Frogs, poison-arrow

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. 

The Beckmann rearrangement was used as a key step (41% yield, under standard conditions) for the synthesis of the natural alkaloid Pumiliotoxin C 359, which was originally isolated from the skin extracts of Dendrobates pumilio (a strikingly coloured Panamanian poison arrow frog) (equation 139). ( )-Pumiliotoxin C was also synthesized by a similar ring formation process by Mehta and Praveen. ... 

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... 

The Dendrobatid poison arrow frogs of Central and South America exude a potent mixture of alkaloids from their skins. It was originally thought that the frogs biosynthesized these alkaloids, but it has since been shown that they are of dietary origin. The skin exudate of the Colombian frog Minyobates bombetes causes severe locomotor difficulties, muscle spasms and convulsions upon injection in mice. The major component of the alkaloid mixture is 251F3. Jeff Aube of the University of Kansas recently described (J. Am. Chem. Soc. 2004,126,5475) the enantioselective total synthesis of 3. The key step in the synthesis was the cyclization of the keto azide 2. 

Some animals also contain toxic steroids. Batra-chotoxin of the Columbian poison arrow frog (Fig. 22-12) is present in amounts of only 50 pg per frog.329 330... 

Batrachotoxin (459), the steroidal alkaloid from the poison arrow frog Phyllo-bates aurotaenia, continues to engage the attention of chemists and pharmacologists. This substance exerts novel, selective effects on electrogenic membranes. In many cases this activity can be explained in terms of an irreversible increase in permeability to sodium ions. The subsequent reactions promoted by (459) can be blocked reversibly by tetrodotoxin. ... 

A unique class of steroidal alkaloids, the batrachotoxinins, is isolated in small quantities from the skins of poison arrow frogs and also from the feather of a New Guinea bird. One of the key steps during the total synthesis of (+)-batrachotoxinin A by Y. Kishi et al. was a Michael addition to form a seven-membered oxazapane ring. The removal of the primary TBS protecting group was achieved by treatment with TASF and the resulting alkoxide attacked the enone at the 3-position to afford an enolate as the Michael adduct. The enolate was trapped with phenyl triflimide as the end triflate. 

The synthesis of batrachotoxin (439), the steroidal alkaloid from the poison arrow frog Phyllobates aurotaenia, has continued to attract attention. The partial synthesis of various 3) -methoxy-3a,9a-oxido-7a-hydroxy-lla-acetoxy-5/ -steroids has been reported. In particular (Scheme 24), the -double bond... 

Malassene and co-workers recently examined the application of the Thorpe-Ziegler cyclization for synthesis of perhydrohistrionicotoxin, a skin extract of the Colombian poison arrow frog, Dendrobates histrionicus. Under standard conditions, dinitrile 37 was directly converted into spiropiperidine 38 through the Thorpe-Ziegler cyclization, completing construction of the carbon framework of perhydrohistrionicotoxin. 

Turning to the subject of many an adventure story, ichthyothereol is the active ingredient of a poisonous substance used in arrowheads by the Indians of the Lower Amazon River Basin. It causes convulsions in mammals. And histrionicotoxin is isolated from the skin of poison arrow frog, a highly colorful species of the genus Dendrobates. The frog secretes this compound and similar ones as defensive venoms and mucosal-tissue irritants against both mammals and reptiles. 

SiLVERSTONE, P. A. A revision of the poison-arrow frogs of the genus Dendrobates Wagler. Natural History Museum of Los Angeles County, Science Bulletin 21, 1—55... 

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