Natural Product Reports (Nat Prod Rep)

Publications in this journal

• Article: Hot off the press.

  Robert A Hill, Andrew Sutherland
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  ABSTRACT: A personal selection of 33 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as asperterpenoid A, a metabolite of an endophytic Aspergillus species.
  Natural Product Reports 05/2013;
• Article: Glucuronides from metabolites to medicines: a survey of the in vivo generation, chemical synthesis and properties of glucuronides.

  Andrew V Stachulski, Xiaoli Meng
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  ABSTRACT: Covering: 1998 to 2011. Previous review: Nat. Prod. Rep., 1998, 15, 173-186The fourteen years that have passed since the previous review on this topic have seen a significant increase of interest in many aspects of glucuronide chemistry and biology. Glucuronides are the most important class of phase 2 xenobiotic metabolites and typically act in a detoxifying role. While this is generally true for O-alkyl and O-aryl glucuronides, a number of glucuronides are known to be pharmacologically active per se. Additionally the use of glucuronide prodrugs, notably to ameliorate the cytotoxicity of anticancer agents, has markedly increased. Whereas the previous review covered only the synthesis of O-glucuronides, we now include N-, S- and C-glucuronides also and discuss both synthetic and biological aspects. Synthetic methods for all classes of glucuronides are reviewed and updated, together with advances in the enzymatic synthesis of glucuronides and methods for their detection. Finally we discuss the biological reactivity of glucuronides where known, including the important morphine-6-glucuronide. A lively debate has continued for several years on whether O-acyl glucuronide metabolites of carboxylic acids are toxic, affecting both the safety assessment of well-used drugs and new drug development programmes. We summarise the current understanding, together with other known examples of interaction between glucuronides and macromolecules.
  Natural Product Reports 05/2013;
• Article: Muscarine, imidaozle, oxazole and thiazole alkaloids.

  Zhong Jin
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  ABSTRACT: Covering: July 2010 to June 2012. Previous review: Nat. Prod. Rep., 2011, 28, 1143-1191.Structurally diverse alkaloids containing five-membered heterocyclic subunits, such as imidazole, oxazole, thiazole, as well as their saturated congeners, are widely distributed in terrestrial and marine organisms and microorganisms. These naturally occurring secondary metabolites often exhibit extensive and pharmacologically important biological activities. The latest progress involving isolation, biological activities, chemical synthetic studies, and biosynthetic pathways of these natural products has been summarized in this review.
  Natural Product Reports 05/2013;
• Article: Marine natural products: synthetic aspects.

  Jonathan C Morris
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  ABSTRACT: Covering: January to December 2010. Previous review: Nat. Prod. Rep., 2011, 28, 269An overview of marine natural products synthesis during 2010 is provided. As with earlier installments in this series, the emphasis is on total syntheses of molecules of contemporary interest, new total syntheses, and syntheses that have resulted in structure confirmation or stereochemical assignments.
  Natural Product Reports 05/2013;
• Article: Hirsutellones and beyond: figuring out the biological and synthetic logics toward chemical complexity in fungal PKS-NRPS compounds.

  Xu-Wen Li, Alexandre Ear, Bastien Nay
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  ABSTRACT: Covering: up to early 2013Fungal polyketides and their hybrid non ribosomal peptide derivatives are characterized by often striking structural features and biological activities. Their diversity and their complexity arise from highly organized and programmable biosynthetic pathways and have been challenged by many synthetic chemists. This review will conceptually illustrate how complexity can be generated, starting from a general biosynthetic purpose (the fundaments of PKS-NRPS assembly lines) and finally showing how the particular class of hirsutellone compounds has emerged from such processes in relation to post-elongation and secondary tailoring events. Synthetic efforts to produce these natural products will be described with a special emphasis on complexity-generating strategies and steps. Thus, the biosynthetic and synthetic works will be analyzed in a continuous flow, focusing on both the logic of Nature and organic chemists.
  Natural Product Reports 05/2013;
• Article: From epoxomicin to carfilzomib: chemistry, biology, and medical outcomes.

  Kyung Bo Kim, Craig M Crews
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  ABSTRACT: Covering: 1992 to 2012The initial enthusiasm following the discovery of a pharmacologically active natural product is often fleeting due to the poor prospects for its ultimate clinical application. Despite this, the ever-changing landscape of modern biology has a constant need for molecular probes that can aid in our understanding of biological processes. After its initial discovery by Bristol-Myers Squibb as a microbial anti-tumor natural product, epoxomicin was deemed unfit for development due to its peptide structure and potentially labile epoxyketone pharmacophore. Despite its drawbacks, epoxomicin's pharmacophore was found to provide unprecedented selectivity for the proteasome. Epoxomicin also served as a scaffold for the generation of a synthetic tetrapeptide epoxyketone with improved activity, YU-101, which became the parent lead compound of carfilzomib (Kyprolis™), the recently approved therapeutic agent for multiple myeloma. In this era of rational drug design and high-throughput screening, the prospects for turning an active natural product into an approved therapy are often slim. However, by understanding the journey that began with the discovery of epoxomicin and ended with the successful use of carfilzomib in the clinic, we may find new insights into the keys for success in natural product-based drug discovery.
  Natural Product Reports 04/2013;
• Article: The antibody-drug conjugate: an enabling modality for natural product-based cancer therapeutics.

  Hans-Peter Gerber, Frank E Koehn, Robert T Abraham
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  ABSTRACT: Covering: up to the end of 2012The Antibody Drug Conjugate (ADC) is a therapeutic modality consisting of a monoclonal antibody attached to a cytotoxic, small-molecule payload. The antibody portion of the ADC serves as a transport vehicle that recognizes and binds to a protein antigen expressed in tumor tissues. The localized delivery and release of the payload within or near malignant cells allows for targeted delivery of a potent cytotoxic agent to diseased tissue, while reducing damage to antigen-negative, normal tissues. Recent years have witnessed an explosive increase in ADC-based therapies, due mainly to clinical reports of activity in both hematologic and epithelial cancers. Accompanying this upsurge in ADC development is a renewed interest in natural product cytotoxins, which are typically highly potent cell-killing agents, but suffer from poor drug-like properties and narrow safety margins when systemically administered as conventional chemotherapeutics. In this review, we discuss recent advances related to the construction of ADCs, the optimization of ADC safety and efficacy, and the increasingly pivotal roles of natural product payloads in the current and future landscape of ADC therapy.
  Natural Product Reports 03/2013;
• Article: Concepts and technologies for tracking bioactive compounds in natural product extracts: generation of libraries, and hyphenation of analytical processes with bioassays.

  Olivier Potterat, Matthias Hamburger
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  ABSTRACT: Covering: up to 2012Since the advent of high-throughput screening (HTS) in the early 1990s, a wealth of innovative technologies have been proposed and implemented for the effective localization and characterization of bioactive constituents in complex matrices. The latest developments in this field are reviewed under the perspective of their applicability to natural product-based drug discovery. The approaches discussed here include TLC-based bioautography, HPLC-based assays with on-line, at-line and off-line detection, as well as affinity-based methods, such as frontal affinity chromatography, pulsed ultrafiltration mass spectrometry, imprinted polymers, and affinity capillary electrophoresis. Selected practical examples are given to illustrate the strengths and limitations of these approaches in contemporary natural product lead discovery. In addition, compatibility issues of natural product extracts and HTS are addressed, and selected protocols for the generation of high quality libraries are presented.
  Natural Product Reports 03/2013;
• Article: 21st Century natural product research and drug development and traditional medicines.

  Linh T Ngo, Joseph I Okogun, William R Folk
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  ABSTRACT: Covering: 1987 to 2013Natural products and related structures are essential sources of new pharmaceuticals, because of the immense variety of functionally relevant secondary metabolites of microbial and plant species. Furthermore, the development of powerful analytical tools based upon genomics, proteomics, metabolomics, bioinformatics and other 21st century technologies are greatly expediting identification and characterization of these natural products. Here we discuss the synergistic and reciprocal benefits of linking these 'omics technologies with robust ethnobotanical and ethnomedical studies of traditional medicines, to provide critically needed improved medicines and treatments that are inexpensive, accessible, safe and reliable. However, careless application of modern technologies can challenge traditional knowledge and biodiversity that are the foundation of traditional medicines. To address such challenges while fulfilling the need for improved (and new) medicines, we encourage the development of Regional Centres of 'omics Technologies functionally linked with Regional Centres of Genetic Resources, especially in regions of the world where use of traditional medicines is prevalent and essential for health.
  Natural Product Reports 03/2013;
• Article: A global approach to analysis and interpretation of metabolic data for plant natural product discovery.

  Manhoi Hur, Alexis Ann Campbell, Marcia Almeida-de-Macedo, Ling Li, Nick Ransom, Adarsh Jose, Matt Crispin, Basil J Nikolau, Eve Syrkin Wurtele
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  ABSTRACT: Covering: up to 2013Discovering molecular components and their functionality is key to the development of hypotheses concerning the organization and regulation of metabolic networks. The iterative experimental testing of such hypotheses is the trajectory that can ultimately enable accurate computational modelling and prediction of metabolic outcomes. This information can be particularly important for understanding the biology of natural products, whose metabolism itself is often only poorly defined. Here, we describe factors that must be in place to optimize the use of metabolomics in predictive biology. A key to achieving this vision is a collection of accurate time-resolved and spatially defined metabolite abundance data and associated metadata. One formidable challenge associated with metabolite profiling is the complexity and analytical limits associated with comprehensively determining the metabolome of an organism. Further, for metabolomics data to be efficiently used by the research community, it must be curated in publicly available metabolomics databases. Such databases require clear, consistent formats, easy access to data and metadata, data download, and accessible computational tools to integrate genome system-scale datasets. Although transcriptomics and proteomics integrate the linear predictive power of the genome, the metabolome represents the nonlinear, final biochemical products of the genome, which results from the intricate system(s) that regulate genome expression. For example, the relationship of metabolomics data to the metabolic network is confounded by redundant connections between metabolites and gene-products. However, connections among metabolites are predictable through the rules of chemistry. Therefore, enhancing the ability to integrate the metabolome with anchor-points in the transcriptome and proteome will enhance the predictive power of genomics data. We detail a public database repository for metabolomics, tools and approaches for statistical analysis of metabolomics data, and methods for integrating these datasets with transcriptomic data to create hypotheses concerning specialized metabolisms that generate the diversity in natural product chemistry. We discuss the importance of close collaborations among biologists, chemists, computer scientists and statisticians throughout the development of such integrated metabolism-centric databases and software.
  Natural Product Reports 02/2013;
• Article: Perspectives on natural product epigenetic modulators in chemical biology and medicine.

  Fanny L Cherblanc, Robert W M Davidson, Paolo Di Fruscia, Nitipol Srimongkolpithak, Matthew J Fuchter
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  ABSTRACT: Covering: up to the end of 2012Epigenetic processes are complex regulatory transcriptional pathways that underpin fundamental physiology and are implicated in the aetiology of many diseases. Small molecule modulators of key epigenetic targets will be central in the study of these intricate networks as well as providing highly useful start points for drug discovery efforts. In this review we will give our perspective on the current status of natural product epigenetic modulators, highlighting the limitations, challenges and opportunities for currently identified molecules, as well as potential strategies for novel compound discovery moving forward.
  Natural Product Reports 02/2013;
• Article: Natural product isolation - how to get from biological material to pure compounds.

  Franz Bucar, Abraham Wube, Martin Schmid
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  ABSTRACT: Covering: 2008 to 2012Since the last comprehensive review by Otto Sticher on natural product isolation in NPR (O. Sticher, Nat. Prod. Rep., 2008, 25, 517), a plethora of new reports on isolation of secondary compounds from higher plants, marine organisms and microorganisms has been published. Although methods described earlier like the liquid-solid chromatographic techniques (VLC, FC, MPLC, HPLC) or partition chromatographic methods are still the major tools for isolating pure compounds, some developments like hydrophilic interaction chromatography (HILIC) have not been fully covered in previous reviews. Furthermore, examples of using different preparative solid-phase extraction (SPE) columns including molecular imprinting technology have been included. Special attention is given to chiral stationary phases in isolation of natural products. Methods for proper identification of plant material, problems of post-harvest changes in plant material, extraction methods including application of ionic liquids, de-replication procedures during natural product isolation are further issues to be discussed by the review. Selected work published between 2008 and mid-2012 is covered.
  Natural Product Reports 02/2013;
• Article: Marine Natural Products

  John W. Blunt, Brent R. Copp, Robert A. Keyzers, Murray H. G. Munro, Michèle R. Prinsep
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  ABSTRACT: This 2011 review of marine natural products describes 1152 new compounds and reports structural revisions and assignments of absolute configurations for previously described compounds. Included is an example of the development of genome mining for the discovery of new compounds from marine microbes leading to the finding of salinosporamide K from Salinispora pacifica.
  Natural Product Reports 02/2013; 30:237-323.
• Article: Bioinformatics challenges in de novo transcriptome assembly using short read sequences in the absence of a reference genome sequence.

  Elsa Góngora-Castillo, C Robin Buell
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  ABSTRACT: Plant natural product research can be facilitated through genome and transcriptome sequencing approaches that generate informative sequence and expression datasets that enable characterization of biochemical pathways of interest. As the overwhelming majority of plant-derived natural products are derived from species with little, if any, sequence and/or genomic resources, the ability to perform whole genome shotgun sequencing and assembly has been and will continue to be transformative as access to a genome sequence provides molecular resources and a context for discovery and characterization of biosynthetic pathways. Due to the reduced size and complexity of the transcriptome relative to the genome, transcriptome sequencing provides a rapid, inexpensive approach to access gene sequences, gene expression abundances, and gene expression patterns in any species, including those that lack a reference genome sequence. To date, successful applications of RNA sequencing in conjunction with de novo transcriptome assembly has enabled identification of new genes in an array of biochemical pathways in plants. While sequencing technologies are well developed, challenges remain in the handling and analysis of transcriptome sequences. In this Highlight article, we provide an overview of the bioinformatics challenges associated with transcriptome analyses using short read sequences and how to address these issues in plant species that lack a reference genome.
  Natural Product Reports 02/2013;
• Article: Open-chain steroidal glycosides, a diverse class of plant saponins.

  Victoria L Challinor, James J De Voss
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  ABSTRACT: Covering: up to September 2012Saponins are an important class of plant natural products that consist of a triterpenoid or steroidal skeleton that is glycosylated by varying numbers of sugar units attached at different positions. Steroidal saponins are usually divided into two broad structural classes, namely spirostanol and furostanol saponins. A third, previously unrecognized structural class of plant saponins, the open-chain steroidal saponins, is introduced in this review; these possess an acyclic sidechain in place of the heterocyclic ring/s present in spirostanols and furostanols. Open-chain steroidal saponins are numerous and structurally diverse, with over 150 unique representatives reported from terrestrial plants. Despite this, they have to date been largely overlooked in reviews of plant natural products. This review catalogs the structural diversity of open-chain steroidal saponins isolated from terrestrial plants and discusses aspects of their structure elucidation, biological activities, biosynthesis, and distribution in the plant kingdom. It is intended that this review will provide a point of reference for those working with open-chain steroidal saponins and result in their recognition and inclusion in future reviews of plant saponins.
  Natural Product Reports 02/2013;
• Article: Polycyclic xanthone natural products: structure, biological activity and chemical synthesis.

  Dana K Winter, David L Sloman, John A Porco Jr
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  ABSTRACT: Covering: 1972 to 2012Polycyclic xanthone natural products are a family of polyketides which are characterized by highly oxygenated, angular hexacyclic frameworks. In the last decade, this novel class of molecules has attracted noticeable attention from the synthetic and biological communities due to emerging reports of their potential use as antitumour agents. The aim of this article is to highlight the most recent developments of this subset of the xanthone family by detailing the innate challenges of the construction of this class of natural products, new synthetic approaches, and pharmacological data.
  Natural Product Reports 01/2013;
• Article: Using NMR to identify and characterize natural products.

  Rosemary C Breton, William F Reynolds
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  ABSTRACT: Covering: up to November 2012Over the past 28 years there have been several thousand publications describing the use of 2D NMR to identify and characterize natural products. During this time period, the amount of sample needed for this purpose has decreased from the 20-50 mg range to under 1 mg. This has been due to both improvements in NMR hardware and methodology. This review will focus on mainly methodology improvements, particularly in pulse sequences, acquisition and processing methods which are particularly relevant to natural product research, with lesser discussion of hardware improvements.
  Natural Product Reports 01/2013;
• Article: Hot off the press.

  Robert A Hill, Andrew Sutherland
  [show abstract] [hide abstract]
  ABSTRACT: A personal selection of 33 recent papers is presented covering various aspects of current developments in bioorganic chemistry and novel natural products such as breitfussin A from the Arctic hydrozoan Thuiaria breitfussi.
  Natural Product Reports 12/2012;
• Article: A genomic approach to the cryptic secondary metabolome of the anaerobic world.

  Anne-Catrin Letzel, Sacha J Pidot, Christian Hertweck
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  ABSTRACT: Covering: up to September 2012.A total of 211 complete and published genomes from anaerobic bacteria are analysed for the presence of secondary metabolite biosynthesis gene clusters, in particular those tentatively coding for polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS). We investigate the distribution of these gene clusters according to bacterial phylogeny and, if known, correlate these to the type of metabolic pathways they encode. The potential of anaerobes as secondary metabolite producers is highlighted.
  Natural Product Reports 12/2012;