Studies of peptide antibiotics. XLVI. Syntheses of gramicidin S analogs containing D-alpha,beta-diaminopropionic acid or alpha,beta-dehydroalanine.
A gramicidin S (GS) analog ([D-Dpr4,4'] GS) containing D-alpha,beta-diaminopropionic acid (D-Dpr) in place of D-Phe at 4,4' positions was derived from [L-Orn(delta-formyl)2,2', D-Dpr(beta-Z)4,4']GS, which was synthesized by conventional method in solution. An analog [delta Ala4,4']GS was synthesized from [L-Orn(delta-Boc)2,2', D-Dpr4,4']GS through Hofmann degradation of the D-Dpr residues. Antimicrobial activities of these analogs were tested; [D-Dpr(beta-Z)4,4']GS and [delta Ala4,4']GS showed high antimicrobial activities against Gram-positive bacteria. [D-Dpr4,4']-GS showed an appreciable activity against Gram-negative bacteria such as Escherichia coli. Four semigramicidin S (semiGS) analogs such as [delta Ala4]semiGS were synthesized; these had no antimicrobial activity. Analogs containing delta Ala residues were hydrogenated, and the formation of L-Ala or D-Ala residues was determined. The delta Ala residues in [delta Ala4,4'] GS were reduced to DL-Ala, and delta Ala in [delta Ala4]semiGS mostly to L-Ala. The relationships of the antimicrobial activity, CD curves and asymmetric hydrogenation to the structure were discussed.
Ando
S
S
Kato
T
T
Izumiya
N
N
D000409:Alanine / Q000031:analogs & derivatives; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006096:Gramicidin / Q000138:chemical synthesis* / Q000494:pharmacology; D006865:Hydrogenation; D013329:Structure-Activity Relationship; D015091:beta-Alanine / Q000031:analogs & derivatives
D015091:beta-Alanine; D006096:Gramicidin; C011757:2,3-diaminopropionic acid; C015102:dehydroalanine; D000409:Alanine