Mass spectral studies of diamide compounds obtained by the Ugi reaction

G.F. RETA; F.M. CECATI; N.A. TERUEL; P.C. ROSSOMANDO; O.J. DONADEL; V.S. MARTÍN; C.E. TONN; M. KURINA-SANZ; C.E. ARDANAZ

RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM.

JOHN WILEY & SONS LTD

Año: 2013 vol. 27 p. 2033 - 2038

0951-4198

The Ugi multicomponent reaction[1] involves the combination of an amine, an acid, a carbonyl compound and an isocyanide to produce a diamide. Several diamides obtained by this methodology have shown cytotoxic effects.[2,3] In order to evaluate their cellularmetabolism in in vitro assays it is necessary to develop techniques that allow the unambiguous identification of these compounds and their metabolites. Most classical methods lack the minimal required sensitivity since the expected concentrations in both culturemedia and intracellular environments are very low (around 10?6 M). The present work reports the synthesis of the two cinnamic acid-derived diamides N-(1-(tert-butylamino)-2-methyl-1-oxopropan-2-yl)- N-phenethylcinnamamide (1) and N-(1-(tert-butylamino)-2- methyl-1-oxopropan-2-yl)-N-phenylcinnamamide (2) by a "one-step-one-pot" procedure (Fig. 1), as well as the study of their fragmentation pathways by mass spectrometry. The characterization of certain fragment ions could be a tool for the detection of these compounds and their derived metabolites in complex biological matrices.