Svec RL,
Hergenrother PJ.
* University of Illinois at Urbana-Champaign, USA
Imidazotetrazines as Weighable Diazomethane Surrogates for Esterifications and Cyclopropanations.
Angew. Chem. Int. Ed. 2020;
59: 1857-1862
Key words
methylation - temozolomide - diazomethane surrogates
Significance
The reagent diazomethane is employed in the formation of methyl esters, as well as
for cyclopropanation reactions; however, it poses a severe risk of explosion and inhalation
toxicity. In the search for alternative reagents, the authors identify the cancer
chemotherapy drug temozolomide (TMZ), which is designed to methylate DNA in cancer
cells.
Comment
TMZ is a weighable solid, non-explosive and not acutely toxic. Upon hydrolysis and
release of methyl diazonium, TMZ methylates a broad range of carboxylic acids. Notably,
the protecting groups THP and MOM are stable to the reaction conditions. Furthermore,
catalysis with Fe(TPP)Cl enables the cyclopropanation of several styrenes.
