.5 cm

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• . Results and Discussion Design and synthesis of biotinylated purine scaffold Hsp90 probes Geldanamycin (GM) is a benzoquinone ansamycin first isolated from a fermentation broth of Streptomyces hygroscopicus [15] and was the first reported Hsp90 inhibitor [16]. It has played a paramount role as a probe

Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• , Streptomyces bacteria, Sinacalia tangutica plants, and Eurypon sponges (Figure 1) [3][4][5][6]. The carbon skeleton of 1 is unusual, not only because it contains concatenated 4-, 6-, and 7-membered rings, but also in that it bears a bridgehead double bond. As noted in the original isolation report [2], this

A new approach toward the total synthesis of (+)-batzellaside B

• Jolanta Wierzejska,
• Shin-ichi Motogoe,
• Yuto Makino,
• Tetsuya Sengoku,
• Masaki Takahashi and
• Hidemi Yoda

Beilstein J. Org. Chem. 2012, 8, 1831–1838, doi:10.3762/bjoc.8.210

• was isolated from Streptomyces roseochromogenes R-468 and S. lavendulae SF-425 in the 1960s [5], this class of compounds has attracted a great deal of interest in the medical community due to their promising pharmaceutical potential as antidiabetic [6], antitumor [7] and antiviral [8] agents

Synthetic studies towards bottromycin

• Stefanie Ackermann,
• Hans-Georg Lerchen,
• Dieter Häbich,
• Angelika Ullrich and
• Uli Kazmaier

Beilstein J. Org. Chem. 2012, 8, 1652–1656, doi:10.3762/bjoc.8.189

• fermentation broth of Streptomyces bottropensis, called bottromycin [4][5][6]. This antibiotic inhibits the growth of a wide range of microorganisms by interfering with their protein biosynthesis [7][8][9][10][11][12]. In 1965 Nakamura et al. isolated closely related antibiotics from the strain Streptomyces No

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• ansamitocin producer [13][14][15][16][17], and Streptomyces hygroscopicus, the geldanamycin producer [18][19]. These engineered strains are unable to biosynthesize 3-amino-5-hydroxybenzoic acid (1) [20], the common starter unit for both polyketide synthases (PKS) (Scheme 1). These assembly-line-type

An intramolecular inverse electron demand Diels–Alder approach to annulated α-carbolines

• Zhiyuan Ma,
• Feng Ni,
• Grace H. C. Woo,
• Sie-Mun Lo,
• Philip M. Roveto,
• Scott E. Schaus and
• John K. Snyder

Beilstein J. Org. Chem. 2012, 8, 829–840, doi:10.3762/bjoc.8.93

• grossularia (Stylidae) [1][2], and desmethylgrossularine-1 from tunicate Polycarpa aurata [3]. Other natural α-carbolines include mescengricin (3), an inhibitor of L-glutamate excitotoxicity in neutrons, isolated from Streptomyces griseoflavus [4], and cryptotackieine (4) [5], also known as neocryptolepine [6

Identification and isolation of insecticidal oxazoles from Pseudomonas spp.

• Florian Grundmann,
• Veronika Dill,
• Andrea Dowling,
• Aunchalee Thanwisai,
• Edna Bode,
• Narisara Chantratita,
• Richard ffrench-Constant and
• Helge B. Bode

Beilstein J. Org. Chem. 2012, 8, 749–752, doi:10.3762/bjoc.8.85

• identified in this article, are not only prevalent in Pseudomonas but also in other bacteria such as Streptomyces [20] or Streptoverticillium [8][10], suggesting a biological relevance also in these bacteria. However, as concluded from the observed activity against insect cells, they could significantly add

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• , 72076 Tübingen, Germany 10.3762/bjoc.8.57 Abstract The biosynthetic gene cluster for endophenazines, i.e., prenylated phenazines from Streptomyces anulatus 9663, was heterologously expressed in several engineered host strains derived from Streptomyces coelicolor M145. The highest production levels were

• the first investigation of the regulatory genes of phenazine biosynthesis in Streptomyces. Keywords: phenazine; gene cluster; gene inactivation; Introduction Phenazine natural products have important biological activities comprising antibacterial, antifungal, antitumor, antimalarial, antioxidant and

• phenazines are secondary metabolites, produced mainly by different species of the proteobacterium Pseudomonas and of the actinobacterium Streptomyces. While Pseudomonas strains produce phenazine derivatives with relatively simple structures, more complex phenazines are produced by Streptomyces strains [1

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• ][23][24]. So far, five bacterial proline hydroxylases have been cloned and overexpressed in E. coli: A trans-4-proline hydroxylase (trans-P4H) from Dactylosporangium sp. [25] two cis-3-proline hydroxylase isoenzymes from Streptomyces sp. strain TH1 (cis-P3H_I and cis-P3H_II) [26][27] and two cis-4

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• , nojirimycin (NJ, trivial name for 5-amino-5-deoxy-D-glucopyranose) (59), the first alkaloid discovered that mimicks a sugar (originally isolated from Streptomyces filtrate but also found in other bacterial cultures and plant sources), is a potent glycosidase inhibitor. In aqueous solution nojirimycin exists

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• manumycin C (12) isolated from Streptomyces parvulus [13]. Different groups have investigated the synthesis of gymnastatins 10a–c [14][15][16], compounds 11 [17] and 12 [18]. In most cases, the lateral acid chain was prepared starting from (R)-2-methyloctanal by iterative Wittig reactions to build the

Stereoselective synthesis of four possible isomers of streptopyrrolidine

• Debendra K. Mohapatra,
• Barla Thirupathi,
• Pragna P. Das and
• Jhillu S. Yadav

Beilstein J. Org. Chem. 2011, 7, 34–39, doi:10.3762/bjoc.7.6

• Streptomyces sp. found in deep sea sediments [12]. The system is present in many biologically active compounds [13][14][15][16][17][18][19][20][21] and it could act as a versatile intermediate for the synthesis of a wide range of γ-amino acids as well as pyrrolidines [22][23]. The interesting chemical