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

• Published in: Chemical & pharmaceutical bulletin Vol. 42; no. 2; pp. 293 - 299
• Main Authors: SHIBUYA, Hirotaka, OHASHI, Kazuyoshi, NARITA, Norihiko, ISHIDA, Toshimasa, KITAGAWA, Isao
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1994; Maruzen; Japan Science and Technology Agency
• Subjects: Ca ionophore; Chemistry; Condensed matter: structure, mechanical and thermal properties; Epoxy Compounds - chemical synthesis; Epoxy Compounds - pharmacology; Erythrocyte Membrane - drug effects; Erythrocyte Membrane - metabolism; Exact sciences and technology; geraniol; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Humans; In Vitro Techniques; ion-permeation activity; ion-transport activity; Ionophores - chemical synthesis; Ionophores - pharmacology; ionophoretic activity; lactone epoxide macrocyclic; Lactones - chemical synthesis; Lactones - pharmacology; Organic chemistry; Organic compounds; Physics; Preparations and properties; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; Terpenes - chemical synthesis; Terpenes - chemistry; Terpenes - pharmacology; Molecular structure; Coronand; Polycyclic compound; Experimental study; Oxygen heterocycle; X ray diffraction; Macrolide; Structure activity relation; Epoxidation; Lactonization; Oxidation; Ionophore; Geraniol; Organic compounds; Crystalline structure
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.42.293

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 (11d), -3 (11e), -4 (11f), -5 (11g), -6 (11h)], was effected by HPLC separation of two diastereomeric tetraepoxides (11a, 11b) 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 (11f) exhibited the strongest ion-transport activity for Ca2+ ion while C2-symmetrical GL2E4-6 (11h) exhibited the strongest ion-permeation activity for Ca2+ ion across the human erythrocyte membrane.