Securinega alkaloids have attracted immense attention from the phytochemical, synthetic, and pharmacological communities owing to their structural diversity and intriguing biological activities. Predominantly found in the genera Flueggea, Phyllanthus, Margaritaria, and Zygogynum, these alkaloids display a remarkable range of molecular architectures derived from the monomeric tetracyclic core consisting of the α,β-γ,δ-unsaturated ester moiety and the tertiary alkyl amine group. Their biosynthetic elaboration through oxidation, rearrangement, and oligomerization gives rise to an extraordinary chemical diversity spanning monomeric, dimeric, trimeric, and even higher oligomeric forms with varying oxidation states. This chapter provides a comprehensive overview of the isolation and structure elucidation of securinega alkaloids and recent (2014-2025) discoveries related to their biosynthesis, chemical synthesis, and biological evaluations. Particular emphasis is placed on recent discoveries, including the synthesis of oxidized, rearranged, and dimerized congeners, and newly uncovered biosynthetic enzymes that illuminate the molecular logic underlying scaffold assembly. The chapter also summarizes emerging insights into their pharmacological properties, including cytotoxic, neurotropic, and anti-inflammatory activities. Collectively, these advances not only clarify the intricate biogenetic origins and chemical synthesis of the securinega family but also establish a foundation for future exploration of their chemical biology and potential therapeutic applications.
Marine natural products have attracted considerable attention owing to their diverse biological activities and unique structural features. Among them, the dragmacidin alkaloids represent a structurally intriguing family of marine-derived natural products. These alkaloids exhibit a wide range of biological activities, including anticancer and antimicrobial activities, which have stimulated significant interest from both the chemical and biological communities. Structurally, they are characterized by highly functionalized bisindole frameworks in which two indole units are connected via a piperazine, pyrazine, or pyrazinone ring, and can be classified into three categories based on the nature of the linking unit: (i) dragmacidin and dragmacidins A, B, C, I, J, and didebromodragmacidin, featuring a piperazine linker; (ii) dragmacidins D, E, and F, containing a pyrazinone linker; and (iii) dragmacidins G and H, incorporating a pyrazine linker. These structural features pose formidable challenges for chemical synthesis, and consequently, the dragmacidin family has served as an important platform for the development of new synthetic strategies. In this chapter, we provide a comprehensive overview of the dragmacidin alkaloids, focusing on their isolation, structural features, biological activities, and synthetic studies.
Natural products containing five-membered nitrogen heterocycles, such as imidazole, oxazole, and thiazole rings, belong to a significant class of naturally occurring heterocyclic alkaloids. These are widely distributed in terrestrial plants, animals, marine invertebrates, and microorganisms. The complexity and diversity of the molecular architectures, as well as the inherently promising biological activities, endow these alkaloids with ideal targets of chemical synthesis and potent application in the discovery of new drugs. In this review, the latest research on the occurrence, isolation, structural characterization, biological activity, chemical synthesis, and state-of-the-art synthetic biology of these imidazole-, oxazole-, and thiazole-containing natural products was summarized. All alkaloids were classified into the corresponding subgroups according to common structural features or biological origins, with a view to convenience and rationality.
Marine organisms are a valuable source of lead compounds for drug development, and basic research. This field has been active for nearly half a century. However, because of their unique structures and poor chemical stability, it is difficult to achieve a sustainable, large-scale supply of marine natural products and thus, their use in drug development is rare. Renieramycin was first reported in 1982 by Fricke and Faulkner as a trace secondary metabolite from the blue sponge Reniera sp. Dimeric 1,2,3,4-tetrahydroisoquinoline derivatives, such as renieramycins, have attracted attention as novel anticancer agents. Therefore, challenges related to chemical stability and transformations, as well as development of total syntheses were overcome. Several excellent reviews on renieramycin marine natural products have been published. Research in the renieramycin family has been developed based on the results of various previous studies on saframycin, an antibiotic discovered from the Actinomycete Streptomyces lavendulae No. 314. In this review, we will introduce from a new perspective the results of ongoing efforts in the medicinal chemistry. We will explore the discovery, chemical transformation, total synthesis, and structure-activity relationships of renieramycin marine natural products, highlighting unexpected findings that emerged during the research process.1.
The pyrazole and indazole alkaloids include two different but related groups of naturally occurring substances with interesting structural variations and their biological properties are obtained from the secondary metabolites. In the present book chapter we describe the chemistry and biology of these alkaloids, including their biosynthetic pathway, isolation, structural properties, and variety of biological effects. An overview of the separation and structural elucidation of pyrazole and indazole alkaloids from several natural sources is presented at the beginning, demonstrating the diversity of these molecules across the kingdoms of plants. We also look at synthetic approaches to these structures. The main focus is on the biological activities of pyrazole and indazole alkaloids, which include pharmacological activities such as antibacterial, anti-inflammatory, and anticancer properties. A thorough review of the relevant literature is presented, providing insight into the essential structural motifs that govern their interactions with biological targets. In addition, the possible medicinal uses of these alkaloids are examined, highlighting their importance in the search for new drugs. Thus, the present chapter provides a comprehensive analysis of pyrazole and indazole alkaloids with an emphasis on their chemical structures and biological activities. It serves as a valuable resource for professionals in pharmacology and drug development, offering insights into the potential therapeutic applications of these compounds. By describing the intricate relationship between the chemistry and biology of these alkaloids, the chapter contributes to the field of natural product chemistry and to the discovery and synthesis of new drugs and treatments. This synthesis of current knowledge furthers scientific understanding and underscores the importance of alkaloids in medical research and pharmaceutical innovation.
