Studies of peptide antibiotics. XLIII. Syntheses of gramicidin S analogs containing D-serine or dehydroalanine in place of D-phenylalanine and asymmetric hydrogenation of the dehydroalanine residue.
Gramicidin S (GS) analogs, [D-Ser4,4']-GS and its precursor [O-benzyl-D-Ser4,4']-GS, were synthesized by the conventional method in order to evaluate the role of the hydroxymethyl side chains in D-Ser at 4,4' positions on the biological activity. Another analog [L-Orn(delta-Boc)2,2',delta Ala4,D-Ser4']-GS was prepared from [D-Ser4,4']-GS by t-butyloxycarbonylation and successive dehydration using dicyclohexylcarbodiimide-CuCl as dehydrating reagent. The delta Ala residue was asymmetrically hydrogenated to D-Ala in the presence of Pd-black. On the microbial assays, [O-benzyl-D-Ser4,4']-GS showed high antimicrobial activity as natural GS, but [D-Ser4,4']-GS showed low activity; the structure-activity relationships of the analogs were discussed.
D000409:Alanine / Q000031:analogs & derivatives*; D001419:Bacteria / Q000187:drug effects; D006096:Gramicidin / Q000138:chemical synthesis* / Q000494:pharmacology; D007202:Indicators and Reagents; D009904:Optical Rotation; D010649:Phenylalanine; D012694:Serine; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D006096:Gramicidin; D012694:Serine; D010649:Phenylalanine; C015102:dehydroalanine; D000409:Alanine