JP2640977B2 - Glycosphingolipids - Google Patents

Description

The present invention relates to glycosphingolipids derived from the starfish Acanthaster planci.

[Conventional technology and its problems]

Glycosphingolipids are components of lipid bilayers that form cell membranes of animals and plants, and are said to be involved in cell differentiation, mutual recognition and the like.

Conventionally, several species of glycosphingolipids such as cerebroside (ceramide-monohexoside) ceramide-dihexoside and ganglioside have been obtained from starfishes belonging to the phylum Echinoderm (T. Komori et al, Liebigs Ann. Chem., 1980,
653), all of which remain mixtures (molecular species) with different compositions of ceramide (long-chain base and fatty acid). Structural analysis and bioactivity studies on isolated glycosphingolipids have been conducted. Absent.

[Means for solving the problem]

The present inventors have reported that the sea star, Acanthas
A novel ganglioside was isolated from ter planci) and its structure was determined, which was found to be a compound represented by the following formula (I).

That is, the present invention provides the following formula (I) Wherein R represents a linear alkyl group having 10 to 25, preferably 13 to 21 carbon atoms, and R 'represents a linear alkyl group having 10 to 20, preferably 11 to 17 carbon atoms. It provides glycolipids.

Glycosphingolipids (I) of the present invention can be obtained, for example, by converting a starfish to chloroform and alcohols (particularly methanol).
After extraction with a mixed solvent and concentration, the solvent fractionation is performed, and the water-soluble fraction can be obtained by purification by reverse phase and normal phase column chromatography. In the tissues of the starfish, in addition to the glycosphingolipid (I) of the present invention, the following formula (II) (Wherein R and R 'are the same as those described above). Glycosphingolipids represented by the following formula are also available. In this purification step, the glycosphingolipid (II) was subjected to silica gel chromatography [solvent: n-butanol-chloroform-isopropanol]. -Methanol-14% ammonia (1: 2: 1:
4: 1.5)].

As typical examples of the glycosphingolipid of the present invention, R = CH _{2 19} CH ₃ and R ′ = CH _{2 11} CH _{3 in the} formula (I)
And R = CH _{2 21} CH ₃ and R ′ = CH _{2 11} CH ₃ , which are further separated by means such as reverse phase HPLC using MeoH-H ₂ O-PicA. Is possible.

Since the glycosphingolipid (I) of the present invention has a cerebral cortical nerve cell survival maintaining effect, it is useful as a therapeutic agent for neurodegenerative diseases such as senile dementia, Alzheimer's disease and Parkinson's disease.

〔Example〕

 Next, the present invention will be described in more detail with reference to examples.

Example 1 52 kg of chloroform-methanol extract was distributed in a mixture of water and ethyl acetate-n-butanol, and the obtained aqueous layer was extracted with water-saturated n-butanol. The aqueous layer was further concentrated to dryness, extracted with a chloroform-methanol mixture, and the chloroform-methanol-soluble portion was purified by reversed-phase and normal-phase column chromatography to obtain normal-phase TL.
Two-component AG-2 (1.2 g) showing a single spot on C and AG-
3 (620 mg) was obtained.

Example 2 AG-3 obtained as described above has an IR similar to AG-2.
Showed amide absorption, and ¹³ C NMR analysis revealed that it was a phytosphingosine-type ceramide molecular species having an oxyfatty acid.

The sugar moiety was determined by ¹³ C NMR and trimethylsilyl (TMS) conversion of the product of methanolysis of AG-3, and the analysis revealed that 4 mol of galactose (Gal), N-acetylneuraminic acid (NANA), and glucose (Glc) were 1 each. It was clarified to be composed of moles, and the binding order of each sugar was determined to be terminal hexose → hexose → hexose → NANA → hexose → hexose from fragmentation in negative FABMS.

Alditol obtained from fully methylated AG-3-
Analysis of acetate and methanolizate acetate by GC-MS analysis of terminal hexofuranose (1 mol), 4-position bond
The presence of NANA (1 mol), 3-linked hexopyranose (2 mol) and 4-position-linked hexopyranose (2 mol) was found.

When AG-3 was heated at 80 ° C. in an aqueous solution and partially hydrolyzed, ceramide-lactoside and oligosaccharide were obtained. Further, alditol acetate analysis was performed on the partially methylated ceramide-lactoside obtained by partial methanolysis of the fully methylated form of AG-3, and from the results, NANA (2 → 4) GalP (1 → 4) was obtained. ) The existence of a partial structure of Glc-ceramide was found.

Based on the above-mentioned chemical knowledge, ¹³ C NMR analysis of AG-3, and the signal of anomeric hydrogen on ¹ H NMR of the fully methylated product, AG-3 was determined to be a mixed species of the compound represented by formula (I). Was done.

AG-3: mp 164-166 ° C Negative FABMS (m / z) [1727,1741,1755 [MH] ⁻ ] [1593,1431,1269,978,816,654 (main fragment ions)] ¹³ C NMR [69.9, 51.1,75.4,72.5,176.0,72.6 (ceramide)] [110.5,104.9,104.2,101.9,100.9,97.3 (anomeric carbon)] separation of example 3 AG-3 _{components, MeOH-H 2 O-PicA} * Reversed-phase HPLC using [column: ERC-2151, 3μ solvent: 97% MeOH-PicA (1
00: 5) Flow rate: 1.2 ml / min], AG-3-3 and AG
-3-5 was isolated. And the structure of this thing is ¹³ C NM
R, identification of fatty acid methyl esters obtained by methanolysis and identification of negative FABMS.

Claims (2)

(57) [Claims] 1. The following formula (I) (Wherein, R represents a linear alkyl group having 10 to 25 carbon atoms, and R ′ represents a linear alkyl group having 1 to 20 carbon atoms). 2. R is a straight-chain alkyl group having 13 to 21 carbon atoms;
Is a straight chain alkyl group having 11 to 17 carbon atoms.