Indolizidines isolation

The alkaloid 249H, Fig. (11), was isolated from the skin extracts of the poisonous frog Dendrobates auratus of the Isla Taboga of the Pacific coast of Panama [26]. A sample containing only traces of impurities was obtained by successive column chromatography of the methanolic skin extract. H and C NMR spectroscopy and correlation spectra were only consistent with a branched substituent, the first to be reported for simple indolizidines isolated from frog skin, and an unusual cw-fused trisubstituted indolizidine nucleus. 

An efficient kinetic resolution was also observed during the (—)-sparteine-mediated deprotonation of the piperidin-2-yhnethyl carbamate rac-112 (equation 25). By treatment of rac-112 with s-BuLi/(—)-sparteine (11), the pro-S proton in (/ )-112 is removed preferentially to form the lithium compound 113, which undergoes intramolecular cyclo-carbolithiation, and the indolizidinyl-benzyllithium intermediate 114 was trapped with several electrophiles. The mismatched combination in the deprotonation of (5 )-112, leading to cp/-113, does not significantly contribute to product formation. Under optimized conditions [0.75 equivalents of s-BuLi, 0.8 equivalents of (—)-sparteine, 22 h at —78°C in diethyl ether] the indolizidine 115 was isolated with 34% yield (based on rac-112), d.r. = 98 2, e.r. = 97 3 optically active (5 )-112 was recovered (46%, 63% ee). 

Moreover, it is known that toads belonging to the genus Melanophryniscus contain toxic alkaloids in their skin °°. From Melanophryniscus montevidensis, alkaloids of the pumiliotoxin (PTX) group and indolizidines were isolated. 

These authors also showed that the indolizidine skeleton can be prepared from cyclopropyl dipolarophiles (Scheme 1.16). The cycloaddition of alkyhdenecyclo-propanes 67 with various nitrones (e.g., 68) afforded the expected isoxazolidine adducts 69 and 70, commonly forming the C(5) substituted adducts 70 (97,105-108) predominantly but not exclusively (109-111). Thermally induced rearrangement of the spirocyclopropyl isoxazolidine adduct 70 afforded the piperidinones 71 (107,108). These authors propose reaction via initial N—O bond homolysis of 70 to diradical 72 followed by ring expansion through relief of the cyclopropyl ring strain forming the carbonyl of a second diradical intermediate 73, which cyclizes to afford the isolated piperidinone 71. 

Pandey and Lakshmaiah (10) further extended their methodology to the construction of the indolizidine and pyrrolizidine bicyclic skeleta. The basic precursor 41, which was realized in three straightforward steps, underwent double desilyation and subsequent cycloaddition with ethyl acrylate to furnish the two regioisomers 42 and 43 in essentially quantitative yield and in a 17 3 ratio. The major regioisomer was isolated in a 7 3 endo/exo ratio. Further elaboration of the major products where (n=l) and (n = 2) delivered the natural products... 

Stellettamide A and B, Fig. (27), indolizidine alkaloids isolated from sponges of the genus Stellettci have been reported as inhibitors of... 

The 5,8-disubstituted indolizidines and 1,4-disubstituted quinolizidines are the more common structural patterns found in amphibian skin[21]. None of these alkaloids has so far been reported from any other source. In addition, the biological activity of only a few 5,8-disubstituted indolizidines has been investigated due to the isolation in minute quantities from the skin. Among them, the relative stereochemistry of quinolizidine 2071 was anticipated to be 75 by our chiral synthesis of 76[35] followed by stereocontrolled synthesis of 75[36]. A sample of synthetic racemate of 75 had produced the best separations on GC analysis with (3-dextrin chiral column[36]. 

Glycosidase-inhibiting alkaloids from plants are classified into five structural classes polyhydroxylated pyrrolidines, piperidines, indolizidines, pyrrolizidines, and nortropanes. Furthermore, they also occur as the glycosides. This review describes recent studies on isolation, characterization, glycosidase inhibitory activity, and therapeutic application of the sugar-mimicking alkaloids from plants. 

Benzindolizidine systems 963 are generated in moderate yields by a hexabutylditin-mediated consecutive radical addition, cyclization, and oxidation process from easily accessible l-(2-iodoethyl)indoles 962 and methyl acrylate, in one step (Scheme 186) <2000TL10181>. l-(2-Iodoethyl)-l//-pyrrole-2-carbaldehyde was also subjected to the tandem radical addition-cyclization process, and the indolizidine derivative 964 was isolated in modest yield as the major product together with a small amount of starting material (Equation 229). 

The isolation of indolizidine 207A in sufficient quantity for nuclear magnetic resonance spectroscopy (87) established a 5-(pent-4-enyl)-8-methylindolizidine structure as shown in IX. The (5R,8R,9S) absolute configuration shown is the same as that of 205A, which contains a terminal... 

Only a few compounds of these classes of alkaloids have been reported from marine organisms. Clavepictine B (107), which was isolated from the ascidian Clavelinapicta, is marginally cytotoxic. Stellettamine A (108), which is an indolizidine derivative from a sponge Stelletta sp., is antifungal and cytotoxic. It... 

Indolizidine and quinolizidine alkaloids have been found in different natural sources and have been isolated from amphibians, ants, fungi, marine organisms and plants. Most of them have noxious or toxic properties and... 

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