Australia is home to some of the oldest continuously rainforested ecosystems on earth. These forests contain a rich diversity of unique flora that reflect their origins from ancestors that were once widespread on the supercontinent Gondwana. Although rainforests represent 3% of Australian native forests (36,000 km2) and cover only 0.024% of earths land area, they contain ~3,800 gymnosperm and angiosperm species from 187 families and 942 genera. This phylogenetically diverse flora contains a rich diversity of natural products. The antiquity of the Australian rainforest flora matches with ancient biosynthetic lineages, and this has resulted in their natural product chemistry being remarkably diverse. Only 10% of the rainforest species have been investigated, but these studies have yielded almost 2,400 constituents. This contribution discusses the diversity of Australian rainforest derived natural products in relation to current knowledge on the origins, phylogenetic diversification and dispersal of seed plants. Ancient lineages appear to be reservoirs of high chemical diversity, and this highlights Australia's rainforests as a living museum of natural product chemical diversity. This volume highlights key highly bioactive natural products that have been isolated from Australian rainforest species and discusses recent NMR spectroscopic methods that have been developed to help identify unique molecules in complex mixtures in Australian rainforest species. It also discusses the significant contribution that Australian rainforest derived natural products play in our understanding of worldwide seed plant chemical diversity.
This contribution provides a comprehensive review of the biologically active compounds present in 21 high-value medicinal and aromatic plant species from Malaysia, with a particular focus on their phytochemical diversity and biological activities. Several plants, including well-known species such as Eurycoma longifolia, Andrographis paniculata, Morinda citrifolia, Centella asiatica, and Moringa oleifera, have been designated as high-priority herbal products under Malaysia's National Key Economic Area (NKEA) in the Eleventh Malaysia Plan (RMK-11). Their significance extends beyond traditional uses in herbal medicine, as they are being recognized increasingly for their potential to contribute to the national economy and modern healthcare solutions. The compilation provided describes the pharmacological properties of these plants, highlighting their anti-inflammatory, antioxidant, antimicrobial, and cytotoxic activities, among others. Additionally, the aromatic plants Clinacanthus nutans, Cananga odorata, Citrus hystrix, and Polygonum minus are included in terms of their bioactive compounds produced and their potential therapeutic and industrial applications. By highlighting the relevant current research, this compilation aims to provide valuable insight for researchers, policymakers, and industry stakeholders, in terms of enhancing the understanding of both the therapeutic potential of these plants and their possible future contributions to healthcare and sustainable economic development.
Little prior attention has been paid to the use of bryophytes in the human diet as foods, cosmetics, and medicines, despite there being 23,000 species known worldwide. Some mosses and liverworts produce significant levels of terpenoids and phenolic compounds possessing characteristic odors and tastes, as well as exhibiting cytotoxic, antioxidant, muscle relaxant, anti-inflammatory, antiobesity, and many other activities. In addition, vitamin B2 and tocopherols, as well as prostaglandin-like highly unsaturated fatty acids are produced by these organisms. In this contribution, the distribution in bryophytes of terpenoids, aromatic compounds, and polyketides, having biological and pharmacological activity, and their possible uses as cosmetics and foods, and in drug development are discussed.
The distribution, chemistry, and molecular bioactivity of tiglianes are reviewed from the very beginning of the studies on these diterpenoids, summarizing their clinical and toxicological literature mostly in its more recent and controversial aspects, and critically analyzing various proposals for their biosynthesis.
A lichen is a symbiotic association composed of a primary mycobionts and one or more photobionts living mutualistically together, forming a distinct morphological entity beneficial to their partnership and to other associated fungi, photobionts, and bacteria that collectively make up the lichen biome. The taxonomic identification of a lichen species often requires determination of the primary mycobiont's secondary metabolites, the key morphological characteristics of the thallus, and how it relates to other lichen species as seen in DNA phylogeny. This chapter covers lichens and their bionts, taxonomic identification, and their chemical constituents as exemplified by what is found in lichen biomes, especially those endemic to North America. Extraction and isolation, as well as updates on dereplication methods using mass spectrometric GNPS and NMR spectroscopic spin network fingerprint procedures, and marker-based techniques to identify lichens are discussed. The isolation and structure elucidation of secondary metabolites of an endolichenic Penicillium species that produces bioactive compounds will be described in detail.
The development of efficient methods for dereplication has been critical in the re-emergence of the research in natural products as a source of drug leads. Current dereplication workflows rapidly identify already known bioactive secondary metabolites in the early stages of any drug discovery screening campaign based on natural extracts or enriched fractions. Two main factors have driven the evolution of natural products dereplication over the last decades. First, the availability of both commercial and public large databases of natural products containing the key annotations against which the biological and chemical data derived from the studied sample are searched for. Second, the considerable improvement achieved in analytical technologies (including instrumentation and software tools) employed to obtain robust and precise chemical information (particularly spectroscopic signatures) on the compounds present in the bioactive natural product samples. This chapter describes the main methods of dereplication, which rely on the combined use of large natural product databases and spectral libraries, alongside the information obtained from chromatographic, UV-Vis, MS, and NMR spectroscopic analyses of the samples of interest.
Plants are excellent chemists with an impressive capability of biosynthesizing a large variety of natural products (also known as secondary or specialized metabolites) to resist various biotic and abiotic stresses. In this chapter, 989 plant natural products and their ecological functions in plant-herbivore, plant-microorganism, and plant-plant interactions are reviewed. These compounds include terpenoids, phenols, alkaloids, and other structural types. Terpenoids usually provide direct or indirect defense functions for plants, while phenolic compounds play important roles in regulating the interactions between plants and other organisms. Alkaloids are frequently toxic to herbivores and microorganisms, and can therefore also provide defense functions. The information presented should provide the basis for in-depth research of these plant natural products and their natural functions, and also for their further development and utilization.
Neurotrophins (NGF, BDNF, NT3, NT4) can decrease cell death, induce differentiation, as well as sustain the structure and function of neurons, which make them promising therapeutic agents for the treatment of neurodegenerative disorders. However, neurotrophins have not been very effective in clinical trials mostly because they cannot pass through the blood-brain barrier owing to being high-molecular-weight proteins. Thus, neurotrophin-mimic small molecules, which stimulate the synthesis of endogenous neurotrophins or enhance neurotrophic actions, may serve as promising alternatives to neurotrophins. Small-molecular-weight natural products, which have been used in dietary functional foods or in traditional medicines over the course of human history, have a great potential for the development of new therapeutic agents against neurodegenerative diseases such as Alzheimer's disease. In this contribution, a variety of natural products possessing neurotrophic properties such as neurogenesis, neurite outgrowth promotion (neuritogenesis), and neuroprotection are described, and a focus is made on the chemistry and biology of several neurotrophic natural products.
This book describes a unique class of secondary metabolites, the mono- and dimeric naphthylisoquinoline alkaloids. They occur in lianas of the paleotropical Ancistrocladaceae and Dioncophyllaceae families, exclusively. Their unprecedented structures include stereogenic centers and rotationally hindered, and thus likewise stereogenic, axes. Extended recent investigations on six Ancistrocladus species from Asia, as reported in this review, shed light on their fascinating phytochemical productivity, with over 100 such intriguing natural products. This high chemodiversity arises from a likewise unique biosynthesis from acetate-malonate units, following a novel polyketidic pathway to plant-derived isoquinoline alkaloids. Some of the compounds show most promising antiparasitic activities. Likewise presented are strategies for the regio- and stereoselective total synthesis of the alkaloids, including the directed construction of the chiral axis.
The widespread utility of herbal products has been rising considerably worldwide, including both developed and developing countries, leading to the rapid growth of their availability in the United States and globally. This substantial increase in consumption of herbal products has witnessed the emergence of adverse effects upon oral administration of certain of these products, and thus has raised safety concerns. The adverse effects caused by the consumption of certain botanical medicines occur primarily as a result of the poor quality of plant raw materials or the finished products, which inherently may affect safety and/or efficacy. The poor quality of some herbal products can be attributed to a lack of proper quality assurance and quality control. A high demand for herbal products that surpasses production, combined with a desire for maximizing profits, along with a lack of rigorous quality control within some manufacturing facilities have led to the emergence of quality inconsistencies. The underlying causes for this involve the misidentification of plant species, or their substitution, adulteration, or contamination with harmful ingredients. Analytical assessments have revealed there to be frequent and significant compositional variations between marketed herbal products. The inconsistency of the quality of herbal products can be ascribed essentially to the inconsistency of the botanical raw material quality used to manufacture the products. Thus, the quality assurance and the quality control of the botanical raw materials is may contribute significantly to improving the quality and consistency of the quality of the end products. The current chapter focuses on the chemical evaluation of quality and consistency of herbal products, including botanical dietary supplements. Different techniques, instruments, applications, and methods used in identifying, quantifying, and generating chemical fingerprints and chemical profiles of the ingredients of the herbal products will be described. The strengths and weaknesses of the various techniques available will be addressed. Limitations of the other approaches including morphological or microscopic analysis and DNA-based analysis will be 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 8000 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.
In the world trade of medicinal plants, the naming of plants is fundamental to understanding which species are acceptable for therapeutic use. There are a variety of nomenclatural systems that are used, inclusive of common names, Latinized binomials, Galenic or pharmaceutical names, and pharmacopeial definitions. Latinized binomials are the primary system used for naming wild plants, but these alone do not adequately define medicinal plant parts. Each system has its specific applications, advantages, and disadvantages. The topic of medicinal plant nomenclature is discussed broadly by underscoring when and how varying nomenclatural systems should be used. It is emphasized that pharmacopeial definitions represent the only naming system that integrates plant identity, relevant plant parts, and the specific quality metrics to which a material must comply, thus affording the most appropriate identification method available for medicinal plant materials.
The Natural Herbal Products industry uses botanicals or herbs as raw materials for production of herbal products or dietary supplements. Recently, the demand for natural herbal products has increased tremendously and this has led to adulteration and to counterfeit herbal products. The present chapter deals with currently used molecular methods from "simple" single genomic regions to high-throughput whole genome or transcriptome sequencing methods used in the identification of botanicals.
Based on their current wide bioavailability, botanical dietary supplements have become an important component of the United States healthcare system, although most of these products have limited scientific evidence for their use. The most recent American Botanical Council Market Report estimated for 2020 a 17.3% increase in sales of these products when compared to 2019, for a total sales volume of $11,261 billion. The use of botanical dietary supplements products in the United States is guided by the Dietary Supplement Health and Education Act (DSHEA) from 1994, enacted by the U.S. Congress with the aim of providing more information to consumers and to facilitate access to a larger number of botanical dietary supplements available on the market than previously. Botanical dietary supplements may be formulated for and use only using crude plant samples (e.g., plant parts such as the bark, leaves, or roots) that can be processed by grinding into a dried powder. Plant parts can also be extracted with hot water to form an "herbal tea." Other preparations of botanical dietary supplements include capsules, essential oils, gummies, powders, tablets, and tinctures. Overall, botanical dietary supplements contain bioactive secondary metabolites with diverse chemotypes that typically are found at low concentration levels. These bioactive constituents usually occur in combination with inactive molecules that may induce synergy and potentiation of the effects observed when botanical dietary supplements are taken in their different forms. Most of the botanical dietary supplements available on the U.S. market have been used previously as herbal remedies or as part of traditional medicine systems from around the world. Their prior use in these systems also provides a certain level of assurance in regard to lower toxicity levels. This chapter will focus on the importance and diversity of the chemical features of bioactive secondary metabolites found in botanical dietary supplements that are responsible for their applications. Many of the active principles of botanical dietary substances are phenolics and isoprenoids, but glycosides and some alkaloids are also present. Biological studies on the active constituents of selected botanical dietary supplements will be discussed. Thus, the present chapter should be of interest for both members of the natural products scientific community, who may be performing development studies of the products available, as well as for healthcare professionals who are directly involved in the analysis of botanical interactions and evaluation of the suitability of botanical dietary supplements for human consumption.
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. This contribution covers recent reports of total syntheses involving as a key step a photocatalytic reaction. Among the selected examples, the photocatalytic processes proceed in a highly chemo-, regio-, and stereoselective manner, thereby allowing the rapid access to structurally complex architectures under light-driven conditions.
Pyrogallols (1,2,3-trihydroxybenzenes) are abundant in Nature, easily oxidized, and are central precursors to important natural products. The rich chemistry of their oxidized derivatives, the hydroxy-o-quinones, has been studied for over a century and still attracts the interest of the scientific community. Only in the last ten years have critical insights of pyrogallol chemistry from the mid-twentieth century been applied to modern natural product synthesis. Historical studies of pyrogallol chemistry, including [5+2], [4+2], and formal [5+5] cycloadditions are discussed here and reactivity guidelines established. The application and remarkable selectivity of these cycloadditions is then showcased in the recent syntheses of several fungal natural products, including dibefurin, epicolactone, the merocytochalasans, and preuisolactone A. The authors hope that this contribution will spark further interest in the fascinating chemistry of pyrogallols and natural products derived from them.
Natural products have made a crucial and unique contribution to human health, and this is especially true in the case of malaria, where the natural products quinine and artemisinin and their derivatives and analogues, have saved millions of lives. The need for new drugs to treat malaria is still urgent, since the most dangerous malaria parasite, Plasmodium falciparum, has become resistant to quinine and most of its derivatives and is becoming resistant to artemisinin and its derivatives. This volume begins with a short history of malaria and follows this 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. The volume then 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 other 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. The chapter thus ends by identifying over ten natural products with development potential as clinical antimalarial agents.
The phytochemistry of the fragrant infected heartwood of Aquilaria and Gyrinops species, agarwood (oud), is critically reviewed, highlighting the use of this remarkable natural raw material in perfumery. The chemistry of the two main groups of constituents of agarwood (sesquiterpenoids and chromones) is discussed, focusing particularly on the former structural type. The identities of the main key odorants of agarwood essential oil and of the smoke produced by heating the wood of agarwood are also discussed.
The original version of the book was inadvertently published with an incorrect series of formulas (197-199) in the formula scheme on Page 70 of Chapter 1, which has now been replaced with the correct formula (202). The erratum chapter has been updated with the changes and the correct presentation is given here
Medicinal plants of the genus Walsura (family Meliaceae) are native to tropical zones of a number of Asian countries, and have been used in systems of folk medicine. Several original research articles on Walsura species are available, but an overview highlighting the phytochemical and biological aspects of the compounds isolated to date is so far absent. Since the 1970s, phytochemical investigations on the genus Walsura have been undertaken, and more than 220 compounds from ten species have been identified. Natural products from Walsura species that have received the most attention are limonoids (114 compounds) and triterpenoids (72 compounds). Walsura limonoids have been characterized structurally as having diverse skeletons and more than 100 such compounds are new to the literature, while dammaranes, tirucallanes, and apotirucallanes are the main triterpenoid types from this genus. Other Walsura constituents comprise sesquiterpenoids, flavonoids, sterols, lignans, xanthones, and anthraquinones. Walsura species constituents have also been studied in natural product drug discovery screening programs. Many in vitro biological and some in vivo pharmacological investigations have been carried out on Walsura species isolated compounds. Walsura components display properties such as cancer cell cytotoxicity, antimicrobial, antidiabetes, anti-inflammatory, antioxidant, antifeedant, antifertility, ichthyotoxic, and neuroprotection activities.
