A NEW APPROACH TO SYNTHESIS OF VINBLASTINE ANALOGS - ADDITION OF ORGANOZINC REAGENTS TO THE DIHYDROPYRIDINIUM ION GENERATED BY FRAGMENTATIVE COUPLING OF CATHARANTHINE AND VINDOLINE
Rj. Sundberg et al., A NEW APPROACH TO SYNTHESIS OF VINBLASTINE ANALOGS - ADDITION OF ORGANOZINC REAGENTS TO THE DIHYDROPYRIDINIUM ION GENERATED BY FRAGMENTATIVE COUPLING OF CATHARANTHINE AND VINDOLINE, Bioorganic & medicinal chemistry letters, 4(16), 1994, pp. 1999-2004
The dihydropyridinium ion generated by Potier-Polonovski coupling of c
atharanthine and vindoline reacts with organozinc reagents to give eit
her 15' or 21'-substituted adducts. The former are unstable enamines b
ut 20'-deoxyvinblastine analogs can be isolated after NaBH4 reduction.
21'-Phenylanhydrovinblastine and the 15'-ethyl, 15'-tert-butyl and 15
'-phenyl analogs of 20'-deoxyvinblastine show activity in the micromol
ar range as tubulin assembly inhibitors.