SYNTHESIS OF DOLASTATIN-10 AND [R-DOE]-DOLASTATIN-10

A stepwise synthesis of dolastatin 10 starting from the dolaphenine re sidue is described. The chiral dola isoleuine and dolaproine residues were obtained by 5-step procedures from the corresponding N-Boc amino acid. The key steps are respectively the NaBH4 reduction of an allylic ketone and the addition of an achiral Z-crotylboronate on the N-Boc-L -prolinal. Peptidic couplings were efficiently realised with reagents developed in the laboratory.