THE DOLASTATINS-16 - SYNTHESIS OF DOLAPHENINE

Synthesis of dolaphenine (2), the thiazole-containing unit of the stro ngly antineoplastic peptide dolastatin 10 (1), has been summarized. Wh ile conversion (4 --> 7 or 4 --> 11) of phenylalanine to thiazolidines (7) or thiazolines (11) was routinely uneventful, a dependable proced ure for dehydrogenation of these intermediates to dolaphenine (2, Doe) proved elusive. While several types of specially prepared manganese d ioxide were found most effective for the dehydrogenation, yields of do laphenine varied from almost nil to over 70%. Some of these reactions resulted in partial to complete racemization of the phenylalanine deri ved chiral carbon.