Synthesis and properties of vinyl carbamate epoxide, a possible ultimate electrophilic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate.
Vinyl carbamate reacted with dimethyldioxirane in dry acetone to give a high yield of pure crystalline vinyl carbamate epoxide. This epoxide was characterized by its NMR and MS spectra and elementary analysis. It is unstable at room temperature and has a half-life in water solution of approximately 32 minutes. It reacts with adenosine to form 1,N6-ethenoadenosine and more of this etheno nucleoside was found in hydrolysates of hepatic RNA of male mice injected i.p. with the epoxide than with vinyl carbamate. Tests with Salmonella typhimurium TA1535 showed that this epoxide is a strong direct mutagen. It is also more toxic in the mouse than vinyl carbamate. Studies on the carcinogenicity of this epoxide are in progress.
Park
K K
KK
McArdle Laboratory for Cancer Research, School of Medicine, University of Wisconsin, Madison 53706.
Surh
Y J
YJ
Stewart
B C
BC
Miller
J A
JA
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003461:Crystallography; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000633:toxicity; D004988:Ethers, Cyclic / Q000138:chemical synthesis / Q000633:toxicity; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens; D012486:Salmonella typhimurium / Q000187:drug effects; D014520:Urethane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D014867:Water
D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D009153:Mutagens; D014867:Water; D014520:Urethane; C017963:vinyl carbamate; C064746:vinyl carbamate epoxide