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A kind of functional carbohydrate molecule based on tdg molecular skeleton and preparation method thereof

A sugar and aryl technology, applied in the field of functional sugar molecules based on the TDG molecular skeleton and its preparation, can solve the problems of unreported, blocking signal channels, and insignificant biological effects, etc., and achieve a wide range of applications, The effect of stable response and obvious application value

Active Publication Date: 2022-07-12
SHENZHEN INST OF ADVANCED TECH
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Problems solved by technology

[0006] At present, the utilization of TDG sugar ligand molecules is basically limited to the medicinal chemical application of TDG sugar ligand molecules as galectin protein inhibitors, which mainly block the binding of galectin target proteins through the competitive binding of TDG sugar ligand molecules. The binding of the galectin target protein to the natural sugar ligand or antibody in the organism can block the corresponding signal channel and exert the corresponding biological effect. However, the current research results show that the biological effect is not obvious, and the related reasons need to be further studied
[0007] In addition to the medicinal chemistry applications of TDG sugar ligands, there is no research on the use of TDG sugar ligand molecules to recognize and combine with galectin proteins, and to use TDG sugar ligand molecules as functional molecules targeting galectin proteins. However, functional molecules that can play the role of the target of these sugar ligand molecules have not been reported

Method used

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  • A kind of functional carbohydrate molecule based on tdg molecular skeleton and preparation method thereof
  • A kind of functional carbohydrate molecule based on tdg molecular skeleton and preparation method thereof
  • A kind of functional carbohydrate molecule based on tdg molecular skeleton and preparation method thereof

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Experimental program
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Effect test

Embodiment 1

[0109]

[0110] Diacetone glucose (40 g, 153.7 mmol) dissolved in Ac 2 O / DMSO (v / v=1:2, 150mL) mixed solution, stirred at room temperature overnight, TLC (PE:EA=1:1) detected the reaction was complete, the reaction solution was diluted with dichloromethane DCM, washed with water 3 times, The organic phases were combined, washed with 30% hydrogen peroxide, dried over anhydrous sodium sulfate, and concentrated to obtain a brown syrup intermediate, which was directly used in the next step.

[0111] The brown syrup intermediate was dissolved in pyridine (50 mL), acetic anhydride (20 mL) was added dropwise, and the reaction was placed in an oil bath at 90°C and refluxed overnight. TLC (PE:EA=1:1) detected that the reaction was complete, and the reaction solution was cooled to room temperature. After concentration, it was purified by column chromatography (isocratic elution, PE:EA=3:1) to obtain colorless syrup I-1 (39.5 g, 85% in 2steps). 1 H NMR (400M, CDCl 3 )δ6.04(d,J=5.5Hz...

Embodiment 2

[0113]

[0114] Compound 1-1 (39.5 g, 131.5 mmol) was dissolved in ethyl acetate (100 mL), Pd / C powder (2.0 g) was added, and after stirring, it was placed in a hydrogen (40 psi) atmosphere and stirred for 3 hours. TLC (PE: EA=1:1) Check that the reaction is complete, filter out the Pd / C powder, and concentrate the filtrate to obtain a pale yellow syrup intermediate (36.6g, 92%), 1 H NMR (400MHz, CDCl3) δ 5.82 (d, J=4.1Hz, 1H), 5.10-5.06 (m, 1H), 4.81 (dd, J=5.6, 4.1Hz, 1H), 4.14-4.06 (m, 2H), 3.57-3.51(m, 1H), 2.14(s, 3H), 1.59(s, 3H), 1.45(s, 3H), 1.39(s, 3H), 1.36(s, 3H). 13 C NMR (101MHz, CDCl3)δ 169.7, 114.6, 109.4, 105.1, 81.5, 78.6, 75.3, 71.9, 66.5, 26.9, 26.8, 25.4, 20.7.

[0115] The light yellow syrup obtained in the previous step was dissolved in methanol (100 mL), sodium methoxide was added to adjust the pH of the reaction solution to 8-10, stirred at room temperature for 30 min, TLC (PE:EA=1:1) showed that the reaction was complete, and 732 type H was added. ...

Embodiment 3

[0117]

[0118] Compound I (29.9 g, 114.88 mmol) was dissolved in dichloromethane (100 mL), pyridine (27.81 mL, 344.6 mmol) was added, and after cooling to ice bath temperature, trifluoromethanesulfonic anhydride (38.6 mL, 229.7 mmol) was added dropwise, Stir under ice bath for 30min, TLC (PE:EA=1:1) showed that the reaction was complete, the reaction solution was successively passed through 1N HCl a.q. , sat. NaHCO 3a.q.Washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain a brown syrup intermediate, which was directly used in the next reaction;

[0119] Azidotrimethylsilane (52.9 mL, 402.1 mmol) and sodium fluoride (15.9 g, 379.1 mmol) were mixed with DMF (150 mL), refluxed in an oil bath at 100 °C for 1 hour, cooled to room temperature, and added with The DMF solution of the brown syrup intermediate obtained in the first step, the mixture was placed in a 50 ° C oil bath to reflux for overnight reaction, TLC (PE:EA=1:1) detected tha...

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Abstract

The present invention designs a saccharide compound whose structure is shown in formula X, wherein R 1 , R 2 independently selected from substituted amido, substituted triazolyl, substituted amino; R 3 Selected from sulfhydryl, azide, amino, carboxyl; A is or -C m H 2m R 3 , X is selected from oxygen atoms; n is selected from 0, 1, 2, 3, 4, 5, 6, 7; m is selected from 2, 3, 4, 5, 6, 7, 8, 9, 10. The present invention adopts the synthesis strategy of "first side chain derivatization, then glycosylation coupling", realizes the side chain derivatization modification of the TDG molecular skeleton, and realizes the efficient synthesis of compounds. The invention utilizes the recognition and binding of TDG sugar ligand molecules to the target protein, and plays the role of the target head that recognizes and binds to the target protein, and uses it as the target head molecule to construct functional targeting molecules, which has wide application in the fields of tumor detection, tumor immunity and the like prospect.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a functional carbohydrate molecule based on a TDG molecular skeleton and a preparation method thereof. Background technique [0002] Galectin is a class of lectin proteins, belonging to sugar-binding proteins, which can recognize and bind sugars with galactose and lactose residues through its own Carbohydrate Recognition Domain (CRD) pocket. Ligand molecules play an important role in many physiological and pathological processes (such as cancer, inflammation, etc.). [0003] At present, the recognition and binding mechanism of galectin protein and its sugar ligand molecules has been elucidated, and a series of sugar ligand molecules with high specific recognition and high affinity binding to galectin have been developed (WO 2005 / 113569 A1, WO 2016 / 113335 A1, WO 2017 / 019770 A1, WO 2017 / 080973 A1), wherein sugar ligand molecules with thiodigalactoside (TDG) molecular backbone ca...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/056C07H1/00A61P29/00A61P35/00G01N33/574G01N33/68
CPCC07H19/056C07H1/00A61P29/00A61P35/00G01N33/57488G01N33/68Y02P20/55
Inventor 李伟王怀雨
Owner SHENZHEN INST OF ADVANCED TECH
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