Chemical Transformation of Terpenoids. X. Ionophoretic Activities of Macrocyclic Lactone Epoxides Synthesized from Geraniol

Abstract

Two coronand-type 18-membered lactone epoxides, i. e., geranyl dimeric lactone diepoxide (GL2E2, 10) and tetraepoxide (GL2E4, 11), were synthesized from geraniol as diastereomeric mixtures. Among them, GL2E4 (11) was shown to exhibit ion-transport activity for Ca2+ ion in the test using a W-07 (liquid-membrane type) apparatus and ion-permeation activities for Ca2+and K+ ions across the human erythrocyte membrane. Isolation of six component diastereomers of GL2E4 (11) [GL2E4-1 (11c), -2 (l1d), -3 (l1e), -4 (Ilf), -5 (llg), -6 (llh)], was effected by HPLC separation of two diastereomeric tetraepoxides (11a, l1b) which were prepared from two diepoxides (GL2E2-1, 10a and GL2E2-2, 10b). The relative stereostructures of these diastereomers were determined by a combination of X-ray diffraction and 1H-NMR analyses. Among the six diastereomers, S2-symmetrical GL2E4-4 (I1f) exhibited the strongest ion-transport activity for Ca2+ ion while C2-symmetrical GL2E4-6 (llh) exhibited the strongest ion-permeation activity for Ca2+ion across the human erythrocyte membrane. © 1994, The Pharmaceutical Society of Japan. All rights reserved.