Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• ketosynthases which catalyze Claisen-like condensation reactions, will be presented. Keywords: α-pyrones; biological activity; interconnecting ketosynthases; natural product; polyketides; Introduction α-Pyrones (1, also 2-pyrones) represent a moiety widespread in nature (Figure 1). The motif of a six-membered

• biosynthesis: The mechanisms of chain elongation resemble each other, and simple building blocks, e.g., acetyl-CoA and malonyl-CoA, are used to build up the molecule [74]. In general both, polyketides and fatty acids are assembled by repeating Claisen-condensations between an activated acyl-starter unit and

• system the final lactonization of the peptide-bound polyketide chain results in the pyrone ring. Type III systems synthesize a variety of aromatic polyketides. First discovered in plants, later PKS III systems have also been described in fungi and bacteria. BpsA (for Bacillus pyrone synthase) was

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

• ], but these aspects will not be discussed here. Instead, this review highlights recent biosynthetic studies using isotopes from major classes of natural products including polyketides, non-ribosomal peptides, hybrids thereof, isoprenoids and a few aromatic compounds that arise via the shikimate pathway

• may not precisely follow the IUPAC rules. Review Polyketides Polyketide synthases (PKS) are multidomain enzymes that catalyze the formation of natural products via reaction steps similar to fatty acid biosynthesis, in which C2-units are fused in Claisen condensations and modified in an iterative or

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

• metabolites. It is well known that these chemicals play specific roles for their host with respect to communication [1], sexual attraction [2] and defense [3]. Marine biodiversity has provided around three thousand new chemicals, the most predominant of which are associated with polyketides, peptides

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• photopyrone synthase (PpyS), which catalyzes the head-to-head condensation of two acyl moieties. Ketosynthases (KS) are the key enzymes involved in the biosynthesis of fatty acids and polyketides [8]. They are known to catalyze C–C bond formations via a Claisen condensation between acyl- and malonylthioesters

Selective methylation of kaempferol via benzylation and deacetylation of kaempferol acetates

• Qinggang Mei,
• Chun Wang,
• Weicheng Yuan and
• Guolin Zhang

Beilstein J. Org. Chem. 2015, 11, 288–293, doi:10.3762/bjoc.11.33

• controllable hydrolysis of multiple O-acetylated kaempferols. Eight mono-, di- and tri-O-methylated kaempferols were thus prepared with excellent yields. The reported protocol could be extended for the selective derivatization of polyhydroxylated natural products like polyketides or phenylpropanoids

A modular phosphate tether-mediated divergent strategy to complex polyols

• Paul R. Hanson,
• Susanthi Jayasinghe,
• Soma Maitra,
• Cornelius N. Ndi and
• Rambabu Chegondi

Beilstein J. Org. Chem. 2014, 10, 2332–2337, doi:10.3762/bjoc.10.242

• component in several potent biologically active polyketides [1][2][3][4]. This prevalence has led to the development of various synthetic methods for their construction [5]. In particular, divergent strategies are ideal for analog generation [6][7][8][9][10][11], which in turn, can enhance the quality of

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• absolute stereochemistry of the molecule [43][126][127][128][129][130][131][132]. Ambruticin S and jerangolid A (2010) The jerangolids [133][134] and the ambruticins [135][136][137] are part of two closely related families of linear polyketides with potent antifungal properties produced by a variety of

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

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

• ; 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

• sequencing and bioinformatics analysis of Streptomyces sp. LZ35. This finding suggests the potential of LZ35 to produce 3-HBA-containing polyketides [4]. A gdmAI (encoding the first geldanamycin PKS module) deletion strain LZ35ΔgdmAI was constructed [3][5], as the production of geldanamycins was much higher

• than other constituents in this strain. This mutant could provide a relatively “clean” background to facilitate the isolation of minor constituents. Here, we present the isolation and structural characterization of three new 3-HBA-containing polyketides, namely cuevaenes C–E (3–5), along with cuevaenes

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

• Frank Hahn,
• Nadine Kandziora,
• Steffen Friedrich and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 634–640, doi:10.3762/bjoc.10.55

• biosynthesis, we became interested in the formation of the (12Z,14E)-diene [7]. Z-configured double bonds are much rarer in polyketides than their E-configured counterparts, and their biosynthesis has not been thoroughly investigated yet [7][8][9]. Gene cluster analysis suggested that the double bond at

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

• 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

Tanzawaic acids I–L: Four new polyketides from Penicillium sp. IBWF104-06

• Louis P. Sandjo,
• Eckhard Thines,
• Till Opatz and
• Anja Schüffler

Beilstein J. Org. Chem. 2014, 10, 251–258, doi:10.3762/bjoc.10.20

• -University Mainz, Institute of Biotechnology and Drug Research, Duesbergweg 10–14, D-55128 Mainz, Germany 10.3762/bjoc.10.20 Abstract Four new polyketides have been identified in culture filtrates of the fungal strain Penicillium sp. IBWF104-06 isolated from a soil sample. They are structurally based on the

• same trans-decalinpentanoic acid skeleton as tanzawaic acids A–H. One of the new compounds was found to inhibit the conidial germination in the rice blast fungus Magnaporthe oryzae at concentrations of 25 μg/mL. Keywords: arohynapene; natural products; polyketides; structure elucidation; tanzawaic

• assignment, the structure of compound 4 was established as shown in Figure 5. The fourth member of the series was consequently named tanzawaic acid L (Figure 5). Along with compounds 1–4, four known polyketides were isolated and identified (Figure 5) as arohynapene A (5) [3], arohynapene B (6) [3], tanzawaic

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• ”, via D. Montesano 49, 80131 Napoli, Italy Department of Chemistry, University of Bristol, Cantocks Close, BS8 1TS Bristol, United Kingdom 10.3762/bjoc.9.331 Abstract In this paper the stereostructural investigation of two new oxygenated polyketides, plakilactones G and H, isolated from the marine

• between plakilactone G and plakilactone H allowed us to determine the absolute configuration in this two new oxygenated polyketides. Keywords: chemical shift calculations; DFT; NMR spectroscopy; quantitative NOE; stereochemical determination of flexible systems; Introduction In recent years the quantum

• conformationally flexible oxygenated polyketides, plakilactone G (1) and H (2) (Figure 1), isolated from a Fiji collection of the marine sponge Plakinastrella mamillaris. Results and Discussion Isolation and determination of the constitution of plakilactones G and H The chloroform extract from the Kupchan

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• different products and a broad range of structural diversity. Keywords: anthracyclines; carbohydrates; carbopalladation; catalysis; domino reaction; natural products; Introduction Anthracyclines are a widespread class of natural products which belong to the group of aromatic polyketides [1]. Most of them

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

• . This motif is found in its intact or modified form in indolocarbazoles, macrocyclic polyketides (cytochalasan alkaloids), the aporhoeadane alkaloids, meroterpenoids from Stachybotrys species and anthraquinone-type alkaloids. Concerning their biological activity, molecular structure and synthesis, we

• , dihydroxylation and a final deprotection step. Macrocyclic polyketides: The first cytochalasan alkaloids, cytochalasin A (51) and B (52), originally named phomins [39], were isolated in 1966 [39][40][41][42]. Since then, the number of natural products belonging to this family has increased to over 80. Some

• 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

New tridecapeptides of the theonellapeptolide family from the Indonesian sponge Theonella swinhoei

• Annamaria Sinisi,
• Barbara Calcinai,
• Carlo Cerrano,
• Henny A. Dien,
• Angela Zampella,
• Claudio D’Amore,
• Barbara Renga,
• Stefano Fiorucci and
• Orazio Taglialatela-Scafati

Beilstein J. Org. Chem. 2013, 9, 1643–1651, doi:10.3762/bjoc.9.188

• treasure troves of secondary metabolites. The chemical diversity of the isolated compounds ranges from unusual steroids (exemplified by the 4-methylene sterol theonellasterol [2][3] and truncated side-chain sulfated steroids [4]), to complex macrocyclic polyketides (as the well-known swinholide A, now a

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

• Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme

• the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeable N-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides of N-acetylcysteamine activated

• methylmalonate is studied and quantified, showing a surprisingly high and transferable activity of these polyketide synthase substrate analogues in vivo. Keywords: biosynthesis; coenzyme A; malonic acid; polyketide; polyketide synthase; Introduction Polyketides are ubiquitous natural products and find

Asymmetric organocatalytic decarboxylative Mannich reaction using β-keto acids: A new protocol for the synthesis of chiral β-amino ketones

• Chunhui Jiang,
• Fangrui Zhong and
• Yixin Lu

Beilstein J. Org. Chem. 2012, 8, 1279–1283, doi:10.3762/bjoc.8.144

• unsatisfactory and the enantioselectivities were modest [20]. In recent years, inspired by the enzymatic synthesis of polyketides and fatty acids in biological systems, the enantioselective decarboxylative reactions of malonic acid half thioesters (MAHTs) have received much attention. In this regard, various

Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

• Hiroki Oguri,
• Haruki Mizoguchi,
• Hideaki Oikawa,
• Aki Ishiyama,
• Masato Iwatsuki,
• Kazuhiko Otoguro and
• Satoshi Ōmura

Beilstein J. Org. Chem. 2012, 8, 930–940, doi:10.3762/bjoc.8.105

• collections of the elaborated cyclic scaffolds, nature has evolved biosynthetic machinery and often employs (1) modular assembly and (2) divergent cyclization [4]. As the simplest example of this structural diversification, the biosynthesis of aromatic polyketides is outlined in Figure 1a. Employing acetyl

• pharmacophore, based on the key features of scaffold, substructure and stereochemistry, which could be the proof of concept of our synthetic approach toward lead generation exploiting natural-product-inspired collections. (a) Biosynthetic outline of aromatic polyketides; (b) structure of indole alkaloids

Marilones A–C, phthalides from the sponge-derived fungus Stachylidium sp.

• Celso Almeida,
• Stefan Kehraus,
• Miguel Prudêncio and
• Gabriele M. König

Beilstein J. Org. Chem. 2011, 7, 1636–1642, doi:10.3762/bjoc.7.192

• B (2) showed selective antagonistic activity towards the serotonin receptor 5-HT2B with a Ki value of 7.7 µM. Keywords: marine fungi; natural products; phthalides; polyketides; Introduction Phthalides are a class of structurally very diverse secondary metabolites with more than 180 naturally

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• approaches towards libraries of new compounds or for rational biotransformation of existing leading compounds. This review gives an overview of the current trends in cyanobacterial natural-product research, with a special emphasis on the biosynthetic enzymes. Review Biosynthesis of peptides and polyketides

• ]. Parts of the domains (KR, DH, ER) are optionally used leading to a different reduction state of the keto groups of polyketides. There are also alternative PKS assembly lines cooperating with AT domains encoded in trans of the multienzymes [15], or PKS types comprising single modules that work

• cassette that is expected to be involved in β-branching of polyketides [52]. NRPS and PKS pathways in terrestrial cyanobacteria Nostopeptolide The nostopeptolide gene cluster was the first NRPS/PKS type gene cluster described for a terrestrial cyanobacterial strain, namely Nostoc sp. GSV 224 [53

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• Structural motifs such as 1,2-aminoalcohol, 1,2- and 1,3-diol are very prevalent features in natural products, especially polyketides. The structures of some of these, such as sorbistin A1 [1] or zwittermicin A [2], contain mostly aminopolyol moieties. Aminoalcohol and diol motifs are often constructed via

Phaeochromycins F–H, three new polyketide metabolites from Streptomyces sp. DSS-18

• Jian Li,
• Chun-Hua Lu,
• Bao-Bing Zhao,
• Zhong-Hui Zheng and
• Yue-Mao Shen

Beilstein J. Org. Chem. 2008, 4, No. 46, doi:10.3762/bjoc.4.46

• , Xiamen University, Xiamen, Fujian 361005, P. R. China School of Life Sciences, Xiamen University, No. 422 South Siming Road, Xiamen, Fujian 361005, China (address for correspondence); Phone: 86-592-2181722, Fax: 86-592-2181722 10.3762/bjoc.4.46 Abstract Three new polyketides, phaeochromycins F (1), G (2

• ), H (3), were obtained from the culture broth of marine actinomycete strain Streptomyces sp. DSS-18. Their structures were established on the basis of detailed spectroscopic analyses, including 1D-, 2D-NMR and HR-ESI MS techniques. Keywords: biological properties; isolation; polyketides; Streptomyces

• from marine derived actinomycetes, a strain of the genus Streptomyces was isolated from deep sediment collected from the west Pacific. Herein, we report the isolation and structure determination and biological properties of three new polyketides, namely phaeochromycins F (1), G (2) and H (3), from