Synthesis and biological evaluation of photoaffinity labeled fusidic acid analogues.

Novel photoaffinity labeled fusidic acid analogues were obtained by a synthetic sequence employing a Wittig reaction between a fusidic acid aldehyde and benzyl bromides in the key step. Three commonly used photoreactive groups, benzophenone, trifluoromethyldiazirine, and aryl azide, were used. The photoaffinity labeled fusidic acid analogues demonstrated a potent antibacterial activity (MIC 0.

SmI2 reduced thioesters as synthons of unstable acyl radicals: direct synthesis of potential protease inhibitors via intermolecular radical addition.

Aromatic alpha-heterosubstituted thioesters were found to undergo radical 1,4-addition reactions to a series of alpha,beta-unsaturated amides and one ester when subjected to the single electron reducing agent, samarium diiodide, at -78 degrees C. These thioesters derived from alpha-amino acids represent a synthetically useful synthon of unstable acyl radicals. This reaction conveniently provides access to gamma-ketoamides and esters in yields up to 90%, structures that are common in various protease inhibitors derived from peptides.

SmI(2)-promoted radical addition of nitrones to alpha,beta-unsaturated amides and esters: synthesis of gamma-amino acids via a nitrogen equivalent to the ketyl radical.

[reaction: see text] Alkyl nitrones undergo radical addition reactions to a series of alpha,beta-unsaturated amides and esters when subjected to samarium diiodide via a nitrogen equivalent to a ketyl radical anion. This reaction conveniently provides access to a variety of functionalized gamma-amino acids. The methodology was extended to the asymmetric synthesis of 4-substituted gamma-amino acids, via the nitrone radical addition reaction to acrylates/amides possessing a chiral auxiliary.