Synthesis of (-)-DAPD.

A new synthesis of (-)-DAPD, suitable for large scale development, is described.

Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta)--synthesis and biological activity.

We report the synthesis and biological activity of a new series of small molecule agonists of the human Peroxisome Proliferator-Activated Receptor delta (PPARdelta). Several hits were identified from our original libraries containing lipophilic carboxylic acids. Optimization of these hits by structure-guided design led to 7k (GW501516) and 7l (GW0742), which shows an EC(50) of 1.

New synthesis of L-FMAU from L-arabinose.

A new synthesis of 2'-deoxy-2'-fluoro-5-methyl-beta-L-arabinofuranosyl uracil (13, L-FMAU) was achieved in 10 steps from L-arabinose.

Studies on the total synthesis of tallysomycin. Synthesis of the threonylbithiazole moiety containing a structurally unique glycosylcarbinolamide.

[structure: see text]. Tallysomycins are glycopeptide antibiotics that were first isolated from fermentation broths of Streptoalloteichus hindustanus. They are structurally related to the bleomycins but contain an additional talose sugar attached via a unique glycosylcarbinolamide linkage.

A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport.

The peroxisome proliferator-activated receptors (PPARs) are dietary lipid sensors that regulate fatty acid and carbohydrate metabolism. The hypolipidemic effects of the fibrate drugs and the antidiabetic effects of the glitazone drugs in humans are due to activation of the alpha (NR1C1) and gamma (NR1C3) subtypes, respectively. By contrast, the therapeutic potential of the delta (NR1C2) subtype is unknown, due in part to the lack of selective ligands.