Total synthesis and configurational assignment of chondramide A.

The first total synthesis of the cyclodepsipeptide chondramide A (2 b) is described. This depsipeptide is composed of four subunits, namely L-alanine, N-Me-D-tryptophan, 3-amino-2-methoxy-propionic acid (beta-tyrosine derivative), and a 7-hydroxy-alkenoic acid. While the configuration of the stereogenic centers in the 7-hydroxy-alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2S,3R) or (2L,3L), respectively. The synthesis of the 3-amino-2-methoxy-3-arylpropanoic ester 20 b relied on an asymmetric dihydroxylation yielding diol ent-15 a followed by a regioselective Mitsunobu substitution leading to 3-azido-2-hydroxypropanoate 18 b. We could also show that the ester bond in the seco compound 26 b can be fashioned by a Mitsunobu esterification by using hydroxy ester (7S)-7 and the tripeptide acid 25 b. This synthesis should allow for the preparation of various analogues.