Eine neue synthese von vinblastin-derivaten II: Synthesekonzept und modelluntersuchungen

Abstract Starting from vindoline ( 2 ) and 7-methoxycarbonylazoninoindole derivatives 7 , a new concept for the synthesis of vinblastine 1a type alkaloids with natural C(16') stereochemistry is described. Using lactam 8 and chloroindolenine 9 as key intermediatea a stereocontrolled coupling between the dihydroindole and indole subunits under formation of 10 should be achieved. Methanolysis of 10 and intramolecular No-alkylation of the resulting 12a should lead to 20 - deethyl-20'-deoxyvinblastine 13a . Model investigations for the synthesis of lactam 8 are described. A new method for the introduction of the nitrile group into the α-position of 2-alkylindoles using α-hydroxyalkyl substituted derivatives as starting materials is presented.