in angina pectoris and myocardial infarction despite its poor and variable absorption. The positive properties of ouabain regarding the prophylaxis and treatment of these two indications are documented by several studies. Animal use of ouabain The African crested rat (Lophiomys imhausi) has a broad, white-bordered strip of hairs covering an area of glandular skin on the flank. When the animal is threatened or excited, the mane on its back erects and this flank strip parts, exposing the glandular area. The hairs in this flank area are highly specialised; at the tips they are like ordinary hairs, but are otherwise spongy, fibrous, and absorbent. The rat is known to deliberately chew the roots and bark of the Poison-arrow tree (Acokanthera schimperi), which contains ouabain. After the rat has chewed the tree, instead of swallowing the poison it slathers the resulting masticate onto its specialised flank hairs which are adapted to absorb the poisonous mixture. It thereby creates a defense mechanism that can sicken or even kill predators which attempt to bite it. Synthesis The total synthesis of ouabain was achieved in 2008 by Deslongchamps laboratory in Canada. It was synthesized under the hypothesis that a polyanionic cyclization (double Michael addition followed by aldol condensation) would allow access to a tetracyclic intermediate with the desired functionality. The figure below shows the key steps in the synthesis of ouabain. In their synthesis, Zhang et al. from the Deslongchamps laboratory condensed cyclohexenone A with Nazarov substitute B in a double Michael addition to produce tricycle C. At the indicated position, C was reduced to the aldehyde and the alcohol group was protected with p-methoxybenzyl ether (PMB) to form the aldol precursor needed to produce D. After several steps, intermediate E was produced. E contained all the required functionalities and stereochemistry needed to produce ouabain. The structure of E was confirmed by comparison against the degradation product of ouabain. Methylation of E, catalyzed by rhodium, produced F. The dehydroxylation and selective oxidation of the secondary hydroxy group of F produced G. G reacted with triphenyl phosphoranylidene ketene and the ester bonds in G were hydrolyzed to produce ouabagenin, a precursor to ouabain. The glycosylation of ouabagenin with rhamnose produced ouabain. History Africa Poisons derived from Acokanthera plants are known to have been used in Africa as far back as the 3rd century BC when Theophrastus reported a toxic substance that the Ethiopians would smear on