Isolation and Structure of a GD3-Type Ganglioside Molecular Species Possessing Neuritogenic Activity from the Starfish Luidia maculata

Abstract

In the course of our continuing research on biologically active glycosphingolipids (GSLs) from echinoderms, a series of studies on the isolation and structure elucidation of GSLs from starfish have been performed in our laboratory. [1][2][3][4][5][6] In the study of the GSLs of the starfish Luidia maculata (yatsudesunahitode in Japanese), we reported on the isolation, structure and biological activities of cerebrosides, 7) ceramide lactosides, 8) sulfatide, 9) and gangliosides. 10,11) Continuing the previous studies, further isolation and characterization of the more polar ganglioside from L. maculata were conducted. In this paper, we report on the isolation and structure of a ganglioside molecular species from the whole bodies of L. maculata. The biological activity of the ganglioside is also reported.The polar lipid fraction, which was obtained from the chloroform/methanol extract of the whole bodies of L. maculata, was subjected to repeated column chromatography to give a polar compound, designated LMG-4 (1), showing a single spot on silica gel thin-layer chromatography (TLC).Compound 1 shows strong hydroxy and amide absorptions in the IR spectrum and has a positive reaction against resorcinol reagent.12) The negative FAB-MS exhibits a series of quasimolecular ion peaks [MϪH] Ϫ at m/z: 1500-1620. Therefore 1 is suggested to be a molecular species of ganglioside.The structure of the ceramide moiety was examined first. When 1 was methanolyzed with methanolic hydrochloric acid, a mixture of fatty acid methyl esters (FAM) and longchain bases (LCBs) was obtained. The FAM mixture was analyzed by GC-MS, which revealed the presence of three components. These were characterized as methyl 2-hydroxydocosanoate (major), methyl 2-hydroxytricosanoate, and methyl 2-hydroxytetracosanoate. The LCB mixture was found to be composed of such phytosphingosines as 2-amino-1,3,4-trihydroxy-heptadecane (major), 2-amino-1,3,4-trihydroxy-octadecane, and 2-amino-1,3,4-trihydroxy-nonadecane, based on GC-MS analysis of its TMS derivative (Chart 1).The structure of the sugar moiety of 1 was established as follows. The GC analysis of hexitol acetate derivatives of the neutral sugars, which were obtained by hydrolysis, reduction,

Chemical Constituents and Bioactivities of Starfish

“…Moreover, 662 exhibited neuritogenic activity towards the rat pheochromocytoma PC12 cells in the presence of NGF. The effect of 662 was the same as that of the mammalian ganglioside GM 1 [208]. Two gangliosides, LLG-3 (663) [209] and LLG-5 (664) [210], were obtained from the starfish Linckia laevigata.…”

High‐performance separation techniques hyphenated to mass spectrometry for ganglioside analysis

“…The structure of this compound (3, Fig. 2) has been determined on the basis of the same chemical and spectroscopic approach as previously presented for compounds 1 and 2 [44]. GD3-type gangliosides were found to have the composition…”

“…Moreover, the compound 3 exhibited neuritogenic activity toward the rat pheochromocytoma PC12 cells in the presence of nerve growth factor. The isolation and characterization of natural neuritogenically active ganglioside is attracting considerable attention with regard to the possibility to manufacture new drugs from marine natural products [44].…”

Isolation and Structure of Four New Ceramides from the Starfish Luidia maculata

“…From the starfish Luidia maculata, we have isolated and characterized one sulfatide molecular species, 1) six cerebrosides, 2) four ceramide lactosides, 3) and three ganglioside molecular species. [4][5][6] Continuing the previous studies, the isolation and characterization of ceramides from L. maculata were carried out because of the considerable interest and importance connected with determination of the composition of the mixture of sphingolipids and in the hope of discovering the biologically active compounds from marine natural products.In this paper, we report on the isolation and structure determination of four ceramides, LMCer-1-1 (1), LMCer-2-1 (2), LMCer-2-6 (3), and LMCer-2-7 (4) from the starfish L. maculata.The MeOH extract, obtained from the less polar fraction of the CHCl 3 -MeOH extract of the whole bodies of L. maculata, was separated by normal phase silica gel column chromatography to give two substances, LMCer-1 and LMCer-2, which appear as a single spot on the normal phase TLC, and revealed anti-hyperglycemic activity. …”

“…From the starfish Luidia maculata, we have isolated and characterized one sulfatide molecular species, 1) six cerebrosides, 2) four ceramide lactosides, 3) and three ganglioside molecular species. [4][5][6] Continuing the previous studies, the isolation and characterization of ceramides from L. maculata were carried out because of the considerable interest and importance connected with determination of the composition of the mixture of sphingolipids and in the hope of discovering the biologically active compounds from marine natural products.…”