Progress in the chemistry of organic natural products最新文献

The combination of traditional knowledge of medicinal plants with scientific rationale has yielded positive results in recent years. Bioactive compounds isolated from herbaceous plants have long been used as drugs that benefit human health, as well as providing useful compounds for drug development lead compound optimization. This chapter aims to provide a systematic overview of the structural types of Desmos secondary metabolites, along with their biological potential. Various chromatographic and spectroscopic methods have been utilized for isolating, purifying, and elucidating the structures of compounds from Desmos species. From 1982 to the present time, more than 200 metabolites have been isolated from members of this genus. Desmos spp. constituents include terpenoids, phytosterols, polyoxygenated cyclohexanes and cyclohexenes, oxepinones, fatty acids, with flavonoids, alkaloids, and miscellaneous phenols being the predominant compounds. The essential oils of Desmos species have also been investigated. Both crude plant extracts and isolated compounds from this genus have been evaluated for their biological activities. Desmos constituents have been found to exhibit cytotoxic, antimicrobial, antioxidative, anti-inflammatory, and aromatase and NFAT transcriptive inhibition effects.

Herbaceous annual plants of the genus Xanthium are widely distributed throughout the world and have been employed medicinally for millennia. This contribution aims to provide a systematic overview of the diverse structural classes of Xanthium secondary metabolites, as well as their pharmacological potential. On searching in various reference databases with a combination of three keywords "Xanthium", "Phytochemistry", and "Pharmacology", relevant publications have been obtained subsequently. From the 1950s to the present, phytochemical investigations have focused mainly on 15 Xanthium species, from which 300 compounds have been isolated and structurally resolved, primarily using NMR spectroscopic methodology. Xanthium constituents represent several secondary metabolite types, including simple phenols, sulfur and nitrogen-containing compounds, lignans, sterols, flavonoids, quinones, coumarins, and fatty acids, with terpenoids being the most common of these. Among the 174 terpenoids characterized, xanthanolide sesquiterpenoids are abundant, and most of the compounds isolated containing sulfur were found to be new in Nature. The ethnomedical uses of Xanthium crude extracts are supported by the in vitro and in vivo effects of their constituents, such as cytotoxicity, antioxidant, antibacterial, antifungal, antidiabetes, and hepatoprotective activities. Toxicological results suggest that Xanthium plant extracts are generally safe for use. In the future, additional phytochemical investigations, along with further assessments of the biological profiles and mechanism of action studies of the components of Xanthium species, are to be expected.

The most significant new techniques that have been used in the twenty-first century for the structure elucidation of sesquiterpenes and some derivatives are reviewed in this chapter. A distinctive feature of these methodologies is the combination of accurate experimental measurements with theoretical data obtained by molecular modeling calculations that allow to visualize, understand, and quantify many structural characteristics. This has been the case for NMR spectroscopy, which has expanded its potential for solving complex structural problems by means of comparison with quantum mechanical molecular models. Ab initio and density functional theory calculations of chemical shifts, coupling constants, and residual chemical shift anisotropies have played important roles in the solution of many structures of sesquiterpenes. The assignments of their absolute configurations by evaluation of calculated and experimental chiroptical properties as electronic and vibrational circular dichroism are also reviewed. This chapter also includes the use of X-ray diffraction analysis with emphasis on calculations of the Flack and Hooft parameters, which are applicable to all molecules that crystallize in non-centrosymmetric space groups. The accurate molecular models of sesquiterpenes, validated by concordance with their experimental properties, are nowadays essential for the interpretation of the effects of these natural products on biological systems.

This chapter covers a sesquiterpene quinone, commonly named perezone. This molecule is documented as the first secondary metabolite isolated in crystalline form in the New World in 1852. An introduction, with its structure, the IUPAC nomenclature, and the most recent physical and spectroscopic characterizations are firstly described initially. Alongside this, a timeline and scheme with summarized information of the history of this molecule is given including the "Códice Badiano de la Cruz, 1552, highlighting the year of its isolation culminating with information up to 2005. Subsequently, in a chronological order the most recent advances of the target molecule are included and organized in subsections covering the last 15-year period 2006-2020. Finally, recently submitted contributions from the laboratory of the authors are described. It is important to note that the details provided highlight the importance and relevance of perezone.

The term "marine biodiscovery" has been recently been adopted to describe the area of marine natural products dedicated to the search of new drugs. Several maritime countries such as Australia, New Zealand, South Korea, and Japan as well as some European countries have invested significantly in this area of research over the last 50 years. In the late 2000s, research in this field has received significant interest and support in Ireland for exploring new marine bioresources from the nutrient-rich waters of the Northeastern Atlantic Ocean. Despite undeniable success exemplified by the marketing of new drugs, especially in oncology, the integration of new technical but also environmental aspects should be considered. Indeed, global change, particularly in our oceans, such as climate change, biodiversity loss, and the emergence of microbial pathogens, not only affects the environment but ultimately contributes to social inequalities. In this contribution, new avenues and best practices are proposed, such as the development of biorepositories and shared data for the future of marine biodiscovery research. The extension of this type of scientific work will allow humanity to finally make the optimum use of marine bioresources.

Secondary metabolites (SM) from organisms have served medicinal chemists over the past two centuries as an almost inexhaustible pool of new drugs, drug-like skeletons, and chemical probes that have been used in the "hunt" for new biologically active molecules with a "beneficial effect on human mind and body." Several secondary metabolites, or their derivatives, have been found to be the answer in the quest to search for new approaches to treat or even eradicate many types of diseases that oppress humanity. A special place among SM is occupied by lignans and neolignans. These phenolic compounds are generated biosynthetically via radical coupling of two phenylpropanoid monomers, and are known for their multitarget activity and low toxicity. The disadvantage of the relatively low specificity of phenylpropanoid-based SM turns into an advantage when structural modifications of these skeletons are made. Indeed, phenylpropanoid-based SM previously have proven to offer great potential as a starting point in drug development. Compounds such as Warfarin^® (a coumarin-based anticoagulant) as well as etoposide and teniposide (podophyllotoxin-based anticancer drugs) are just a few examples. At the beginning of the third decade of the twenty-first century, the call for the treatment of more than a dozen rare or previously "neglected" diseases remains for various reasons unanswered. Leishmaniasis, a neglected disease that desperately needs new ways of treatment, is just one of these. This disease is caused by more than 20 leishmanial parasites that are pathogenic to humans and are spread by as many as 800 sandfly species across subtropical areas of the world. With continuing climate changes, the presence of Leishmania parasites and therefore leishmaniasis, the disease caused by these parasites, is spreading from previous locations to new areas. Thus, leishmaniasis is affecting each year a larger proportion of the world's population. The choice of appropriate leishmaniasis treatment depends on the severity of the disease and its form of manifestation. The success of current drug therapy is often limited, due in most cases to requiring long hospitalization periods (weeks to months) and the toxicity (side effects) of administered drugs, in addition to the increasing resistance of the parasites to treatment. It is thus important to develop new drugs and treatments that are less toxic, can overcome drug resistance, and require shorter periods of treatment. These aspects are especially important for the populations of developing countries. It was reported that several phenylpropanoid-based secondary metabolites manifest interesting antileishmanial activities and are used by various indigenous people to treat leishmaniasis. In this chapter, the authors shed some light on the various biological activities of phenylpropanoid natural products, with the main focus being on their possible applications in the context of antileishmanial treatment.

Ten-membered lactones are commonly observed structures of natural products. They are mostly fungal metabolites, which often act as plant pathogens, but recently ten-membered lactones were identified as pheromones of frogs and termites. Although modern spectroscopic methods are nowadays routinely used to elucidate the structure of natural products, structural assignments of ten-membered lactones often remain incomplete or are surprisingly often erroneous. Most errors concern the absolute configuration. The examples discussed in this chapter demonstrate that enantioselective total synthesis is not only an efficient tool for corroborating or revising a proposed structure, but that the synthesis of different stereoisomers as references for gas chromatographic investigations can be a vital part of the structure elucidation process if only minute amounts of material are available. As a method of outstanding importance for the synthesis of ten-membered lactones olefin metathesis has emerged. Most of the examples discussed herein use one or more olefin metathesis reactions as key steps.

Natural products are a class of chemical compounds that are biosynthesized by living organisms, including humans. Endogenous natural products are produced by human cells as well as by the human microbiome. This contribution describes the current understanding and recent progress made on endogenous natural products that are produced by human cells, including amines, steroids, and fatty acid-derived natural products. The co-metabolism and natural product produced by the human microbiome will also be described, including the involvement of tryptophan, bile acids, choline, and cysteine. New strategies and technologies have been introduced that can be applied to identify and characterize those natural products produced by the human microbiome in terms of their composition and physiological function.

Myanmar is a country with rich natural resources and of these, medicinal plants play a vital role in the primary health care of its population. The people of Myanmar have used their own system of traditional medicine inclusive of the use of medicinal plants for 2000 years. However, systematic and scientific studies have only recently begun to be reported. Researchers from Japan, Germany, and Korea have collaborated with researchers in Myanmar on medicinal plants since 2000. During the past two decades, over 50 publications have been published in peer-reviewed journals. Altogether, 433 phytoconstituents, including 147 new and 286 known compounds from 26 plant species consisting of 29 samples native to Myanmar, have been collated. In this contribution, phytochemical and biological investigations of these plants, including information on traditional knowledge are compiled and discussed.