The first 23-step total synthesis of the cyclodepsipeptide dolastatin 16 (1) has been
achieved. Synthesis of the dolaphenvaline and dolamethylleuine amino acid units using
simplified methods improved the overall efficiency. The formation of the 25-membered
macrocycle employing lactonization with 2-methyl-6-nitrobenzoic anhydride completed a
key step in the synthesis. Regrettably, the synthetic dolastatin 16 (1), while otherwise
identical (by X-ray crystal structure and spectral analyses) with the natural product, did not …