Alkaloids: Chemistry and Biology最新文献

Naphthylisoquinoline alkaloids are a fascinating class of natural biaryl compounds. They show characteristic mono- and dimeric scaffolds, with chiral axes and stereogenic centers. Since the appearance of the last comprehensive overview on these secondary plant metabolites in this series in 1995, the number of discovered representatives has tremendously increased to more than 280 examples known today. Many novel-type compounds have meanwhile been discovered, among them naphthylisoquinoline-related follow-up products like e.g., the first seco-type (i.e., ring-opened) and ring-contracted analogues. As highlighted in this review, the knowledge on the broad structural chemodiversity of naphthylisoquinoline alkaloids has been decisively driven forward by extensive phytochemical studies on the metabolite pattern of Ancistrocladus abbreviatus from Coastal West Africa, which is a particularly "creative" plant. These investigations furnished a considerable number of more than 80-mostly new-natural products from this single species, with promising antiplasmodial activities and with pronounced cytotoxic effects against human leukemia, pancreatic, cervical, and breast cancer cells. Another unique feature of naphthylisoquinoline alkaloids is their unprecedented biosynthetic origin from polyketidic precursors and not, as usual for isoquinoline alkaloids, from aromatic amino acids-a striking example of biosynthetic convergence in nature. Furthermore, remarkable botanical results are presented on the natural producers of naphthylisoquinoline alkaloids, the paleotropical Dioncophyllaceae and Ancistrocladaceae lianas, including first investigations on the chemoecological role of these plant metabolites and their storage and accumulation in particular plant organs.

The sarpagine-ajmaline type monoterpenoid indole alkaloids are among the most important groups of natural alkaloids, and the complex polycyclic and cage-like architectures present significant synthetic challenges. Because of their characteristic indole-fused azabicyclo[3.3.1]nonane structures and prominent biological activities, sarpagine-ajmaline related alkaloids have captured the attention of organic synthetic chemists for decades. In this chapter, the strategies employed in the synthesis of sarpagine-ajmaline related alkaloids are outlined, and the synthetic progress during the period of 2019-2023 is provided in detail. To provide potential targets for future synthetic endeavors, some sarpagine/ajmaline type alkaloids isolated in recent years with novel structures and biological activities are also summarized.

Indolactam alkaloids are a family of aromatic toxins produced by various actinobacteria and the cyanobacterium, Moorena producens. The best characterized examples include the teleocidins, lyngbyatoxins, olivoretins, blastmycetins, and pendolmycins, which share a nine-membered lactam core, comprised from l-tryptophanol and l-valine. Contact with indolactam alkaloids has been linked to severe dermatitis (swimmers itch), while accidental ingestion may lead to illness and fatalities. Indolactam alkaloids are also potent tumor promotors, due to their activation of protein kinase C isozymes. This chapter reviews the current literature on indolactam alkaloids, from their discovery in the early 1960s up to 2024. Topics covered include the isolation, structural elucidation, biosynthesis, bioactivity, and total synthesis of the indolactam alkaloid core.

Quinolizidine alkaloids isolated from various marine and terrestrial animals and plants are primarily composed of lupinine-, matrine-, and sparteine-type alkaloids. Matrine, phenanthroquinolizidines, bis-quinolizidines, and small molecules from amphibian skins are representative compounds of such alkaloids. Quinolizidine alkaloids harbor anticancer, antibacterial, antiinflammatory, antifibrosis, antiviral, and anti-arrhythmia. In this chapter, we comprehensively outline the biological activity and pharmacological action of quinolizidine alkaloids and discuss new avenues toward the discovery of novel and more efficient drugs based on these naturally occurring compounds. It is urgent for basic research and clinical practice to conduct more targeted comprehensive research based on the lead drugs of quinolizidine alkaloids with significant pharmacological activity.

The families of pyridoacridine, pyridoacridone, and pyrroloacridine alkaloids are fascinating classes of natural products that have attracted the attention of chemists for over 80 years. Since the first purification of a brightly colored molecule isolated from the sea anemone Calliactis parasitica in 1940, over 110 examples of these alkaloids have been reported from marine organisms. While the paucity of numbers of protons relative to carbons and nitrogens in these molecules presents challenges in structure solution, the chemist is rewarded by their bright pigmented colors and typically diverse biological activities. In the past, several authors have proposed biosynthetic relationships within the pyridoacridine family of alkaloids, formulating a family tree derived from the reaction of dopaminequinone and kynuramine to tie together over 75 alkaloids. Inclusion of two additional quinones, and one homologous diamine, building blocks, for which there is biomimetic synthesis support, is suggestive of a more expansive connected biogenesis that encompasses not only pyridoacridines, but also pyridoacridone, and pyrroloacridine alkaloids. This review covers the isolation, structure elucidation, and proposed biosynthesis and biogenesis of pyridoacridine, pyridoacridone and pyrroloacridine marine alkaloids published to the end of 2022. Biomimetic or bio-inspired syntheses of the compound classes are described and new biological activities reported since 2004 are updated.

This study involves aporphine alkaloids identified through ¹³C Nuclear Magnetic Resonance (NMR) spectroscopic data. For the present publication, articles were selected from several databases on aporphine alkaloids from 1994 to 2021. In this class, more than 700 compounds have been registered, with 221 were included in this section, among which 122 were characterized for the first time in the investigated period. The study also addresses their biosynthetic pathways, classifying substances according to their structural characteristics based on established literature. Furthermore, pharmacological activities related to the aporphine alkaloids highlighted in this section are also presented, giving an overview of the various applications of these compounds.

Morphinan alkaloids have attracted constant attention since the isolation of morphine by Sertürner in 1805. However, a group of 45 compounds possessing a complete ent-morphinan backbone can also be found in the literature. These compounds are related to the morphinandienone subgroup and display a substitution pattern which is different from the morphinans. In particular, these alkaloids could be substituted at position C-2 and C-8 either by a hydroxy function or a methoxy moiety. Four groups of ent-morphinan alkaloids can be proposed, the salutaridine, pallidine, cephasugine and erromangine series. Interestingly, the botanical distribution of the ent-morphinans is more widespread than for the morphinans and includes the Annonaceae, Berberidaceae, Euphorbiaceae, Fumariaceae, Hernandiaceae, Lauraceae, Menispermaceae, Monimiaceae, Papaveraceae, and Ranunculaceae families. To date, their exact mode of production remains elusive and their interplay with the biosynthetic pathway of other classes of benzyltetrahydroisoquinoline alkaloids, in particular aporphines, should be confirmed. Exploration of the biological and therapeutic potential of these compounds is limited to some areas, namely central nervous system (CNS), inflammation, cancer, malaria and viruses. Further studies should be conducted to identify the cellular/molecular targets in view of promoting these compounds as new scaffolds in medicinal chemistry.