Spiropiperidine alkaloids

Spiropiperidine Alkaloids.— Two more total syntheses of perhydrohistrionico-toxin (39) have been reported,  

Hanaoka, N. Ogawa, K. Shimizu, and Y. Arata, Chem. and Pharm. Bull. (Japan), 1975, 23,1573. M. Onda, Y. Konda, Y. Narimatsu, H. Tanaka, J. Awaya, and S. Omura, Chem. and Pharm. Bull. (Japan), 1975, 23, 2462. 

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Further examples of the endocychc nitrone route to spirocychc adducts are the total syntheses of (—)-histrionicotoxin (230) by Holmes and of cyhndricines by Weinreb. Histrionicotoxin is one of many spiropiperidine alkaloids isolated from the poison-arrow frog Dendrobates histrionicus and has been the subject of many attempted total syntheses by a nitrone cycloaddition strategy that failed to provide the desired regioisomer, possibly through unfavorable steric interactions (265-268). Unlike these reports, Holmes and co-workers (101) found that the intermolecular reaction of nitrone (231), prepared by the 1,3-APT of the corresponding alkynyl-hydroxylamine carrying Oppolzer s chiral sultam auxiliary, afforded the styrene... 

Spiropiperidine Alkaloids.—Full details of a preliminarily reported synthesis of ( )-perhydrohistrionicotoxin (25) have been provided.24... 

Spiropiperidine Alkaloids.—The spirocyclic keto-base (18), which possesses a histrionicotoxin skeleton, undergoes an acid-catalysed retro-Mannich reaction, followed by re-condensation, to afford the unsaturated imine (19), with a pumiliotoxin skeleton. A mechanism for the transformation has been proposed.29... 

Histrionicotoxin, one of the spiropiperidine alkaloids from the skin of the Colombian frog Dendrobates histrionicus, containing two c/s-but-3-en-l-yne groups, is the first acetylenic alkaloid and also the first acetylene of animal origin. (The acid 12, present in the secretion of the soldier beetle, ChauHognatus lecontei. ... 

Spiropiperidine Alkaloids.—new synthetic pathway to ( )-perhydro-histrionicotoxin (27) (Scheme 5) has been elaborated. The final product is the intermediate (28), convertible to (27) as described earlier. A further synthetic entry into this ring system uses a Mannich-type spiro cyclization as key step and leads ultimately to racemic 2,7-epiperhydrohistrionicotoxin (29) (Scheme 6). The structure and stereochemistry of the urethane intermediate (30) were ascertained by X-ray diffraction analysis. ... 

Details of the X-ray crystallographic determination of the structure of dihydro-isohistrionicotoxin (17), a unique spiropiperidine alkaloid from the Colombian frog Dendrobates histrionicus, have appeared. 

Spiropiperidine Alkaloids.—Full experimental details of a preliminary reported total synthesis of racemic perhydrohistrionicotoxin have been published. ... 

Histrionicotoxins. Another poison frog, Dendrobates histrionicus occurred sympatric with the poison-dart frog Phyllobates aurotaenia in Western Colombia. Preliminary studies based primarily on mass spectrometry of compounds isolated by thin-layer chromatography, indicated the presence of another class of relatively simple alkaloids in extracts from a few specimens of this species. Three major alkaloids were later isolated from skin extracts of a population of Dendrobates histrionicus from southwestern Colombia and the structures of two of these were reported in 1971 (81). The compounds were unique spiropiperidine alkaloids with remarkable acetylenic and allenic centers of unsaturation in the side chain substituents. The parent compound was named histrionicotoxin after the specific name of the frog Dendrobates histrionicus from which it was first isolated. A number of histrionicotoxins were subsequently isolated and structurally defined 86, 253). Like pumiliotoxin C, the histrionicotoxins exhibit relatively low toxicity to mammals. 

The hydrochloride salt of histrionicotoxin was crystallized twice from methanol-acetone and then from isopropanol the hydrobromide salt of histrionicotoxin from isopropanol and the hydrochloride salt of dihydroisohistrionicotoxin from isopropanol-acetone. X-ray crystallographic analyses revealed the structures and absolute configurations of histrionicotoxin, [2R,6R,7S,8S]-7-(l-cis-buten-3-ynyl)-2-(cis-2-penten-4-ynyl)-l-aza-spiro-[5.5]-undecan-8-ol, and dihydroisohistrionicotoxin (81, 151, Fig. 9). These compounds were unusual spiropiperidine alkaloids with acetylene and/or allenic moieties in the side chains. 

Tokuyama, T., K. Uenoyama, G. Brown, J. W. Daly, and B. Witkop Allenic and acetylenic spiropiperidine alkaloids from the neotropical frog, Dendrobates histrionicus, Helv. Chim. Acta 57, 2597—2604 (1974). 

A retro-l,3-dipolar cycloaddition followed by an 1,3-dipolar cycloaddition was used for a highly efficient total synthesis of (-)-histrionicotoxin (4-354) (HTX) by Holmes and coworkers [123]. HTX is a spiropiperidine-containing alkaloid which was isolated by Doly, Witkop and coworkers [124] from the brightly colored poison-arrow frog Dendrobates histrionicus. It is of great pharmacological interest as a noncompetitive inhibitor of acetylcholine receptors. 

Nitramine and isonitramine alkaloids of Nitraria spp., previously described as decahydroquinolines, are now considered to be the epimeric spiropiperidines (104 and (105) respectively (A.A. Ibragimov et al, Khim.prirod. Soedin., 1981, 623 Z. Osmanov et al, ibid, 1982, 126),... 

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