ON THE FATE OF CATHARANTHINE AND VINDOLINE DURING THE PEROXIDASE-MEDIATED ENZYMATIC-SYNTHESIS OF ALPHA-3',4'-ANHYDROVINBLASTINE

The fate of catharanthine and vindoline during the peroxidase-mediated enzymatic synthesis of alpha-3',4'-anhydrovinblastine (AVLB) has been studied. The results showed that catharanthine and vindoline are suit able electron donors for the oxidizing intermediates of horseradish pe roxidase (compound I and compound II). The reduction of peroxidase com pound II is one of the limiting steps in the coupling reaction. In fac t, k(3) (compound II reduction constant) values were 2.53 X 10(3) M-1 S-1 and 3.57 X 10(3) M-1 S-1 for catharanthine and vindoline, respecti vely. These values are extremely low if we compare them with those fou nd for other substrates of peroxidase-catalyzed oxidations. From these results and the analysis of the reaction products in conditions in wh ich coupling occurred, we propose a mechanism where vindoline-free rad icals resulting from reaction of vindoline with the oxidized states of peroxidase are deactivated by reaction with catharanthine. Catharanth ine radicals actually set off the coupling reaction. (C) 1997 Elsevier Science Inc.