- Site-selective epimerization of a fungal cyclodepsipeptide via a 5- aminooxazole intermediate
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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
- Oberhauser, Berndt,Baumann, Karl,Grohmann, Brigitte,Sperner, Hildegard
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- Solution-phase parallel synthesis of a pharmacophore library of HUN-7293 analogues: A general chemical mutagenesis approach to defining structure-function properties of naturally occurring cyclic (depsi)peptides
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HUN-7293 (1), a naturally occurring cyclic heptadepsipeptide, is a potent inhibitor of cell adhesion molecule expression (VCAM-1, ICAM-1, E-selectin), the overexpression of which is characteristic of chronic inflammatory diseases. Representative of a gene
- Chen, Yan,Bilban, Melitta,Foster, Carolyn A.,Boger, Dale L.
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p. 5431 - 5440
(2007/10/03)
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- Total synthesis of HUN-7293
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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.
- Boger, Dale L.,Keim, Holger,Oberhauser, Berndt,Schreiner, Erwin P.,Foster, Carolyn A.
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p. 6197 - 6205
(2007/10/03)
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