Studies on the chemical Modification of Monensin. III. Synthesis and Sodium Ion transport Activity of macrocylic Monenslamino Acid-1, 29-lactones

Abstract

Monensylglycine (2a) was lactonized to macrocyclic monensylglycine-1, 29-lactone (3a) by Corey's mehtod. Lactonization of monensylamino acids (2b-d) to monensylamine 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 membra he and in guinea pig erythrocyte membrane. Monensylaspartic acid-1, 29-lactone (3d), 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.