Fondaparinux sodium disaccharide intermediate fragment BA and synthetic method thereof

A technology of fondaparinux sodium and a synthetic method is applied in the field of synthesis and preparation of disaccharide fragment BA, can solve problems such as unfavorable drug promotion and popularization, unfavorable large-scale production, high product price, etc., and achieves optimized synthetic route and product purification. The effect of convenience and few synthesis steps

Inactive Publication Date: 2013-01-30
麦科罗夫(南通)生物制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] U.S. Patent US4818816 describes a synthetic method for fondaparinoid sodium, which requires about 50 steps, and the yield is only 0.1%. Because the synthetic route is long and the total yield is low, the product price is rel...

Method used

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  • Fondaparinux sodium disaccharide intermediate fragment BA and synthetic method thereof
  • Fondaparinux sodium disaccharide intermediate fragment BA and synthetic method thereof
  • Fondaparinux sodium disaccharide intermediate fragment BA and synthetic method thereof

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specific Embodiment 1

[0033] A Fondaparinux sodium disaccharide intermediate fragment BA, characterized in that: the structural formula of the Fondaparinux sodium disaccharide intermediate fragment BA is: ,among them, R 1 For: -CH 3 ;-C 2 H 5 . R 2 For: -OH; -OAc; -OBz. R 3 For: -OH; -OAc; -OBn. R 4 For: -N 3 ; -NHAc; -NHCBz. R 5 For: -COOH; -COOCH 3 ;-COOC 2 H 5 .

[0034] A method for synthesizing Fondaparinux sodium disaccharide intermediate fragment BA, firstly synthesize ring A and ring B respectively, where ring A is the compound: , Ring B is the compound: ; The A ring and the B ring are coupled into a disaccharide derivative under the action of Lewis acid; the disaccharide derivative is under the action of a base to remove the carboxylic acid group on the B ring to obtain the Fondaparinux sodium disaccharide intermediate Body fragment BA.

[0035] Such as figure 1 As shown, the synthesis process of ring A is as follows:

[0036] Step 1: Preparation of 1-O-methyl 2-acetylamino-2-deoxy-α-D-glucopy...

specific Embodiment ， example 2

[0069] The difference between this embodiment and the first embodiment is: the starting material N-acetyl-glucosamine is charged at 200g; 3-O-benzyl-1,2-O-isopropylidene-6-methyl-α The feed amount of -L-idonic acid is 318 g, and the feed amount of other substances is correspondingly enlarged according to the mass ratio, referring to the operation of each step described in Example 1, to obtain 208 g of Fondaparinux disaccharide intermediate fragment BA.

specific Embodiment ， example 3

[0071] The difference between this embodiment and the first embodiment is that: the starting material N-acetyl-glucosamine dosage is 1kg; 3-O-benzyl-1,2-O-isopropylidene-6-methyl-α -The dosage of L-idonic acid is 1.59kg, and the dosage of other substances should be enlarged according to the mass ratio. Refer to the operation of each step described in Example 1, to obtain 1.17kg of Fondaparinux disaccharide intermediate fragment BA, .

[0072] The invention uses a new synthesis strategy, optimizes the synthesis route, adopts mild reaction conditions, fewer synthesis steps, higher yield, convenient product purification, can effectively scale up for industrialized large-scale production, and has higher economic benefits.

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Abstract

The invention discloses a fondaparinux sodium disaccharide intermediate fragment BA and a synthetic method thereof. The synthetic method is novel in synthesis strategy, available in raw materials, relatively fewer in reaction steps, mild in reaction conditions, simple in post-treatment conditions, easy to operate, low in production cost, high in yield and suitable for large-scale industrial production.

Description

technical field [0001] The present invention relates to the synthesis of disaccharide fragments of a highly selective factor Xa inhibitor, more specifically, the synthesis and preparation method of the disaccharide fragment BA of fondaparinette sodium, the chemical formula of fondaparinette sodium is . Background technique [0002] Blood coagulation is a process in which coagulation factors participate in a series of limited hydrolysis of proteins to form thrombus, including the sequential activation of various coagulation factors and plasma components, among which the generation of FXa is the core step of the blood coagulation process. The X factor activated in the first step of coagulation acts on prothrombin to break the chemical bond between arginine and isoleucine in the prothrombin molecule, forming thrombin with strong protein activity. [0003] Under the action of thrombin, fibrinogen is cleaved, eventually forming stable cross-linked fibrin. At the same time, the...

Claims

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Application Information

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IPC IPC(8): C07H15/18C07H1/00
CPCY02P20/55
Inventor 季春香汤庆刚白东才王娜颜小香王成牛洪森
Owner 麦科罗夫(南通)生物制药有限公司
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