Synthesis of Chondramide A Analogues with Modified b-Tyrosine and Their Biological Evaluation

Cyclodepsipeptides comprise a unique class of secondary metabolides. They frequently contain unusual amino acids, like d-amino acids or N-methylated amino acids and hydroxy acids that typically originate from the polyketide pathway. Incorporation of the hydroxy acid results in an ester bond, explaining the term “depsi”. Many cyclodepsipeptides have been isolated from marine sponges and found to display interesting biological activities. Thus, cyclodepsipeptides with anti-HIV or anti-tumor activity are known. With the peptide subunit cyclodepsipeptides are clearly protein-like and therefore it is not surprising that they very often modulate protein–protein interactions. Very prominent examples of such cyclodepsipeptides, displaying anti-tumor activity are the jasplakinolides and the chondramides. Jasplakinolide (1) was isolated from the marine sponge Jaspis splendans many years ago (Figure 1).