Synthesis of Potential Prophylactic Agents against Cyanide Intoxication
Annual rept. 3 Sep 1991-3 Aug 1992
SOUTHERN RESEARCH INST BIRMINGHAM AL
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The goal of the proposed research is to identify through synthesis and testing compounds that may provide prophylaxis against cyanide intoxication. Our review of the literature for both cyanide prophylactics and antidotes suggested that the following strategies for sequestration of cyanide ion through covalent bond formation should be effective at preventing the toxic reaction thereto 1 administration of sulfur-rich compounds e.g., polysulfides and cysteine derivatives which could serve as sulfane sulfur donors to the principal cyanide detoxification enzyme system, rhodanese, and other sulfur transferases 2 administration of compounds containing multiple carbonyl moieties, such as analogs of pyruvate and alpha-ketoglutarate, which can bind cyanide through cyanohydrin formation and 3 exploration of additional classes of compounds which can directly react with cyanide, including i N-alkoxy and N-alkylthio heterocycles, and ii phthalocyanines and porphyrins, as well as similar compounds which can covalently eliminate cyanide. results are shaping our current synthetic program. During this report period we-prepared examples of all three compound types just described. The 57 new compounds prepared and submitted this period were distributed among these compound classes as follows sulfur-rich species, 34 polycarbonyl compounds, 14 alkyl- and alkoxy- substituted small nitrogenous heterocycles, 7 and phthalocyanines, 2. Some of these compounds, particularly among the nitrogenous heterocycles, contained ancillary functionality such as carbonyl, which could also neutralize cyanide. In addition to these novel compounds, samples of several materials were re- submitted because of decomposition of the original supply prior to testing, or because additional quantities were required.
- Organic Chemistry
- Chemical, Biological and Radiological Warfare