6957-05-7Relevant articles and documents
Oxidative metabolism of 1-(2-chloroethyl)-3-alkyl-3-(methylcarbamoyl)triazenes: Formation of chloroacetaldehyde and relevance to biological activity
Rouzer, Carol A.,Sabourin, Michelle,Skinner, Tricia L.,Thompson, Erin J.,Wood, Thomas O.,Chmurny, Gwendolyn N.,Klose, John R.,Roman, John M.,Smith Jr., Richard H.,Michejda, Christopher J.
, p. 172 - 178 (1996)
(Methylcarbamoyl)triazenes have been shown to be effective cancer chemotherapeutic agents in a number of biological systems. Because of their chemical stability, it is likely that their activity in vivo is the result of a metabolic activation process. Previous studies have shown that 1-(2-chloroethyl)-3-methyl-3-(methylcarbamoyl)triazene (CMM) and 1-(2-chloroethyl)-3-benzyl-3-(methylcarbamoyl)triazene (CBzM) are metabolized by rat liver microsomes in the presence of NADPH to yield the ((hydroxymethyl)carbamoyl)triazene analogs of the parent compounds. The present studies show that both compounds are also oxidized at the chloroethyl substituent to yield chloroacetaldehyde and a substituted urea. In the case of CBzM metabolism, 47% of the metabolized parent compound was recovered as benzylmethylurea, 8% was recovered as benzylurea, and 26% was recovered as the ((hydroxymethyl)carbamoyl)-triazene and carbamoyltriazene metabolites. These results suggest that the chloroethyl group is the favored initial site of metabolism. In reaction mixtures containing intitial concentrations of 300 μM. CBzM, 78 μM chloroacetaldehyde was produced, as compared to 58 μM chloroacetaldehyde produced from the metabolism of 300 μM CMM. The formation of chloroacetaldehyde, a known mutagenic DNA alkylating agent, may explain the biological activity of these compounds.
Formamides as Isocyanate Surrogates: A Mechanistically Driven Approach to the Development of Atom-Efficient, Selective Catalytic Syntheses of Ureas, Carbamates, and Heterocycles
Bruffaerts, Jeffrey,Von Wolff, Niklas,Diskin-Posner, Yael,Ben-David, Yehoshoa,Milstein, David
supporting information, p. 16486 - 16493 (2019/10/14)
Despite the hazardous nature of isocyanates, they remain key building blocks in bulk and fine chemical synthesis. By surrogating them with less potent and readily available formamide precursors, we herein demonstrate an alternative, mechanistic approach to selectively access a broad range of ureas, carbamates, and heterocycles via ruthenium-based pincer complex catalyzed acceptorless dehydrogenative coupling reactions. The design of these highly atom-efficient procedures was driven by the identification and characterization of the relevant organometallic complexes, uniquely exhibiting the trapping of an isocyanate intermediate. Density functional theory (DFT) calculations further contributed to shed light on the remarkably orchestrated chain of catalytic events, involving metal-ligand cooperation.
Bromodimethylsulfonium bromide (BDMS)-mediated Lossen rearrangement: Synthesis of unsymmetrical ureas
Yadav, Deepak K.,Yadav, Arvind K.,Srivastava, Vishnu P.,Watal, Geeta,Yadav, Lal Dhar S.
experimental part, p. 2890 - 2893 (2012/07/27)
Bromodimethylsulfonium bromide (BDMS) was found to be a very efficient reagent for Lossen rearrangement of hydroxamic acids to the corresponding isocyanates which were subsequently trapped in situ with various amines to afford unsymmetrical ureas in good to excellent yields (64-89%). The protocol is experimentally simple, mild, and represents valuable alternative to the existing methods for in situ activation of hydroxamic acids promoting Lossen rearrangement.
