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.
Schmauder
Anke
A
Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany.
Sibley
L David
LD
Maier
Martin E
ME
D000596:Amino Acids / Q000737:chemistry; D001386:Azides / Q000138:chemical synthesis* / Q000737:chemistry; D001426:Bacterial Proteins / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
C550821:3-azido-2-hydroxypropanoate; D000596:Amino Acids; D001386:Azides; D001426:Bacterial Proteins; D001688:Biological Products; D047630:Depsipeptides; D011422:Propionates; C097819:chondramide A