Stereochemistry of Kahalalide F

The stereochemistry of the amino acids in the marine-derived cyclic depsipeptide kahalalide F has been defined by a series of degradation reactions (hydrolysis, ozonolysis, Edman degradation, and Marfey derivatization), yielding smaller fragments of the marine natural product. The results from these reactions agree with the structure originally proposed by Hamann and Scheuer and with the same stereochemistry of most of the component amino acids more recently proposed by Goetz, Yoshida, and Scheuer. However, our assignments of d-Val(3) and l-Val(4) are the reverse of previous assignments made as l-Val(3) and d-Val(4). The present (reversed) stereochemistry is crucial for the antitumor activity of kahalalide F.