Studies on the chemical modification of monensin. III. Synthesis and sodium ion transport activity of macrocyclic monensylamino acid-1,29-lactones.
Monensylglycine (2a) was lactonized to macrocyclic monensylglycine-1,29-lactone (3a) by Corey's method. Lactonization of monensylamino acids (2b--d) to monensylamino acid-1,29-lactones (3b--d) was carried out by utilizing the template effect of K+ ion. Monobenzyl esters of dicarboxylic monensylamino acids (5e--f) also were lactonized followed by debenzylation to yield carboxylic monensylamino acid-1,29-lactones (3e--f). Sodium ion transport activity of monensin (1) and the lactones (3) was measured in a liquid membrane and in guinea pig erythrocyte membrane. Monensylaspartic acid-1,29-lactone (3e) exhibited 2.5 times higher activity than 1 in the liquid membrane. Monensylalanine-1,29-lactone (3b), monensylphenylalanine-1,29-lactone (3c), and monensyltyrosine-1,29-lactone (3d), having smaller Na+ ion transport activity than 3e, showed weak antibacterial activity, while 3e was inactive in biological tests, probably due to the lower lipophilicity.
Nakamura
A
A
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Nagai
S
S
Ueda
T
T
Murakami
N
N
Sakakibara
J
J
Shibuya
H
H
Kitagawa
I
I
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D008985:Monensin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats
D008985:Monensin