Alkaloids: Chemistry and Biology最新文献

Rigidins (2-6) are pyrrolopyrimidine alkaloids isolated from marine tunicates. Since their isolation, refinement of their total syntheses, and biochemical evaluation, interest toward this pyrrolo[2,3-d]pyrimidine scaffold as a medicinal candidate has been triggered. The derivatization of these natural products has led to the discovery of a novel range of 7-deazahypoxanthines, which exhibit extremely potent anticancer activity in human cancer cell lines. A major breakthrough toward the synthesis of rigidin and various rigidin analogues has been the application of multicomponent reactions (MCRs). The rapid assembly of molecular diversity and flexibility displayed by MCRs makes it an attractive strategy for the preparation of rigidin-inspired small molecules. Furthermore, a number of rigidin-like 7-deazaxanthine compounds have been reported in the literature and the popularity of implementing MCRs to construct these 7-deazaxanthines is highlighted here. It is our hope that the synthetic methods described in this chapter will result in the further generation of rigidin-inspired compounds that will move on from being "hits" into "leads" in the medicinal chemistry drug discovery pipeline and potentially into anticancer therapeutics.

This chapter provides a comprehensive overview of recent achievements in the area of Galbulimima alkaloids. Following a discussion of the isolation of Galbulimima alkaloids and structural features of members of this fascinating family of secondary metabolites, biological properties of selected compounds are briefly discussed. Furthermore, the proposed biosynthetic routes toward Galbulimima alkaloids are outlined. The main section of the chapter is devoted to a detailed discussion and comparison of all total syntheses of Galbulimima alkaloids published to date.

There have been substantial developments in the chemistry and biology of the acridone alkaloids in the 16years since the topic was last reviewed in this series of monographs (2000). The present survey covers the literature from mid-1999 to 2016. A brief overview of the biosynthesis of acridone alkaloids is followed by details of the occurrence and characterization of known alkaloids from new sources, and of novel alkaloids. The classes covered include simple acridone alkaloids, C-prenylacridones, furo[3,2-b]- and furo[2,3-c]acridones, pyrano[3,2-b]- and pyrano[2,3-c]acridones, and dimeric alkaloids containing acridone moieties. Syntheses of acridone alkaloids and certain analogs reported during the review period are comprehensively covered. The final section summarizes aspects of their bioactivity, including cytotoxicity and anticancer activity, antimicrobial and antiparasitic properties, and enzyme inhibition. The chapter concludes with a brief description of important bioactive synthetic analogs.

This review focuses on the total synthesis of lundurines A-C. Their main structural feature is a unique cyclopropa[b]indole core that has been found only in these alkaloids. In addition to this characteristic structure, the biological activity makes them as attractive synthetic targets. However, almost two decades passed from their isolation and structural determination in 1995 to their first total synthesis. The first part of this review summarizes the synthetic approaches to the tri- and tetracyclic ring systems of lundurine as well as an inter- and intramolecular cyclopropanation strategy that gives the cyclopropa[b]indole core. The second part presents a detailed description of four total syntheses that were reported from 2014 to 2016. In addition, the asymmetric total synthesis of the related alkaloids grandilodine C and lapidilectine B is described.

The structurally related natural products (-)-homaline, (-)-hopromine, (-)-hoprominol, and (-)-hopromalinol have been collectively termed the homalium alkaloids. All four alkaloids possess bis-ζ-azalactam structures, but differ only by the identities of the side chain on each lactam ring. Since their isolation (from the leaves of Homalium pronyense Guillaum found in the forests of New Caledonia), there have been several syntheses of homaline, hopromine, hoprominol, and hopromalinol in both racemic and enantiopure forms. The most highly yielding and versatile strategy for their synthesis employs the conjugate addition of an enantiopure lithium amide reagent to an α,β-unsaturated ester as the key stereodefining step. This methodology has been used in the syntheses of all four members of the homalium alkaloid family and their stereoisomers.

This chapter presents an overview of the chemistry and pharmacology of the alkaloids found in species of the Annonaceae family. The occurrence of alkaloids from Annonaceae species, as well as their chemical structures and pharmacological activities are summarized in informative and easy-to-understand tables. Within the Annonaceae family, the genera Annona, Duguetia, and Guatteria have led to many important publications. Valuable and comprehensive information about the structure of these alkaloids is provided. The alkaloids of the aporphine type represent the predominant group in this family. Many of the isolated alkaloids exhibit unique structures. In addition to the chemical structures, the pharmacological activities of some alkaloids are also presented in this chapter. Thus, the leishmanicidal, antimicrobial, antitumor, cytotoxic, and antimalarial activities observed for these alkaloids are highlighted. The chapter is presented as a contribution for the scientific community, mainly to enable the search for alkaloids in species belonging to the Annonaceae family.

Securinega alkaloids represent a family of plant secondary metabolites known for 50 years. Securinine (1), the most abundant and studied alkaloid of this series was isolated by Russian researchers in 1956. In the following years, French and Japanese scientists reported other Securinega compounds and extensive work was done to elucidate their intriguing structures. The homogeneity of this family relies mainly on its tetracyclic chemical backbone, which features a butenolide moiety (cycle D) and an azabicyclo[3.2.1]octane ring system (rings B and C). Interestingly, after a period of latency of 20 years, the Securinega topic reemerged as a prolific source of new natural structures and to date more than 50 compounds have been identified and characterized. The oligomeric subgroup gathering dimeric, trimeric, and tetrameric units is of particular interest. The unprecedented structure of the Securinega alkaloids was the subject of extensive synthetic efforts culminating in several efficient and elegant total syntheses. The botanical distribution of these alkaloids seems limited to the Securinega, Flueggea, Margaritaria, and Breynia genera (Phyllanthaceae). However, only a limited number of plant species have been considered for their alkaloid contents, and additional phytochemical as well as genetic studies are needed. Concerning the biosynthesis, experiments carried out with radiolabelled aminoacids allowed to identify lysine and tyrosine as the precursors of the piperidine ring A and the CD rings of securinine (1), respectively. Besides, plausible biosynthetic pathways were proposed for virosaine A (38) and B (39), flueggine A (46), and also the different oligomers flueggenine A-D (48-51), fluevirosinine A (56), and flueggedine (20). The case of nirurine (45) and secu'amamine (37) remains elusive and additional studies seem necessary to understand their mode of production. The scope of biological of activities of the Securinega alkaloids was mainly centered on the CNS activity of securinine (1), although the exact mechanism of action remained in part unknown. Nevertheless, for its stimulant and antispasmodic effects securinine nitrate was marketed as a drug in the USSR until the early 1990s. Moreover, securinine (1) and several other Securinega alkaloids recently demonstrated promising anticancer properties. In particular securinine (1) demonstrated markedly benefits in the treatment of acute myeloid leukemia.

This survey on steroidal alkaloids of the Veratrum and Solanum family isolated between 1974 and 2014 includes 187 compounds and 197 references. New developments in the chemistry and biology of this family of natural products with a special focus on the medicinal relevance of the jervanine alkaloid cyclopamine are discussed.

This chapter is focused on madangamines, a small group of complex diamine alkaloids isolated from marine sponges of the order Haplosclerida, and covers their isolation, characterization, biogenesis, biological activity, and synthesis. Structurally, madangamines are pentacyclic alkaloids with an unprecedented skeletal type, characterized by a common diazatricyclic core and two peripheral macrocyclic rings. The isolation of these alkaloids from Xestospongia ingens (madangamines A-E) and Pachychalina alcaloidifera (madangamine F) is described in detail. Physical and complete spectroscopic 1H and 13C NMR data are included. The proposed biogenesis of madangamines from ammonia, a functionalized three-carbon unit, and saturated or unsaturated linear long-chain dialdehydes, via partially reduced bis-alkylpyridine macrocycles, is discussed. The synthesis of alkaloids of the madangamine group has been little explored, with only one total synthesis reported so far, that of (+)-madangamine D. This review also describes several model synthetic approaches to the diazatricyclic ABC core of these alkaloids, as well as model studies on the construction of the (Z,Z)-unsaturated 11-membered E macrocycle common to madangamines A-E, the 13- and 14-membered D rings of madangamines C-E, and the all-cis-triunsaturated 15-membered D ring of madangamine A. Some members of this group have shown significant in vitro cytotoxicity against a number of cancer cell lines.