SYNTHESIS OF VINBLASTINE DERIVATIVES .6. SYNTHESIS OF 20'-DEETHYL-20'-DEOXY-C'-HOMOVINBLASTINE

Coupling of the acezinoindole derivative 1a with N,N-dimethyl-m-anisidine via the corresponding chloroindolenine results, after cyclization, in the formation of an 1:1 mixture of the homocleavamine derivatives 3I and 3II. The corresponding reaction of the homocleavamine derivative 4. with N,N-dimethyl-m-anisidine leads exclusively to compound 31 with unnatural configuration on C-10. By coupling of the diastereomeric lactams 5 with N,N-dimethyl-m-anisidine, the arylated lactams 6aI and 6aII are obtained. The hydrolysis of lactam 6aII followed by cycilzation results in the formation of homocleavamine 3II.- The coupling of the azecinoindole derivative 1b with vindoline via the chloroindolenine leads after cyclization to a mixture of the dimers 8I - 8IV in 85% yield. 20'-Deethyl-20'-deoxy-C'-homovinblastine 8II was isolated in 27% yield after repeated chromatography and its absolute stereochemistry determined by comparing its CD spectrum with those of other vinblastine derivatives. © 1990.