Mitomycin antitumor compounds - Part 1. CD studies on their molecular structure

The UV-Vis and circular dichroism (CD) spectra of several mitomycin antitum or compounds and some of their derivatives were analyzed in order to attrib ute the proper assignment to their electronic transitions. The lowest energ y pi-->pi* transition was found to depend on the effect of the auxochromic group in the aromatic ring, whereas the three n-->pi* transitions, present at around 240, 400 and 560 nm, are related to the C(9)=O of the carbamoyl g roup and to the C(8)=O and the C(5)=O of the quinone, respectively. The chi rality of the C(9) is responsible for the sign of the Cotton effect (CE) at around 240 nm, whereas the substituents of the chromophore for mitosane de rivatives and the conformation of the carbamoyloxymethyl group at C(9) dete rmine the CE sign of the (1)A-->L-1(b) transition. When the aziridine ring was opened and mitosenes derivatives were obtained, CD spectra did not diff er significantly among the compounds and the bands associated to the differ ent transitions had similar Cotton effect. Our findings suggest that the di fferences in the CD spectra, observed between mitosanes and mitosenes, are probably related to the more rigid molecular structure of the mitosene deri vatives and the different conformations in solution of the C(9) side chain. (C) 2001 Elsevier Science B.V. All rights reserved.