Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B0 derivatives

Selective methanolysis or dehydration followed by reduction of the 3-hydroxyglutamine residue of pneumocandin B0 (1) or its dideoxy analog 5 (L-692,289) gave the methyl 3-hydroxyglutamate and 3-hydroxyornithine analogs 6 and 9, respectively. Further derivatization of these analogs allowed a study of the SAR at this position. In general, carboxylic acid-containing derivatives were poorer antifungal agents than neutral derivatives while amine-bearing analogs displayed the greatest potency.