165754-55-2Relevant articles and documents
Site-selective epimerization of a fungal cyclodepsipeptide via a 5- aminooxazole intermediate
Oberhauser, Berndt,Baumann, Karl,Grohmann, Brigitte,Sperner, Hildegard
, p. 893 - 896 (1999)
The epimerization of the cyclic depsiheptapeptide 1 at a single amino acid (Leu) was achieved in four steps. After regio-selective thionation of 1 at one of its six amide-bonds, subsequent S-benzylation of the thioamide 2 led to the thioimidate 3, which w
Total synthesis of HUN-7293
Boger, Dale L.,Keim, Holger,Oberhauser, Berndt,Schreiner, Erwin P.,Foster, Carolyn A.
, p. 6197 - 6205 (2007/10/03)
The first total synthesis of the cyclic heptadepsipeptide HUN-7293 (1), a potent inhibitor of cell adhesion molecule expression exhibiting anti-inflammatory properties, is detailed. The most effective approach relied on an unusually efficient macrocyclization with the formation of the MLEU3 - LEU4 secondary amide that potentially benefits from intramolecular H-bonding preorganization of the acyclic substrate. The requisite linear depsipeptide was convergently assembled with the late stage introduction of the linking ester enlisting a Mitsunobu esterification that occurs with inversion of the DGCN α-center permitting the utilization of a readily available L-amino acid precursor to the D α-hydroxy carboxylic acid residue. An alternative and similarly attractive approach of direct macrolactonization of a substrate necessarily incorporating a D-DGCN subunit proved viable albeit less effective. Biological evaluation in cellular assays for vascular adhesion molecule expression confirmed that synthetic HUN-7923 (1) is essentially indistinguishable from the naturally occurring cyclodepsipeptide.
