Glycopyrrolate compounds and synthesis method thereof

A synthesis method and pyrrolose technology, applied in chemical instruments and methods, sugar derivatives, sugar derivatives, etc., can solve the problems of large amount of original drug, high price, no synthesis process, etc., and achieve easy synthesis and solve the shortage of sources. , the effect of simple process

Inactive Publication Date: 2011-11-16
DALIAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Extracting and separating glycopyrrole alkaloids from natural medicinal materials requires a large amount of raw material

Method used

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  • Glycopyrrolate compounds and synthesis method thereof
  • Glycopyrrolate compounds and synthesis method thereof
  • Glycopyrrolate compounds and synthesis method thereof

Examples

Experimental program
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[0031] The present invention further provides a method for synthesizing the above-mentioned pyrrolidose compound, described as method i in this specification, comprising the following steps:

[0032]The other hydroxyl groups except one hydroxyl group of the monosaccharide are protected, and the unprotected hydroxyl group is oxidized to carbonyl group to form an oxime, which is further reduced to an amino compound, and then reacted with 2,5-dimethoxytetrahydrofuran to generate a pyrrolose compound.

[0033] Specifically, the synthetic method i comprises the steps:

[0034] (1) select one of the following methods to carry out hydroxyl protection:

[0035] a. Acetone sulfuric acid introduces isopropylidene protection;

[0036] b. Acetone sulfuric acid, using copper sulfate as a catalyst to introduce isopropylidene protection;

[0037] In above-mentioned steps (1), preferred method a. acetone sulfuric acid introduces isopropylidene protection, namely

[0038] (2) select one of ...

Embodiment 1

[0077] Example 1: Synthesis of 1-pyrrole fructose

[0078] (1) Synthesis of 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranose (1)

[0079]

[0080] Compound 1

[0081] In a 250mL three-necked flask, add 100mL of acetone, 3mL of concentrated sulfuric acid, stir and cool, add 7.5g of D-fructose in batches at 25°C, react at room temperature for 3 hours, neutralize with 1N sodium hydroxide, filter, evaporate the acetone, recrystallize, 6.5 g of white solid were obtained, and the yield was 60.0%.

[0082] (2) Synthesis of 2,3:4,5-bis-O-(1-methylethylidene)-β-D-fructopyranosaldehyde (2)

[0083]

[0084] Compound 2

[0085] Add 300mL CH to the 1000mL three-necked flask 2 Cl 2 , add 35mL pyridine, add 23g CrO 3 . 15.08 g of diacetone fructose (1) was weighed and added to the reaction solution, and then 8.2 mL of acetic anhydride was added, and the reaction temperature was controlled at 20°C-25°C. TLC detected that the reaction was complete, 500 mL of ethyl acetate w...

Embodiment 2

[0103] Example 2: Synthesis of 1-pyrrole fructose by imidazole sulfonate method

[0104] (1) Synthesis of 1-O-imidazolesulfonyl-2,3:4,5-bis-O-(1-methylethylene)-β-D-fructopyranose (7)

[0105]

[0106] Compound 7

[0107] Under nitrogen protection, in a 5000mL three-necked flask, sequentially add 52.0g diacetone fructose, 15.0g imidazole, and 1000mL DMF, cool down to -5°C, add 30g sulfuryl chloride dropwise with stirring, stir for 0.5h, warm up to room temperature and react for 1h, Diethyl ether and ice water were added, the aqueous phase was extracted, the organic phases were combined, washed with brine, dried, evaporated to remove the solvent, and subjected to column chromatography to obtain 62.5 g of solid with a yield of 80.0%. Melting point: 75-76℃, [α] D -27° (c 7.4, MeOH). 1 HNMR (400MHz, CDCl 3 ): δ8.03(s, 1H), 7.36(s, 1H), 7.19(s, 1H), 4.58(dd, J=7.9, 2.6Hz, 1H), 4.25(d, J=10.2Hz, 1H) , 4.21 (dd, J=7.9, 0.7Hz, 1H), 4.18 (d, J=2.6Hz, 1H), 4.16 (d, J=10.2Hz, 1H)...

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Abstract

The invention discloses glycopyrrolate compounds, which are compounds formed by connecting deoxidized saccharide hydroxyl and a pyrrole ring, and have a structure shown as a general formula I or II, wherein R1, R6, R10, R15 and R16 are independently selected from -H, -OH and monosaccharide hydroxyl protective group; and n1 and n2 are independent integers ranging from 1 to 6. Saccharide ring and pyrrole connected compounds designed and synthesized in the technical scheme are important intermediates for synthesizing natural saccharide quinazoline alkaloid by a chemical method. A problem that biological sources of the compounds are insufficient can be solved; and the technological process is concise, and the compounds are easy to synthesize.

Description

technical field [0001] The present invention designs a new type of pyrrolidose compound, which is synthesized through a mature synthesis process. It belongs to the technical field of organic synthesis of pharmaceutical synthesis methods and pharmaceutical synthesis intermediates. technical background [0002] Pyrrolose compounds have many applications in different medical fields, such as the treatment of neurological diseases, etc. The US Food and Drug Administration approved Cuvposa (glycopyrrolate) oral solution on July 28, 2010 to treat children aged 3 to 16 years old Chronic severe salivation due to neurological disorders. In recent years, a unique class of glycopyrrole alkaloids has been found in different parts of various plants. In 2003, Tu Pengfei et al. isolated six new alkaloid compounds from Astragalus membranaceus (Ma Xiaofeng et al. Research on the chemical constituents of Astragalus mongolica, Shenyang Medicine University of Science and Technology Doctoral Di...

Claims

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Application Information

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IPC IPC(8): C07H19/044C07H1/00
CPCY02P20/55
Inventor 霍世勇赵伟杰李悦青王世盛张旭梁超雁刘季红宋其玲
Owner DALIAN UNIV OF TECH
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