Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• William A. Donaldson Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881, USA 10.3762/bjoc.16.166 Abstract The spliceostatins/thailanstatins are a family of linear peptides/polyketides that inhibit pre-mRNA splicing, and as such act as potent cytotoxic

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• and subjected to metabolite analysis, which resulted in the discovery of a novel cyclopeptide, pseudosporamide (1), along with three new oligomycin-class polyketides, pseudosporamicins A–C (2–4). The unusual structure of compound 1, featured by a biaryl-bond bridging across a tripeptide scaffold, N

• chain of the spiroacetal rings, which showed clear contrast to other oligomycin congeners and related polyketides with ring-truncation or expansion. The new macrolides 2–4 displayed potent antimicrobial activity against the Gram-positive bacterium Kocuria rhizohpila and the plant pathogenic fungus

• discovery of new natural products. Keywords: DFT-based calculation; oligomycin; peptide; polyketides; Pseudosporangium; rare actinomycetes; Introduction Microbial secondary metabolites have been used as therapeutic drugs [1], veterinary medicines [2], agrochemicals [3], food preservatives/colorings [4][5

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• ′-dimethylethane-1,2-diamine. Keywords: cross coupling; myxobacteria; natural product; ribolactone; Z-enamide; Introduction In the course of our program to provide synthetic access to biologically active natural products we targeted complex polyketides and depsipetides [1][2][3][4][5][6][7][8][9][10]. One

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• program from marine fungi, two new aromatic polyketides karimunones A (1) and B (2) and five known compounds (3–7) were isolated from sponge-associated Fusarium sp. KJMT.FP.4.3 which was collected from an Indonesian sponge Xestospongia sp. The structures of these compounds were determined by the analysis

• . collected in Karimunjawa National Park, Indonesia. This fungus produces a violet pigment in the mycelium and secretes pink to red pigments into the broth medium. Comprehensive chemospectroscopic analysis of the culture extract using HPLC/UV led to the isolation of two new aromatic polyketides, karimunones A

• database. HPLC/UV-guided purification of the secondary metabolites from this strain led to the isolation of two new polyketides, karimunones A (1) and B (2), together with five known compounds (3–7, Figure 1). Compound 1 was obtained as a red powder. TOF-HRESIMS analysis gave a deprotonated molecule [M − H

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

• -position (C2) of the acetate unit (Figure 3B) [13]. In contrast, methylation at the carbons derived from the carbonyl carbon of the acetate (C1) is quite unusual in fatty acids and polyketides. This unusual methylation pattern is reported for the polyketides of eukaryotic algae dinoflagellates. Some of the

• intermediate, from which deprotonation occurs at C9 to give an internal olefin (Scheme 1). In the case of 1, methylation at the C3 carbon is inconsistent with the regular methylation pattern that occurs in fatty acids synthesized by the FAS (fatty acid synthase) or polyketides from the PKS (polyketide synthase

• growth was observed. Structure of (2Z,4E)-3-methyl-2,4-decadienoic acid (1). COSY and key HMBC correlations for 1. Methylation pattern that can occur in fatty acids and polyketides. Incorporation of 13C-labeled precursors into 1. C-Methylation of alkenyl carbon in sphingolipid biosynthesis. Biosynthesis

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

• remarkable genetic potential to produce a large variety of secondary metabolites with different functions including antibiotics, antifungals, pigments or immunosuppressants [1][2][3]. These are compounds of diverse chemical nature such as polyketides, peptides, aminoglycosides or terpenoids [4][5

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• assembled by solution-phase synthesis and an open-chain analogue of the natural product was obtained. Keywords: jasplakinolide; marine natural products; Negishi coupling; polyketides; stereoselective synthesis; Introduction Our program on the synthesis of biologically active natural products with peptide

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• different compound classes including fatty acid derivatives and polyketides, aromatic compounds, terpenes, sulfur and nitrogen compounds, and halogenated compounds is produced by ascomycete fungi [1]. Possibly the most widespread volatile secondary metabolite from fungi is (R)-oct-1-en-3-ol (1, Scheme 1), a

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• predatory bacterium Herpetosiphon aurantiacus 114-95T as a test organism. This strain is capable to produce a variety of polyketides and nonribosomal peptides [13][14][15] and possesses pathways to supply specific building blocks for these natural products [16]. Furthermore, genomic analyses revealed that H

Sulfation and amidinohydrolysis in the biosynthesis of giant linear polyenes

• Hui Hong,
• Markiyan Samborskyy,
• Katsiaryna Usachova,
• Katharina Schnatz and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2017, 13, 2408–2415, doi:10.3762/bjoc.13.238

• mediomycin from S. blastmyceticus have been recently reported, encoding a separate extension module for all 27 cycles of chain extension [8]. These systems are attractive targets for knowledge-based engineering to produce novel antifungal compounds. A member of this class of polyketides, tetrafibricin from

• Streptomyces neyagawaensis (Scheme 1), is a potent inhibitor of the fibrinogen receptor, which suggests an even wider potential utility for such compounds [8][9]. We have previously shown that in the biosynthesis of giant macrocyclic antifungal polyketides (so-called marginolactones) compounds bearing a

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• an optimized C–C cross-coupling sequence with a Suzuki cross-coupling reaction as key step. Keywords: antibiotics; polyenes; polyketides; Stille reaction; Suzuki reaction; total synthesis; Introduction The elansolids are metabolites from the gliding bacterium Chitinophaga sancti (formerly

• elansolids B1 (2) and B2 (3) along with A3 (4) bearing the unusual p-quinone methide unit were isolated from the fermentation broth. All elansolids belong to the group of trans-polyketides type I [3][4][5][6]. For the first generation total synthesis of elansolid B1 (2) we utilized an endo-selective

• configured trienes present in polyketides [12][13][14][15]. Furthermore, we show how the intermediate p-methide quinone can be exploited to also prepare elansolid B2 (3). The improved synthesis allows more easily preparing analogues of the elansolids for further biological evaluation. Experimental General

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• polyketides (PK), which have frequently found their way into therapeutic applications. Rational engineering approaches have been performed during the last 25 years that seek to employ the “assembly-line synthetic concept” of megasynthases in order to deliver new bioactive compounds. Here, we highlight PKS

• ; protein design; Review Megasynthases are proteins in natural compound synthesis Microbial natural products represent a rich source of pharmaceutically relevant chemical entities. A major class is represented by polyketides (PK) exemplified by the antibiotics erythromycin and rifamycin, by the

From chemical metabolism to life: the origin of the genetic coding process

• Antoine Danchin

Beilstein J. Org. Chem. 2017, 13, 1119–1135, doi:10.3762/bjoc.13.111

• , essential for compartmentalisation [29]), a variety of (iso)peptides as in the synthesis of fatty acids today, non-ribosomal peptides and polyketides [30]. The involvement of thioesters in a primitive metabolism, predating the systematic input of phosphate has been documented by Segré and co-workers in a

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• . Keywords: anticancer agent; medicinal chemistry polyketides; synthetic methodology; total synthesis; Introduction The complex structures of polyketides continues to be a great challenge for synthetic chemists and has also been a key driver for the development of new methodologies [1][2][3][4][5][6][7][8

• ][9]. In many cases, total synthesis is of critical importance to enhance the supply of these often scarce metabolites and even complex polyketides have been prepared on an industrial scale [10][11]. These natural products are also valuable molecular probes for the discovery and evaluation of novel

• characteristic (Z,Z,E)-triene, a thiazole side chain and a characteristic sequence of eight methyl and hydroxy-bearing stereocenters. Synthetic chemistry is of key importance to enhance the supply of these scarce polyketides to fully evaluate the biological potential and develop them as potential drug candidates

Lipids: fatty acids and derivatives, polyketides and isoprenoids

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2017, 13, 793–794, doi:10.3762/bjoc.13.78

• Jeroen S. Dickschat Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Straße 1, D-53121 Bonn, Germany 10.3762/bjoc.13.78 Keywords: fatty acids; isoprenoids; polyketides; Lipids fulfill various functions in life as membrane

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• diverse secondary metabolites with pharmaceutically useful bioactivities. Importantly, members of the genus Streptomyces have been the main source of drug discovery programs due to their high capacity in secondary metabolism including polyketides, peptides, terpenoids, alkaloids, and amino acid

• /carbohydrate/nucleic acid derivatives [1][2]. One of the largest groups of bacterial secondary metabolites is polyketide from which a range of clinically used drugs have been developed. Polyketides still remain in the focus of drug development because of their structural complexity that can provide attractive

• structure and the antifungal potency, no further research has been reported for 1. There are two interesting aspects in the structure of butyrolactol A (1). First, among the polyketides, a tert-butyl group has been found exclusively in metabolites of marine cyanobacteria except for 1 [11][12][13][14

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• biosynthesis of reduced polyketides in bacteria by modular polyketide synthases (PKSs) proceeds with exquisite stereocontrol. As the stereochemistry is intimately linked to the strong bioactivity of these molecules, the origins of stereochemical control are of significant interest in attempts to create

• this approach to provide answers to fundamental biological questions. Keywords: chemical biology; polyketide synthases; reduced polyketides; stereocontrol; Introduction Reduced polyketides and their derivatives form the basis for a number of medicines in current clinical usage, notably anti

• economic importance of these compounds, there is significant interest in trying to generate new versions of polyketides for evaluation as drug leads. The significant bioactivity of these compounds derives from their complex structures (particularly when compared to the typical products of chemical

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• view, they can be divided into eight categories: fatty acids (and their derivatives: mono-, di- and triglycerides and phospholipids), acylglycerols, phosphoglycerides, sphingolipids, glycolipids and polyketides, which result from the condensation of ketoacyl groups, sterols (e.g., cholesterol) and

Evidence for an iterative module in chain elongation on the azalomycin polyketide synthase

• Hui Hong,
• Yuhui Sun,
• Yongjun Zhou,
• Emily Stephens,
• Markiyan Samborskyy and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2016, 12, 2164–2172, doi:10.3762/bjoc.12.206

• also neatly explains how the diversity of naturally-occurring complex polyketides is generated by a common biosynthetic mechanism, and provides clues to the evolution of these multienzymes through duplication, capture, deletion, and rearrangement of modules or individual domains [5]. It has both

• which it influences the structures of complex polyketides. We aimed to characterise three recently uncovered candidates for iterative operation within a modular PKS, based on sequencing of the structural genes showing fewer modules present in the gene cluster than required to furnish the observed

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• , polyketides, amino acids, fatty acids as well as acetogenins and terpenoids) are summarized in this review article. Putative structures of geraniol 1a (R = H) or 1b (R = H) (in 1924), their expected dihydroxylation products 2a or 2b and the true structure 3 as determined by Klein and Rojahn in 1965 [8

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

• studies. Keywords: biosynthesis; chemoenzymatic synthesis; enzymology; heterocycles; polyketides; Introduction Heterocycles Heterocycles are important structural elements, which are present in natural products from all classes and also in many biologically active synthetic compounds. They often

• [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

• ]. Polyketides Polyketide natural products are biosynthesised by polyketide synthases (PKSs) of the types I–III. Type I PKS are multimodular megaenzyme complexes that produce linear, reduced polyketides in an assembly line process that uses acyl carrier proteins (ACP), ketosynthase (KS) and acyl transferase (AT

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• predictably than molecules made from multi-domain megasynthases such as polyketides and non-ribosomal peptides. Cyclisation is a common post-translational modification in RiPP pathways and includes a multitude of transformations. These modifications are usually essential for the proper biological activity of

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

• metabolites can be found in various detailed reports [19][20][21][22][23]. The majority of these metabolites are either non-ribosomal peptides, e.g., cystobactamids 1–3 (Figure 1) [24], polyketides, e.g., aurafuron A (4) [25], or hybrids thereof, e.g., corallopyronin A (5, Figure 2) [26]. Interestingly, an

• from these polyketides, an array of nitrogen-containing metabolites was published recently by Jansen et al. [47]. They investigated three strains of N. pusilla isolated from coastal sediment samples – deemed halotolerant for this reason – for their secondary metabolite production. Two strains, Ari7 and

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• screening. The distinctive 12-membered macrolide scaffold in these natural products features an arabinose moiety (Figure 2), which is only rarely observed in bacterial polyketides. The main difference between gulmirecins A and B is the presence or absence of an isovalerate substituent. Comparison with the