Alkaloids: Chemistry and Biology最新文献

Of Nature's nearly 3000 unique monoterpene indole alkaloids derived from tryptophan, those members belonging to the Aspidosperma and Strychnos families continue to impact the fields of natural products (i.e., isolation, structure determination, biosynthesis) and organic chemistry (i.e., chemical synthesis, methodology development) among others. This review covers the biological activity (Section 2), biosynthesis (Section 3), and synthesis of both classical and novel Aspidosperma (Section 4), Strychnos (Section 5), and selected bis-indole (Section 6) alkaloids. Technological advancements in genetic sequencing and bioinformatics have deepened our understanding of how Nature assembles these intriguing molecules. The proliferation of innovative synthetic strategies and tactics for the synthesis of the alkaloids covered in this review, which include contributions from over fifty research groups from around the world, are a testament to the creative power and technical skills of synthetic organic chemists. To be sure, Nature-the Supreme molecular architect and source of a dazzling array of irresistible chemical logic puzzles-continues to inspire scientists across multiple disciplines and will certainly continue to do so for the foreseeable future.

While the use of ergot alkaloids in folk medicine has been practiced for millennia, systematic investigations on their therapeutic potential began about 100 years ago. Subsequently, Albert Hofmann's discovery of lysergic acid diethylamide (LSD) and its intense psychedelic properties garnered worldwide attention and prompted further studies of this compound class. As a result, several natural ergot alkaloids were discovered and unnatural analogs were synthesized, and some were used to treat an array of maladies, including Alzheimer's and Parkinson's disease. While LSD was never commercially approved, recent clinical studies have found it can be an innovative and effective treatment option for several psychiatric disorders. Ongoing biosynthetic and total synthetic investigations aim to understand the natural origins of ergot alkaloids, help develop facile means to produce these natural products and enable their continued use as medicinal chemistry lead structures. This review recounts major developments over the past 20 years in biosynthetic, total synthetic, and pharmaceutical studies. Many ergot alkaloid biosynthetic pathways have been elucidated, with some of them subsequently applied toward "green" syntheses. New chemical methodologies have fostered a fast and efficient access to the ergoline scaffold, prompting some groups to investigate biological properties of natural product-like ergot alkaloids. Limited pharmaceutical applications have yet to completely bypass the undesirable side effects of ergotism, suggesting further studies of this drug class are likely needed and will potentially harness major therapeutic significance.

Lamellarins are marine alkaloids containing fused 14-phenyl-6H-[1]benzopyrano[4',3':4,5]pyrrolo[2,1-a]isoquinoline or non-fused 3,4-diarylpyrrole-2-carboxylate ring systems. To date, more than 50 lamellarins have been isolated from a variety of marine organisms, such as mollusks, tunicates, and sponges. Many of them, especially fused type I lamellarins, exhibit impressive biological activity, such as potent cytotoxicity, topoisomerase I inhibition, protein kinases inhibition, and anti-HIV-1 activity. Due to their useful biological activity and limited availability from natural sources, a number of synthetic methods have been developed. In this chapter, we present an updated and comprehensive review on lamellarin alkaloids summarizing their isolation, synthesis, and biological activity.

The tryptamine-derived polycyclic bridged bioactive indole alkaloids subincanadines A-G were isolated in 2002 by Ohsaki and coworkers from the bark of the Brazilian medicinal plant Aspidosperma subincanum. Kobayashi proposed that subincanadines D-F could be biosynthetically resulting from stemmadenine via two different pathways and, furthermore, that the subincanadines A-C could be biogenetically resulting from subincanadines D and E. Kam and coworkers, in their focused efforts, isolated five indole alkaloids from Malaysian Kopsia arborea species, namely valparicine, apparicine, arboridinine, arborisidine, and arbornamine in combination with subincanadine E. On the basis of structural features, it has been proposed and proved in some examples that subincanadine E is a biogenetic precursor of these five different bioactive indole alkaloids bearing complex structural architectures. All important information on isolation, characterization, bioactivity, probable biogenetic pathways, and more specifically racemic and enantioselective total synthesis of subincanadine alkaloids and their biogenetic congeners are summarized in the present chapter. Special importance is given to the total synthesis and the synthetic strategies intended therein, comprising a set of main reactions.

The manzamine alkaloids are absolutely one of the most fascinating marine natural products. The representative manzamine alkaloids, manzamines A-C, were isolated from a marine sponge Haliclona sp. collected off Cape Manzamo, Okinawa, Japan. The manzamine alkaloids are a unique class of alkaloids possessing a characteristic heterocyclic system, and exhibit a diverse range of bioactivities including cytotoxicity, antimicrobial activity, antimalarial activity, antiviral and antiinflammatory activities, antiinsecticidal activity, and proteasome inhibitory activity. About 100 manzamine alkaloids have been isolated from more than 16 species of marine sponges belonging to 5 families. The unusual ring systems, an intriguing suggested biogenetic pathway, and promising biological activities of manzamine alkaloids have attracted great interest as challenging targets for the total synthesis. This review is the continuation of the previous review published in volume 60 of The Alkaloids and covers isolation, structure elucidation, biosynthesis and biogenesis, chemical synthesis, and biological activity of manzamine alkaloids reported from 2003 to 2018.