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Ganglioside GM3 derivative and preparation method and application thereof

A compound, C3-C10 technology, applied in the field of medicine and chemical industry, can solve the problems of expensive reaction reagents, harsh reaction conditions, long steps of chemical total synthesis, etc.

Pending Publication Date: 2022-02-25
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the process of chemical synthesis, it is necessary to carry out multi-step protection and deprotection operations on sugars, and it is also necessary to consider the regioselectivity and stereochemical selectivity of glycosidic bond formation. These factors greatly increase the difficulty of synthesis, and because the total chemical synthesis steps are too long, The required reagents are expensive and the reaction conditions are harsh

Method used

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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0136] The preparation method of intermediate compound IV

[0137] Preferably, the preparation method of compound IV of the present invention comprises steps:

[0138] (ii) in a buffer solution (eg, containing Mg 2+ HEPES solution), in the presence of enzymes (such as Neu5Ac aldolase, CMP-sialic acid synthase and sialyltransferase), compound A4

[0139] Compound A1 Cytidine triphosphate (CTP) and pyruvate react to obtain the compound of formula IV

[0140] Z and R 1 is defined as above.

[0141] Preferably, the preparation method of the compound of formula IV also includes the step

[0142]

[0143] (i) In a buffer solution (eg, NaAc solution), in the presence of an enzyme (eg, EGCase glycoside synthase), fluorinated lactose and sphingosine Reaction, obtain compound A4

[0144] active ingredient

[0145] As used herein, "active ingredient", "compound of the present invention" and "ganglioside GM3 derivative" refer to compounds shown in formula I, and also ...

Embodiment 1

[0213] Example 1 Synthesis of ganglioside GM3 (α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-Cer)

[0214]

[0215] Step 1: Synthesis of Compound Lactose-Sphingosine

[0216]

[0217] Reactions were performed in 50 mM, pH 5.8 NaAc buffer containing 0.1% Triton X-100. The total reaction system is 100 mL, wherein the final concentration of the substrate sphingosine is 0.5 mM, the final concentration of fluorinated lactose is 1 mM, and the final concentration of pure EGCase glycoside synthase enzyme solution is 25 μg / mL. The reaction system was placed in a constant temperature water bath at 37°C for 48-72h. After the reaction, boil in a boiling water bath for 5 minutes to inactivate the EGCase glycoside synthase, and centrifuge at 12000 r / min for 30 minutes to remove the inactivated enzyme. After centrifugation, the supernatant was processed to obtain lactose-sphingosine.

[0218] Step 2: One-pot synthesis of α-Neu5Ac-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-Cer

[0219] Reactions contai...

Embodiment 2

[0220] Example 2 Synthesis of ganglioside GM3 (α-Neu5Prop-(2-3)-β-Gal-(1-4)-β-Glc-(1-1)-Cer)

[0221]

[0222] Referring to Example 1, ManNAc was replaced by ManNPro, and the yield was 40%. 1 H NMR (400MHz, CD 3 OD)δ5.99–5.78(m,1H),5.53–5.37(m,1H),4.08–3.33(m,19H),2.30–2.16(m,3H),2.20–2.03(m,2H),2.00 (s,2H),1.56(q,J=7.3Hz,3H),1.40(q,J=7.6Hz,2H),1.28(d,J=9.1Hz,51H),0.88(t,J=6.6Hz ,6H).

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PUM

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Abstract

The invention provides a ganglioside GM3 derivative and a preparation method and application thereof. Specifically, the invention relates to a ganglioside GM3 derivative which has a structure as shown in a formula I. The ganglioside GM3 derivative has a remarkable growth promoting effect on nerve cells, has no obvious inhibiting and killing effects on the nerve cells under a relatively high dosage, and has relatively high safety. The invention further relates to a synthesis method of the ganglioside GM3 and the derivative thereof, the ganglioside GM3 and the derivative thereof can be efficiently and controllably synthesized, in addition, the compound ganglioside GM3 derivative can be used for preparing other glycosphingolipid derivatives.

Description

technical field [0001] The present invention relates to a technical field of medicine and chemical industry, in particular, the present invention relates to ganglioside GM3 derivatives and their preparation methods and applications. Background technique [0002] Glycosphingolipids are widely present in the cell membranes of various tissues of vertebrates, and are a class of amphipathic glycolipid compounds, composed of ceramide (including two modules of sphingosine and fatty acid) and oligosaccharide chains (including multiple monosaccharide modules) with glycosidic bonds. connected to form. Glycosphingolipids are composed of modules such as oligosaccharide chains, sphingosine, and fatty acids. Changes in any module can produce different glycosphingolipid structures. It is estimated that there are more than 100,000 types of glycosphingolipids in nature. [0003] These molecules are widely involved in the biochemical signal transduction between cells and the outside world, a...

Claims

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Application Information

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IPC IPC(8): C07H15/10A61K31/7032A61K31/7048A61P3/10A61P25/00A61P9/00A61P35/00A61P9/10A61P25/28A61P31/00A61P25/16C12P19/44
CPCC07H15/10A61P3/10A61P25/00A61P9/00A61P35/00A61P9/10A61P25/28A61P31/00A61P25/16C12P19/44
Inventor 傅磊王君韬姜发琴吕丹张勇吴金鸿孙冉雷纾雯
Owner SHANGHAI JIAO TONG UNIV
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