ABSTRACT
Despite benzyne has been known since 1940, this fascinating species has received much attention only over the last decades. The renaissance of interest in aryne chemistry is ascribable to the seminal discovery that arynes can be generated in situ from stable and commercially available precursors under mild and neutral conditions. Thanks to their high reactivity, arynes are key intermediates in countless chemical transformations ranging from cycloadditions to insertions and, among all these approaches, multicomponent reactions (MCRs) are currently standing out in this field. In particular, this short article is focused on MCRs involving the concomitant use of benzyne and isocyanides. Furthermore, the first overview on aryne MCRs triggered by α-isocyanoacetamides is presented.
Subject(s)
Benzene Derivatives/chemistry , Chemistry Techniques, Synthetic/methods , Cyanides/chemistry , Benzene Derivatives/history , Chemistry Techniques, Synthetic/history , Cyanides/history , History, 20th Century , History, 21st Century , Molecular StructureSubject(s)
Glutathione Peroxidase/chemistry , Liver/enzymology , Selenium/history , Animals , Benzene Derivatives/chemistry , Benzene Derivatives/history , Cell Fractionation/history , Glutathione Peroxidase/isolation & purification , History, 20th Century , Male , Rats , Rats, Sprague-Dawley , Selenium/deficiency , Substrate SpecificityABSTRACT
Benzene-induced cancer in humans was first reported in the late 1920s. Carcinogenesis findings in animals were not reported conclusively until 1979. Industry exploited this "discrepancy" to discredit the use of animal bioassays as surrogates for human exposure experience. The cardinal reason for the delay between first recognizing leukemia in humans and sought-after neoplasia in animals centers on poor design and conduct of experimental studies. The first evidence of carcinogenicity in animals manifested as malignant tumors of the zymbal glands (sebaceous glands in the ear canal) of rats, and industry attempted to discount this as being irrelevant to humans, as this organ is vestigial and not present per se in humans. Nonetheless, shortly thereafter benzene was shown to be carcinogenic to multiple organ sites in both sexes of multiple strains and multiple species of laboratory animals exposed via various routes. This paper presents a condensed history of the benzene bioassay story with mention of benzene-associated human cancers.
