萜类化合物的化学转化。X. 由香叶醇合成的大环内酯环氧化物的离子载体活性。

Chemical transformation of terpenoids. X. Ionophoretic activities of macrocyclic lactone epoxides synthesized from geraniol.

作者信息

Shibuya H, Ohashi K, Narita N, Ishida T, Kitagawa I

机构信息

Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.

出版信息

Chem Pharm Bull (Tokyo). 1994 Feb;42(2):293-9. doi: 10.1248/cpb.42.293.

DOI:10.1248/cpb.42.293

PMID:8149455

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 (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.

摘要

两种冠醚型18元内酯环氧化合物，即香叶醇二聚内酯二环氧化物（GL2E2，10）和四环氧化物（GL2E4，11），由香叶醇合成，为非对映异构体混合物。其中，在使用W - 07（液膜型）仪器进行的测试中，GL2E4（11）对Ca2 +离子表现出离子转运活性，并且对Ca2 +和K +离子表现出跨人红细胞膜的离子渗透活性。通过高效液相色谱法分离由两种二环氧化物（GL2E2 - 1，10a和GL2E2 - 2，10b）制备的两种非对映异构体四环氧化物（11a，11b），实现了GL2E4（11）的六种组分非对映异构体[GL2E4 - 1（11c），-2（11d），-3（11e），-4（11f），-5（11g），-6（11h）]的分离。这些非对映异构体的相对立体结构通过X射线衍射和1H - NMR分析相结合来确定。在这六种非对映异构体中，S2对称的GL2E4 - 4（11f）对Ca2 +离子表现出最强的离子转运活性，而C2对称的GL2E4 - 6（11h）对Ca2 +离子表现出最强的跨人红细胞膜的离子渗透活性。