Poisoned arrows

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... 

Strychnine was used in its impure powder form centuries before it was isolated. The nuts that yielded the seeds were given names such as poison nut or vomit nuts. Natives prepared poison arrows using the seeds and excretions of Strychnos species, and Europeans... 

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... 

Chemical warfare began in prehistoric times with the use of such weapons as poisoned arrows. Later, during the siege of Athens in about 400 BC, the Athenians were attacked by the Spartans with irritating sulfur dioxide, produced by burning sulfur with pitch upwind of the city. 

The use of toxic chemicals against humankind is as old as any warfare conflict. The use of the poisoned arrow against man - not animal - can be considered as the beginning of chemical warfare and would be eharacterized as the intentional use of chemicals. 

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. ... 

Precautions Once prepared, false hellebore loses its effectiveness quickly when exposed to air and sunlight. Store it in a cool, dry place to retain its potency. False hellebore was once used to make poison arrows—keep this in mind and use extreme caution when working with hellebore it is highly toxic if ingested. 

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. 

Mayor A (2003) Greek Fire, Poison Arrows and Scorpion Bombs Biological and Chemical Warfare in the Ancient World. New York Overlook Press. 

Greek mythology is littered with toxic tales. One of the many examples is Achilles humiliating death toward the end of the Trojan War. Paris let loose a poison arrow which lodged in his heel, the one vulnerable spot on his body. Poison arrows were used extensively by Odysseus and other warriors in the Homeric cycle and legends penned by other classical Greek authors and playwrights. 

In China, arrow poisons have been known to the Han and other peoples for at least 2500 years. They were used for both hunting and warfare, and documentary evidence indicates that the principal source of poison was Aconitum, the tubers of which yield aconitine. The same poison was also used in ancient India, where it was called visha and derived from a plant known as Bish. The hymns of the Rg Veda and Atharva Veda (1200-900 bc) show that poisoned arrows were used in war, and that the tubers of Aconitum were the major poison source. Later Buddhist and Sanskrit writings indicate the continued use of poisoned arrows and reveal that a second source of poison was decomposing snakes. 

Malawi neutralizes the arrow wound in flesh of animal killed by poisoned arrow, before meat is eaten (5, 10)... 

Curare was first identified when Spanish soldiers in South America found themselves the unwilling victims of poisoned arrows. It was discovered that the Indians were putting a poison on to the tips of their arrows. This poison was a crude, dried extract from a plant called Chondrodendron tomentosum and caused paralysis as well as stopping the heart. We now know that curare is a mixture of compounds. The active principle, however, is an antagonist of acetylcholine which blocks nerve transmissions from nerve to muscle. 

One of the earliest examples of chemical warfare was in the late Stone Age (10,000 BCE). Hunters known as the San, in southern Africa, used poison arrows. They dipped the wood, bone, and stone tips of their arrows in poisons obtained from scorpion and snake venoms, as well as poisonous plants (CBW Info, 2005 Tagate, 2006 Wikipedia, 2007a). 

Plant extract used by South American Indians to prepare poison arrows. Sold with different names (e.g. Tube-curare) depending on the container used for packaging. Toxicologically active principle is the alkaloid tubocurarine chloride. Muscle relaxant, toxic by respiratory paralysis and hypotension competitive blocker ACh receptor in muscle. 

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