Hydrogen cyanide drugs

The apparently quite broad structural requirements for anticonvulsant activity, noted earlier in this chapter, extend to yet another class of five-membered heterocycles that include an imide function. Imidazo-2,4-diones, better known as hydan-toins, have comprised some of the most widely used drugs for treating severe motor and psychomotor epileptic seizures. The general reaction used to prepare this heterocyclic system involves the treatment of a carbonyl compound with ammonium carbonate and potassium cyanide. The first step in the complex sequence can be visualized as the addition of the elements of ammonia and hydrogen cyanide to give an a-aminonitrile (88-2). Addition of ammonia to the cyano group would then lead to an amidine (88-3). Carbon dioxide or carbonate ion present in the reaction... 

Pests, once estabUshed, are extremely difficult to eradicate and prevention is easier and less expensive than the total sacrifice of the contaminated product. Apart from the commonsense hygiene precautions, many commercial firms use a variety of techniques to eradicate insects in stored crude drugs. None of the methods presently available are ideal dry or moist heat may damage the constituents fumigation with hydrogen cyanide or methylbromide may cause toxicity, while the commonly used ethylene oxide has been banned by the EU because of the suspected carcinogenicity of the chlorohydrin formed from the gas. Some companies use irradiation. Many studies have been conducted on the effects of this controversial method on the constituents of medicinal plants. Most reported studies show no effect on chemical content, with the exception of opium where... 

The addition of hydrogen cyanide to benzaldehyde forms a compound called mandelonitrile. (Rj-Mandelonitrile is formed from the hydrolysis of amygdalin, a compound found in the pits of peaches and apricots. Amygdalin is the principal constituent of laetrile, a compound that was once highly touted as a treatment for cancer. The drug was subsequently found to be ineffective. Is (R)-mandelonitrile formed by attack of cyanide ion on the Re face or the Si face of benzaldehyde ... 

Most powerful poisons are lethal because they inhibit enzymes required for life. Hydrogen cyanide and hydrogen sulfide liberate ions, CN" and HS . that combine with ferric iron atoms in the cytochromes, which are heme enzymes that catalyze the cellular oxidation reactions required for life. Many drugs are enzyme inhibitors. 

For more examples of synthetic approaches that have reduced the use of ammonia, see also the case studies describing catalytic dehydrogenation of diethanolamine, HCN-free synthesis of the amino acids, and HCN-free synthesis of the specialty chemical, sarcosinate, all listed under the section on hydrogen cyanide, and the case study describing synthesis of the drug aprepitant. 

Incidentally, the oxidation of reduced cytochrome is prevented by cyanide, and it is this that accounts for the poisonous effects of cyanide in the body. If cytochromes cannot be oxidized, hydrogen transport cannot occur and ATP cannot be made. The result is a quick death through energy-lack. Some narcotic drugs, on the other hand, work by slowing down the rate at which oxidized... 

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