Download or read book Synthetic Studies Towards Polyketide Derived Biologically Active Natural Products written by Amanda Heapy and published by . This book was released on 2009 with total page 227 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Synthetic Studies Applied to Polyketide Natural Products written by Alexander Mandel and published by . This book was released on 2008 with total page 318 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polyketide natural products are valuable components of the modern pharmacopea. These secondary metabolites have a diverse range of structures and activities. Studies of their biosynthesis and activity will help to provide access to better medicinal compounds. To this end, directly probing these mechanisms with derivatives of natural products is an important goal. Synthetic organic chemistry allows production of a greater variety of compounds than can be accessed by manipulation of isolated natural products. In some cases, these bioactive molecules are only obtainable in small quantities or at great expense. Herein, a modular synthesis of the Coenzyme A (10) precursors pantethine (35) and phosphopantetheine (14) is described. CoA is a cofactor that interacts with an estimated 4% of all enzymes known in nature, and it is central to the biosynthesis of polyketide antibiotics. Using d-pantolactone (50) to provide the key units, 53 and 63, pantetheine, phosphopantetheine, and derivatives were assembled through peptide couplings. Next, synthetic methods were applied toward the total synthesis of two related macrolide antibiotics, pladienolide B (70b) and FD-895 (71), in an attempt to elucidate their stereochemistries and to get a supply of each molecule for studies into the their stereochemistries and to get a supply of each molecule for studies into the molecule relies on a Stille coupling to connect the sidechain (133) to the 12-membered macrocyclic core (111), and an esterification / ring-closing metathesis sequence to furnish the ring from compounds 115 and 114. The sidechain of pladienolide B was completed and involved in model studies to demonstrate the overall retrosynthetic background. The core structure was proposed to arise from the chiral pool, but the strategy to combine the two units with the necessary stereochemistry met with failure under many different conditions. Due to complications in obtaining an authentic sample of pladienolide B (70b), and subsequent outside publication of a total synthesis incorporating many aspects of the work contained herein, FD-895 (71) was chosen as an alternative target. The same retrosynthetic breakdown was applied to FD-895.

Download or read book Comprehensive Natural Products III written by and published by Elsevier. This book was released on 2020-07-22 with total page 4266 pages. Available in PDF, EPUB and Kindle. Book excerpt: Comprehensive Natural Products III, Third Edition, Seven Volume Set updates and complements the previous two editions, including recent advances in cofactor chemistry, structural diversity of natural products and secondary metabolites, enzymes and enzyme mechanisms and new bioinformatics tools. Natural products research is a dynamic discipline at the intersection of chemistry and biology concerned with isolation, identification, structure elucidation, and chemical characteristics of naturally occurring compounds such as pheromones, carbohydrates, nucleic acids and enzymes. This book reviews the accumulated efforts of chemical and biological research to understand living organisms and their distinctive effects on health and medicine and to stimulate new ideas among the established natural products community. Provides readers with an in-depth review of current natural products research and a critical insight into the future direction of the field Bridges the gap in knowledge by covering developments in the field since the second edition published in 2010 Split into 7 sections on key topics to allow students, researchers and professionals to find relevant information quickly and easily Ensures that the knowledge within is easily understood by and applicable to a large audience

Download or read book Synthetic Studies on Polyketide Derived Natural Products and Intermediates written by Sarah Elaine Newberry and published by . This book was released on 2009 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Synthetic Studies Towards Aromatic Polyketide Derived Natural Products written by Peter Jaein Choi and published by . This book was released on 2011 with total page 287 pages. Available in PDF, EPUB and Kindle. Book excerpt: "The first part of this thesis describes the successful synthesis of a series of 6,6- bisbenzannulated spiroketal analogues of the rubromycin family. The synthesis of spiroketals 183a-183e and spiroaminal 237 were successfully executed using a novel microwave-assisted DIHMA approach. Coupling of an aryl acetylene and an aryl aldehyde via acetylide anion addition resulted in the formation of an alkynol which was followed by oxidation to the desired ynone. Spirocyclisation using the DIHMA protocol afforded the desired bisbenzannulated spiroketals 183a-183e and spiroaminal 237 in good yields. Hydroxy-substituted 6,6- bisbenzannulated spiroketal 182 was successfully furnished by the reduction of ketosubstituted 6,6-bisbenzannulated spiroketal 183a with sodium borohydride. The second part of this research presents synthetic attempts to access the chiral 3-substituted phthalide containing natural products; aigialospirol (256) and herbaric acid (255). The synthesis of chiral vinylphthalide 406 proved challenging and was overcome by the use of a microwave-assisted chemoenzymatic resolution to install the C3 stereocenter of phthalide 406. Despite various attempts to functionalise vinylphthalide 406 towards the synthesis of aigialospirol, results were unsuccessful. With chiral vinylphthalide 406 in hand, the first synthesis and the structural assignment of ( -- )-herbaric acid (255) was accomplished. This was achieved via heteroatom-directed Wacker oxidation on vinylphthalide 406 to form aldehyde 460. Aldehyde 460 underwent smooth oxidation with Oxone® affording acid 488 which underwent facile methyl ester formation to facilitate purification, thus delivering enantioenriched lactone ester 489. Smooth demethylation with concomitant ester hydrolysis was effected by boron tribromide to give ( -- )-herbaric acid (255). The realisation of this entirely regioselective anti-Markovnikov addition of water during the Wacker oxidation provides a mild alternative to hydroboration/oxidation protocols that are traditionally used for terminal alkenes"--Abstract.

Download or read book Synthesis of Polyketide derived Natural Products from Carbohydrates written by N.Y. Sin and published by . This book was released on 1996 with total page 235 pages. Available in PDF, EPUB and Kindle. Book excerpt: Considerable effort has focused on the development of synthetic methodology to effectively construct the unique structural subunits found within biologically active, polyketide-derived natural products. One successful approach begins with carbohydrates as chiral building blocks from which the complex structure and stereochemistry of polyketide-related intermediates can be elaborated. This dissertation describes the development of a synthetic strategy which utilizes carbohydrates in combination with the (2,3) -Wittig rearrangement for the synthesis of polyketide-derived natural products.

Download or read book Synthetic and Biosynthetic Studies on Polyketide Derived Natural Products written by and published by . This book was released on 2012 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Bioactive Compounds from Natural Sources Second Edition written by Corrado Tringali and published by CRC Press. This book was released on 2011-09-27 with total page 650 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first edition of Bioactive Compounds from Natural Sources was published in a period of renewed attention to biologically active compounds of natural origin. This trend has continued and intensified—natural products are again under the spotlight, in particular for their possible pharmacological applications. Largely focusing on natural products as lead compounds in drug discovery, Bioactive Compounds from Natural Sources, Second Edition: Natural Products as Lead Compounds in Drug Discovery is actually a completely new volume containing surveys of selected recent advances in an interdisciplinary area covering chemistry of natural products, medicinal chemistry, biochemistry, and other related topics. Written by some of the most reputed scientists in the field, this second edition includes new chapters from authors who contributed to the first edition as well as many chapters compiled by new authors. Introducing the reader to strategies and methods in the search for bioactive natural products, this book covers topics including: Natural sources of bioactive compounds such as aquatic cyanobacteria, filamentous fungi, and tropical plants, The tremendous potentiality of metabolic engineering of natural products biosynthesis The contribution of emerging or developing technologies to the study of bioactive natural compounds, namely computational methods and circular dichroism The potential of natural or natural-derived compounds for specific therapeutic applications: treatment of viral diseases, regulation of hypoxia-inducible factor, antimalarials, modulation of angiogenesis, and antitumor and wound-healing activity Selected examples of natural product families and related synthetic analogues, namely polyphenols and campthotecins Compiled for researchers and Ph.D. students working in interdisciplinary fields, this book will also be appreciated by readers without a background in chemistry interested in bioactive natural products, their biological and pharmacological properties, and their possible use as chemopreventive or chemotherapeutic agents. Conversely, the biological and pharmacological data and methods are accessible by chemists.

Download or read book Plant derived Natural Products written by Anne E. Osbourn and published by Springer Science & Business Media. This book was released on 2009-07-07 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plants produce a huge array of natural products (secondary metabolites). These compounds have important ecological functions, providing protection against attack by herbivores and microbes and serving as attractants for pollinators and seed-dispersing agents. They may also contribute to competition and invasiveness by suppressing the growth of neighboring plant species (a phenomenon known as allelopathy). Humans exploit natural products as sources of drugs, flavoring agents, fragrances and for a wide range of other applications. Rapid progress has been made in recent years in understanding natural product synthesis, regulation and function and the evolution of metabolic diversity. It is timely to bring this information together with contemporary advances in chemistry, plant biology, ecology, agronomy and human health to provide a comprehensive guide to plant-derived natural products. Plant-derived natural products: synthesis, function and application provides an informative and accessible overview of the different facets of the field, ranging from an introduction to the different classes of natural products through developments in natural product chemistry and biology to ecological interactions and the significance of plant-derived natural products for humans. In the final section of the book a series of chapters on new trends covers metabolic engineering, genome-wide approaches, the metabolic consequences of genetic modification, developments in traditional medicines and nutraceuticals, natural products as leads for drug discovery and novel non-food crops.

Download or read book Chemoenzymatic Synthesis of Polyketide Natural Products written by Taylor P. A. Hari and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Polyketide secondary metabolites constitute a structurally-diverse and clinically-important family of natural products. The wide range of biological activities represented by these substrates have contributed to therapeutic agents with annual sales exceeding $20B USD. Large multi-domain proteins called polyketide synthases (PKSs) use simple building blocks to generate highly-oxygenated and stereochemically-rich frameworks with astonishing selectivity. These substrates often feature rigidifying biases imposed by macrocyclic lactones and substituted heterocycles, which can impact their bioactive conformation. The work of this dissertation combines synthetic chemistry and biochemistry to investigate chemoenzymatic production of macrocyclic polyketide natural products. Research focused on validating a transannular oxa-conjugate addition strategy to assembly 2,6-cis-tetrahydropyran (THP) ring systems, as demonstrated by synthesis of the macrocyclic core to neopeltolide. Ultimately, we wish to apply this chemistry to de novo PKS pathways for rapid, reliable, and sustainable production of THP-bearing products like neopeltolide, and toward building SAR libraries. Additionally, a second study probed the specificity of the macrolactonizing thioesterase (TE) domain from the 6-deoxyerythronolide B (DEBS) biosynthetic pathway. This pathway is the paradigm for type-I PKS systems, and is responsible for producing the macrolide core of erythromycin. Our on-going research evaluates the limits of promiscuity within this specific catalytic domain, to characterize the structural elements required to accurately predict macrolactonization. The long-term goal of this study is to assess the potential applicability of DEBS TE as a generalized cyclization biocatalyst for combinatorial biochemistry and chemoenzymatic research.

Download or read book Studies in Polyketide Total Synthesis written by and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation will describe the development of a practical and scalable crotylation reaction with application toward the total syntheses of two polyketide-derived natural products: Zincophorin and Dictyostatin.

Download or read book Synthetic Studies Towards Berkelic Acid written by Zoe Elizabeth Wilson and published by . This book was released on 2010 with total page 339 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Medicinal Natural Products written by Paul M. Dewick and published by John Wiley & Sons. This book was released on 2002-01-03 with total page 524 pages. Available in PDF, EPUB and Kindle. Book excerpt: This guide covers classes of natural products in medicine, whether derived from plants, micro-organisms or animals. Structured according to biosynthetic pathway, it is written from a chemistry-based approach.

Download or read book Synthetic Studies on Bioactive Natural Products written by Anton El Khoury and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nature continues to provide a wide array of structurally novel, biologically active small molecules. This thesis describes synthetic studies on two such compounds. The approach used in each project are different. The first project involves a unique molecule that is produced by Nature in only trace quantities. We attempt to develop the first laboratory synthesis of the compound such that it could become available in sufficient amounts to study its biological properties in detail. In the second project, we work with a compound that is naturally abundant, yet has poor pharmacological properties. In that instance, we use synthesis to selectively modify its complex structure in ways that alter its properties while enabling conjugation to carrier proteins. Portimine is a marine-derived cyclic imine recently discovered as a selective inducer of apoptosis in cancer cells. Moreover, it showed markedly lower in vivo toxicity relative to other macrocycles in its class. Portimine's biological activities are reminiscent of pro-apoptotic biologics such as TRAIL (TNF-related apoptosis-inducing ligand) and TNF[alpha] (tumor necrosis factor alpha). No synthesis of portimine has been published and this work outlines the synthetic studies performed en route to the natural product as well as the exploration and development of novel methodologies along the way. Another natural product, epigallocatechin-3-gallate (EGCG), is a major catechin found in tea that has been shown to inhibit tau through disaggregation of fibrils. The synthesis of several EGCG analogs as well as the biological assays performed with the ultimate goal of developing an Alzheimer's therapeutic are described. Chapter one describes the development of a highly diastereo- and enantioselective Mukaiyama-Michael reaction for the synthesis of a key chiral intermediate utilized in the subsequent synthetic studies towards portimine. A stereochemical reassignment of the reported isomers of the desired structure is discussed aimed at the elimination of clear inconsistencies in the published reports. Both the racemic, as well as stereoselective synthesis, of both diastereomers are shown that once and for all establish the spectroscopic assignment of the products. Model studies of portimine including both the synthesis of thiophene-based as well as the more elaborate deoxygenated Diels-Alder precursor synthesized in just 3 steps from the published intermediate are reported as well. Optimization of the homoenolate cross-coupling as well as the development of the highly convergent route allowed for the rapid assembly of the chain containing all of the carbons present in portimine. Subsequent Diels-Alder studies as well as the challenges associated with utilizing an acyclic precursor provided useful information for the asymmetric synthesis of portimine. Chapter two describes the synthetic studies toward the natural product. Highly enantio- and diastereoselective aldol reaction as well as the alcohol-directed Narasaka-Prasad reaction allowed for the installation of the key sequence of stereocenters. Both halogenated as well as highly reactive dendralene Diels-Alder precursors have been synthesized which allowed for the in-depth studies of the cycloaddition conditions. The synthesis of a novel heterocycle provided access to the previously unknown motif that will be beneficial for the future syntheses of cyclic imine natural products. Chapter three discusses the synthesis of the EGCG analogs, and the biological studies associated with their potential as tau disaggregants. The development of the efficient click reaction assisted by copper-stabilizing Sharpless polytriazole ligand allowed for the synthesis of the conjugates of varied lengths. Subsequent nanoparticle conjugation showed the conservation of the biological activity as well as confirmed a previously hypothesized EGCG's mode of action. Diastereoselective B-ring derivatization not only allowed for the installation of the PEGylated linkers at the new position but also for structure-activity relationship studies on EGCG's D-ring shedding light on the importance of gallate phenols as well as the possibility for the installation of fluorine without sacrificing activity. Improved disaggregating activity of synthesized analogs showcased their promise as potential Alzheimer's therapeutics.

Download or read book Biotechnology and Biology of Trichoderma written by Vijai G. Gupta and published by Newnes. This book was released on 2014-02-17 with total page 569 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biotechnology and Biology of Trichoderma serves as a comprehensive reference on the chemistry and biochemistry of one of the most important microbial agents, Trichoderma, and its use in an increased number of industrial bioprocesses for the synthesis of many biochemicals such as pharmaceuticals and biofuels. This book provides individuals working in the field of Trichoderma, especially biochemical engineers, biochemists and biotechnologists, important information on how these valuable fungi can contribute to the production of a wide range of products of commercial and ecological interest. Provides a detailed and comprehensive coverage of the chemistry, biochemistry and biotechnology of Trichoderma, fungi present in soil and plants Includes most important current and potential applications of Trichoderma in bioengineering, bioprocess technology including bioenergy & biofuels, biopharmaceuticals, secondary metabolites and protein engineering Includes the most recent research advancements made on Trichoderma applications in plant biotechnology and ecology and environment

Download or read book Chemical and Biological Synthesis written by Nick J Westwood and published by Royal Society of Chemistry. This book was released on 2018-08-16 with total page 317 pages. Available in PDF, EPUB and Kindle. Book excerpt: Synthetic chemistry plays a central role in many areas of chemical biology; utilising recent case studies, the goal of Chemical and Biological Synthesis is to highlight the full impact that the preparation of novel reagents can have in chemical biology. Covering the synthetic approaches that can be applied across the whole field of chemical biology, this book provides synthetic chemists with the broader context to which their work contributes and the biological questions that can be addressed through it. An ideal guide for postgraduate students and researchers in synthetic organic chemistry and chemical biology, Chemical and Biological Synthesis introduces synthetic techniques and methods to those who wish to incorporate synthesis for the first time in their biology-focused research programmes.

Download or read book Studies Towards Total Synthesis of Polyketide Natural Products and Alkaloids written by Anastasia Hager and published by . This book was released on 2012 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: