Studies on chemical modification of monensin. V. Synthesis, sodium ion permeability, antibacterial activity, and crystal structure of 7-O-(4-substituted benzyl)monensins.
7-O-(4-Substituted benzyl)monensins (3a-g) were synthesized from monensin (1), and their lipophilicity, antibacterial activity, and Na+ ion permeability were examined. 7-O-(4-Ethylbenzyl)monensin (3e) showed the largest Na+ ion permeability, but 3c,f,g showed smaller Na+ ion permeability than 7-O-benzylmonensin (2) in spite of higher lipophilicity. An X-ray study of the sodium salt of 3e revealed that the benzyl group was located over the position between the D and E rings, and that the ethyl substituent on the benzyl group was close to the C(28) methyl group on the E ring.
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
A
A
Nagatsu
T
T
Takahashi
M
M
Isomura
S
S
Nagai
T
T
Ueda
N
N
Murakami
J
J
Sakakibara
K
K
Hatano
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D008985:Monensin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012964:Sodium / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D008985:Monensin; D012964:Sodium