Progress in the Chemistry of Organic Natural Products – serie

The first contribution summarizes current trends in research on medicinal plants in Mexico with emphasis on work carried out at the authors' laboratories. The most relevant phytochemical and pharmacological profiles of a selected group of plants used widely for treating major national health problems are described. The second contribution provides a detailed survey of the so far reported literature data on the capacities of selected oxyprenylated phenylpropanoids and polyketides to trigger receptors, enzymes, and other types of cellular factors for which they exhibit a high degree of affinity and therefore evoke specifice responses. And the third contribution discusses aspects of endophytic actinobacterial biology and chemistry, including biosynthesis and total synthesis of secondary metabolites produced in culture. It also presents perspectives fo the future of microbial biodiscovery, with emphasis on the seondary metabolism of endophytic actinobacteria.

The first review describes examples of very promising compounds discovered from plants acquired from Africa, Southeast Asia, the Americas, and the Caribbean region with potential anticancer activity. These include plant secondary metabolites of the diphyllin lignan, penta[b]benzofuran, triterpenoid, and tropane alkaloid types. The second review presents 40 more erythrinan alkaloids, which were either new or were missed out in the last major reviews, bringing to a total of 154 known erythrinan alkaloids known to date. The reported pharmacological activities of the new and known alkaloids showed a greater bias towards central nervous system and related activities. Other prominent activities reported were antifeedant or insecticidal, cytotoxicity/anti­tumor/anti­cancer/estrogenic, antiprotozoal, antiinflammatory, antioxidant, antifungal and antiviral activities.

This volume comprises three reviews. The first describes isolation, structure determination, syntheses, and biochemistry of the low molecular weight compounds of the secretion of exocrine glands of termies with emphasis to pheromones and defensive compounds. The second review describes recent studies on isolation and structure elucidation of bioactive compounds involved in the life cycle and determination of the molecular mechanisms of the developmental events observed in higher plants. The third contribution reports on the current body of knowledge of African propolis, with a particular emphasis on its chemistry and biological activity.

This volume comprises three reviews. The first describes isolation, structure determination, syntheses, and biochemistry of the low molecular weight compounds of the secretion of exocrine glands of termies with emphasis to pheromones and defensive compounds. The second review describes recent studies on isolation and structure elucidation of bioactive compounds involved in the life cycle and determination of the molecular mechanisms of the developmental events observed in higher plants. The third contribution reports on the current body of knowledge of African propolis, with a particular emphasis on its chemistry and biological activity.

The book summarizes important aspects of cheminformatics that are relevant for natural product research. It highlights cheminformatics tools that help to match natural products with their respective biological targets or off-targets, and discusses the potential and limitations of this approach.

The book summarizes important aspects of cheminformatics that are relevant for natural product research. It highlights cheminformatics tools that help to match natural products with their respective biological targets or off-targets, and discusses the potential and limitations of this approach.

The first chapter in volume 111 summarizes research on the sesterterpenoids, which are known as a relatively small group of natural products. However, they express a variety of simple to complicated chemical structures. This chapter focuses on the chemical structures of sesterterpenoids and how their structures are synthesized in Nature. The second chapter is devoted to marine-derived fungi, which play an important role in the search for structurally unique secondary metabolites, some of which show promising pharmacological activities that make them useful leads for drug discovery. Marine natural product research in China in general has made enormous progress in the last two decades as described in this chapter on fungal metabolites. This contribution covers 613 new natural products reported from 2001 to 2017 from marine-derived fungi obtained from algae, sponges, corals, and other marine organisms from Chinese waters.

The first chapter in volume 111 summarizes research on the sesterterpenoids, which are known as a relatively small group of natural products. However, they express a variety of simple to complicated chemical structures. This chapter focuses on the chemical structures of sesterterpenoids and how their structures are synthesized in Nature. The second chapter is devoted to marine-derived fungi, which play an important role in the search for structurally unique secondary metabolites, some of which show promising pharmacological activities that make them useful leads for drug discovery. Marine natural product research in China in general has made enormous progress in the last two decades as described in this chapter on fungal metabolites. This contribution covers 613 new natural products reported from 2001 to 2017 from marine-derived fungi obtained from algae, sponges, corals, and other marine organisms from Chinese waters.

The first chapter describes the oldest method of communication between living systems in Nature, the chemical language. Plants, due to their lack of mobility, have developed the most sophisticated way of chemical communication. Despite that many examples involve this chemical communication process - allelopathy, there is still a lack of information about specific allelochemicals released into the environment, their purpose, as well as in-depth studies on the chemistry underground. These findings are critical to gain a better understanding of the role of these compounds and open up a wide range of possibilities and applications, especially in agriculture and phytomedicine. The most relevant aspects regarding the chemical language of plants, namely, kind of allelochemicals have been investigated, as well as their releasing mechanisms and their purpose, are described in this chapter.The second chapter is focused on the natural products obtained from Hypericum L., a genus of the family Hypericaceae within the dicotyledones. Hypericum has been valued for its important biological and chemical properties and its use in the treatment of depression and as an antibacterial has been well documented in primary literature and ethnobotanical reports. The present contribution gives a comprehensive summary of the chemical constituents and biological effects of this genus. A comprehensive account of the chemical constituents including phloroglucinol derivatives, xanthones, dianthrones, and flavonoids is included. These compounds show a diverse range of biological activities that include antimicrobial, cytotoxic, antidepressant-like, and antinociceptive effects.The third chapter addresses microtubule stabilizers, which are a mainstay in the treatment of many solid cancers and are often used in combination with molecularly targeted anticancer agents and immunotherapeutics.  The taccalonolides are a unique class of such microtubule stabilizers isolated from plants of Tacca species that circumvent clinically relevant mechanisms of drug resistance. Although initial reports suggested that the microtubule stabilizing activity of the taccalonolides is independent of direct tubulin binding, additional studies have found that potent C-22,23 epoxidated taccalonolides covalently bind the Aspartate 226 residue of β-tubulin and that this interaction is critical for their microtubule stabilizing activity. Some taccalonolides have demonstrated in vivo antitumor efficacy in drug-resistant tumor models with exquisite potency and long-lasting antitumor efficacy as a result of their irreversible target engagement. The recent identification of a site on the taccalonolide scaffold that is amenable to modification has provided evidence of the specificity of the taccalonolide-tubulin interaction and the opportunity to further optimize the targeted delivery of the taccalonolides to further improve their anticancer efficacy and potential for clinical development.

The first chapter describes the oldest method of communication between living systems in Nature, the chemical language. Plants, due to their lack of mobility, have developed the most sophisticated way of chemical communication. Despite that many examples involve this chemical communication process - allelopathy, there is still a lack of information about specific allelochemicals released into the environment, their purpose, as well as in-depth studies on the chemistry underground. These findings are critical to gain a better understanding of the role of these compounds and open up a wide range of possibilities and applications, especially in agriculture and phytomedicine. The most relevant aspects regarding the chemical language of plants, namely, kind of allelochemicals have been investigated, as well as their releasing mechanisms and their purpose, are described in this chapter.The second chapter is focused on the natural products obtained from Hypericum L., a genus of the family Hypericaceae within the dicotyledones. Hypericum has been valued for its important biological and chemical properties and its use in the treatment of depression and as an antibacterial has been well documented in primary literature and ethnobotanical reports. The present contribution gives a comprehensive summary of the chemical constituents and biological effects of this genus. A comprehensive account of the chemical constituents including phloroglucinol derivatives, xanthones, dianthrones, and flavonoids is included. These compounds show a diverse range of biological activities that include antimicrobial, cytotoxic, antidepressant-like, and antinociceptive effects.The third chapter addresses microtubule stabilizers, which are a mainstay in the treatment of many solid cancers and are often used in combination with molecularly targeted anticancer agents and immunotherapeutics.  The taccalonolides are a unique class of such microtubule stabilizers isolated from plants of Tacca species that circumvent clinically relevant mechanisms of drug resistance. Although initial reports suggested that the microtubule stabilizing activity of the taccalonolides is independent of direct tubulin binding, additional studies have found that potent C-22,23 epoxidated taccalonolides covalently bind the Aspartate 226 residue of β-tubulin and that this interaction is critical for their microtubule stabilizing activity. Some taccalonolides have demonstrated in vivo antitumor efficacy in drug-resistant tumor models with exquisite potency and long-lasting antitumor efficacy as a result of their irreversible target engagement. The recent identification of a site on the taccalonolide scaffold that is amenable to modification has provided evidence of the specificity of the taccalonolide-tubulin interaction and the opportunity to further optimize the targeted delivery of the taccalonolides to further improve their anticancer efficacy and potential for clinical development.

In this book, chemical studies are described mainly from literature reports appearing since 2000, inclusive of investigations performed by the present authors, on the diversity in secondary metabolites of Ligularia growing in the Hengduan Mountains area of China, focusing on eremophilane sesquiterpenoids and other metabolites. More than 100 Ligularia species and their related genera in the plant family Senecioneae plants (Cremanthodium, Cacalia, Senecio, and others) grow in East Asia. For many years, researchers have studied the chemical constituents of these plants, and terpenoids, flavonoids, steroids, alkaloids, and aromatic compounds have been isolated. Among these, in particular, numerous sesquiterpenoids were reported. Within this book terpenoids and aromatic compounds (total 1049), both previously unknown and known, are presented. Finally, genetic studies and synthesis investigations are briefly reviewed.

In this book, chemical studies are described mainly from literature reports appearing since 2000, inclusive of investigations performed by the present authors, on the diversity in secondary metabolites of Ligularia growing in the Hengduan Mountains area of China, focusing on eremophilane sesquiterpenoids and other metabolites.

This book describes current understandings and recent progress in four areas: in the first one, the cytochalasans, a group of fungal derived natural products characterized by a perhydro-isoindolone core fused with a macrocyclic ring are shown to exhibit high structural diversity and a broad spectrum of bioactivities. The second one is dedicated to a description of bioactive compounds from the medicinal plants of Myanmar, the third one is dedicated to new structure elucidation techniques in the field of sesquiterpenes. The last one discusses the endogenous natural products that are produced by human cells including endogenous amines, steroids, and fatty acid derived natural products. The co-metabolism and natural product production of the human microbiome is also described including tryptophan, bile acids, choline, and cysteine.

This book describes current understandings and recent progress in four areas: in the first one, the cytochalasans, a group of fungal derived natural products characterized by a perhydro-isoindolone core fused with a macrocyclic ring are shown to exhibit high structural diversity and a broad spectrum of bioactivities. The second one is dedicated to a description of bioactive compounds from the medicinal plants of Myanmar, the third one is dedicated to new structure elucidation techniques in the field of sesquiterpenes. The last one discusses the endogenous natural products that are produced by human cells including endogenous amines, steroids, and fatty acid derived natural products. The co-metabolism and natural product production of the human microbiome is also described including tryptophan, bile acids, choline, and cysteine.

This book describes current understandings and recent progress into a varied group of natural products. In the first chapter the role that total synthesis may play in revising the structures proposed for decanolides, which are ten-membered lactones found primarily in fungi, frogs, and termites is presented. The following chapter presents the development of the intriguing plant-derived sesquiterpene lactone, thapsigargin, a potent inhibitor of the enzyme, SERCA (sarco-endoplasmic Ca2+ ATPase), which has potential as a lead compound to treat cancer. The third chapter covers the potential of various plant phenolic compounds for treating the tropical and sub-tropical infectious disease, leishmaniasis. In addition the volume presents recent advances related to the plant alkaloid, cryptolepine, which is of particular interest as a lead for the treatment of malaria, trypanosomiasis, and cancer.

This book describes current understandings and recent progress into a varied group of natural products. In the first chapter the role that total synthesis may play in revising the structures proposed for decanolides, which are ten-membered lactones found primarily in fungi, frogs, and termites is presented. The following chapter presents the development of the intriguing plant-derived sesquiterpene lactone, thapsigargin, a potent inhibitor of the enzyme, SERCA (sarco-endoplasmic Ca2+ ATPase), which has potential as a lead compound to treat cancer. The third chapter covers the potential of various plant phenolic compounds for treating the tropical and sub-tropical infectious disease, leishmaniasis. In addition the volume presents recent advances related to the plant alkaloid, cryptolepine, which is of particular interest as a lead for the treatment of malaria, trypanosomiasis, and cancer.

This volume describes several highly diverse subjects: Chapter 1 explores marine biodiscovery of the North-eastern Atlantic off the coast of Ireland as a model for best practice in research. The second chapter investigates Brazilian Chemical Ecology and examples of insect-plant communication studies that are mediated by natural products demonstrate the beautiful interconnectedness of species in a biome. Our third chapter comprises the advances in the science of the sesquiterpene quinone, perezone, which in 1852 was the first natural product isolated in crystalline form in the New World. The last two chapters are from a Vietnamese group and the first of these follows the phytochemistry, pharmacology, and ethnomedical uses of the genus Xanthium, which produces interesting sulfur and nitrogen containing natural products. Finally, the genus Desmos is discussed, where an overview of its constituent natural products and their in vitro pharmacological potential is described.

This volume describes several highly diverse subjects: Chapter 1 explores marine biodiscovery of the North-eastern Atlantic off the coast of Ireland as a model for best practice in research. The second chapter investigates Brazilian Chemical Ecology and examples of insect-plant communication studies that are mediated by natural products demonstrate the beautiful interconnectedness of species in a biome. Our third chapter comprises the advances in the science of the sesquiterpene quinone, perezone, which in 1852 was the first natural product isolated in crystalline form in the New World. The last two chapters are from a Vietnamese group and the first of these follows the phytochemistry, pharmacology, and ethnomedical uses of the genus Xanthium, which produces interesting sulfur and nitrogen containing natural products. Finally, the genus Desmos is discussed, where an overview of its constituent natural products and their in vitro pharmacological potential is described.

This volume begins with a short history of malaria and follows with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment, and then describes quinine’s biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine’s structure. It also covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of additional natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature’s combinatorial library is challenging, it is very likely to yield new antimalarial drugs. This book thus ends byidentifying ten natural products with development potential as clinical antimalarial agents.

This volume begins with a short history of malaria and follows with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment, and then describes quinine’s biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine’s structure. It also covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of additional natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature’s combinatorial library is challenging, it is very likely to yield new antimalarial drugs. This book thus ends byidentifying ten natural products with development potential as clinical antimalarial agents.

This volume consists of four chapters that cover a structurally diverse range of naturally occurring compounds. Chapter 1 delves into the chemistry of pyrogallols and their oxidized products, the hydroxy-o-quinones, including their role in cycloaddition reactions in the chemical synthesis of several fungal metabolites. Chapter 2 provides an in-depth description of the constituents of agarwood essential oil and smoke samples that are used in the perfumery industry, with an emphasis on the sesquiterpenoid and chromones constituents so far known. Chapter 3 discusses the defensive chemical ecology of two North American newt species that both produce tetrodotoxin, a well-known neurotoxin that causes paralysis and death in metazoans by disrupting electrical signals in the nerves and muscles. Chapter 4 discusses the limonoids and triterpenoids from the genus Walsura of the plant family Meliaceae, of which a number of species are utilized in several southeastern Asian countries in systems of folk medicine.

This volume consists of four chapters that cover a structurally diverse range of naturally occurring compounds. Chapter 1 delves into the chemistry of pyrogallols and their oxidized products, the hydroxy-o-quinones, including their role in cycloaddition reactions in the chemical synthesis of several fungal metabolites. Chapter 2 provides an in-depth description of the constituents of agarwood essential oil and smoke samples that are used in the perfumery industry, with an emphasis on the sesquiterpenoid and chromones constituents so far known. Chapter 3 discusses the defensive chemical ecology of two North American newt species that both produce tetrodotoxin, a well-known neurotoxin that causes paralysis and death in metazoans by disrupting electrical signals in the nerves and muscles. Chapter 4 discusses the limonoids and triterpenoids from the genus Walsura of the plant family Meliaceae, of which a number of species are utilized in several southeastern Asian countries in systems of folk medicine.

This book describes a unique class of secondary metabolites, the mono- and dimeric-naphthylisoquinoline alkaloids. They exclusively occur in lianas of the palaeotropical Ancistrocladaceae and Dioncophyllaceae plant families. Their unprecedented structures include stereogenic centers and rotationally hindered, and therefore stereogenic, axes. Extended recent investigations on six Ancistrocladus species from Asia, as reported in this contribution, shed light on their fascinating phytochemical productivity, with over 100 intriguing natural products. This high chemodiversity arises from a similarly unique biosynthesis from acetate-malonate units, following a novel polyketidic pathway to plant-derived isoquinoline alkaloids. Some of the compounds show most promising anti-parasitic activities. Additionally, strategies for the regio- and stereoselective total synthesis of the alkaloids, including the directed construction of the chiral axis, are also presented.

This book describes a unique class of secondary metabolites, the mono- and dimeric-naphthylisoquinoline alkaloids. They exclusively occur in lianas of the palaeotropical Ancistrocladaceae and Dioncophyllaceae plant families. Their unprecedented structures include stereogenic centers and rotationally hindered, and therefore stereogenic, axes. Extended recent investigations on six Ancistrocladus species from Asia, as reported in this contribution, shed light on their fascinating phytochemical productivity, with over 100 intriguing natural products. This high chemodiversity arises from a similarly unique biosynthesis from acetate-malonate units, following a novel polyketidic pathway to plant-derived isoquinoline alkaloids. Some of the compounds show most promising anti-parasitic activities. Additionally, strategies for the regio- and stereoselective total synthesis of the alkaloids, including the directed construction of the chiral axis, are also presented.

This book presents recent reports of total syntheses involving a photocatalytic reaction as a key step in the methodology. Modern photocatalysis has proven its generality for the development and functionalization of native functionalities. To date, the field has found broad applications in diverse research areas, including the total synthesis of natural products. Among the selected examples presented in this book, it highlights how the photocatalytic process proceeds in a highly chemo-, regio-, and stereoselective manner, thereby allowing the rapid access to structurally complex architectures under light-driven conditions.

This book presents recent reports of total syntheses involving a photocatalytic reaction as a key step in the methodology. Modern photocatalysis has proven its generality for the development and functionalization of native functionalities. To date, the field has found broad applications in diverse research areas, including the total synthesis of natural products. Among the selected examples presented in this book, it highlights how the photocatalytic process proceeds in a highly chemo-, regio-, and stereoselective manner, thereby allowing the rapid access to structurally complex architectures under light-driven conditions.

The present volume is the third in a trilogy that documents naturally occurring organohalogen compounds, bringing the total number — from fewer than 25 in 1968 — to approximately 8,000 compounds to date. Nearly all of these natural products contain chlorine or bromine, with a few containing iodine and, fewer still, fluorine. Produced by ubiquitous marine (algae, sponges, corals, bryozoa, nudibranchs, fungi, bacteria) and terrestrial organisms (plants, fungi, bacteria, insects, higher animals) and universal abiotic processes (volcanos, forest fires, geothermal events), organohalogens pervade the global ecosystem. Newly identified extraterrestrial sources are also documented.  In addition to chemical structures, biological activity, biohalogenation, biodegradation, natural function, and future outlook are presented.

The present volume is the third in a trilogy that documents naturally occurring organohalogen compounds, bringing the total number — from fewer than 25 in 1968 — to approximately 8,000 compounds to date. Nearly all of these natural products contain chlorine or bromine, with a few containing iodine and, fewer still, fluorine. Produced by ubiquitous marine (algae, sponges, corals, bryozoa, nudibranchs, fungi, bacteria) and terrestrial organisms (plants, fungi, bacteria, insects, higher animals) and universal abiotic processes (volcanos, forest fires, geothermal events), organohalogens pervade the global ecosystem. Newly identified extraterrestrial sources are also documented.  In addition to chemical structures, biological activity, biohalogenation, biodegradation, natural function, and future outlook are presented.

This volume highlights some recent developments on plants used widely as botanical dietary supplements and herbal medicines, especially in terms of knowledge of the chemical types and diverse biological activities of their constituents, as well as laboratory approaches for their quality control and taxonomic identification. In the first chapter, the biologically active secondary metabolites are described of selected botanicals that have a wide current use in the United States, with recent information provided also on their in vitro and in vivo biological activities. The second chapter constitutes an updated survey of the different chromatographic, spectroscopic, and metabolomics techniques that can be utilized for the quality control of botanical products. The penultimate chapter covers different nomenclatural systems that are of use for the taxonomic identification of source plants used in botanical products. Finally, deoxyribonucleic acid molecular barcoding techniques for the identification for plants used as dietary supplements are covered.