Steroid n-glycoside analogue taking dihydro-pyranoid ring as D ring and preparation and application thereof

A technology of dihydropyran ring and steroidal nitrogen glycosides, which is applied in the field of organic chemistry and achieves the effect of simple preparation method and mild conditions

Active Publication Date: 2012-03-28
PHARMARON BEIJING
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Nucleoside compounds modified by the glycosyl moiety have attracted widespread attention due to their good antitumor and antiviral activities. In recent years, many research reports have been published, and the types of new compounds have increased rapidly. However, for the glycosyl moiety D The synthesis of steroidal nitrogen glycoside analogs with dihydropyran ring structure has not been reported yet

Method used

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  • Steroid n-glycoside analogue taking dihydro-pyranoid ring as D ring and preparation and application thereof
  • Steroid n-glycoside analogue taking dihydro-pyranoid ring as D ring and preparation and application thereof
  • Steroid n-glycoside analogue taking dihydro-pyranoid ring as D ring and preparation and application thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0034] Preparation of the general formula R 1 is methylsulfonyl, R 2 is a chlorine atom, R 3 Derivatives when it is a hydrogen atom, that is, compound f (3β-sulfonyl ester group-17α-(6′-chloropurine-9′-)-D-homocyclic-17a-oxa-5α-androster) preparation.

[0035] Step 1: Synthesis of compound b (3β-hydroxy-D-homocyclo-17a-oxa-5α-androst-17-one)

[0036] Take compound a (5g, 17.2mmol) in a 500mL flask, add dichloromethane (50mL) and stir to dissolve, then add methanol (250mL) and distilled water (60mL), add MMPP (8.5g, 17.2mmol) to the reaction system under stirring at room temperature ), then add the same amount of MMPP every 24h, react for 4d, and stop the reaction after the thin-layer chromatography detects that the reaction is complete; ) extraction, the organic phases were combined and washed with 10% sodium hydroxide (10mL×3) until the pH of the aqueous phase was alkaline, then washed with saturated brine (20mL×3), anhydrous Na 2 SO 4 Dry, and finally concentrate under...

Embodiment 2

[0050] Example 2 prepares R shown in the general formula 1 is methylsulfonyl, R 2 is a chlorine atom, R 3 When it is a chlorine atom, the compound g(3β-sulfonyl ester group-17α-(2′,6′-dichloropurinyl-9′-)-D-homocycle-17a-oxa-5α- androster) preparation

[0051] Add 211mg of trifluoroacetic acid to the ethyl acetate solution (50mL) of compound e (1g, 2.7mmol), then add the base 2,6-dichloropurine, heat up and reflux for 24h, lower the temperature of the system to room temperature, and depressurize The organic solvent was distilled off to obtain a white solid, and dichloromethane was added to dissolve the white solid, and the organic phase was washed with 5% NaOH solution, anhydrous Na 2 SO 4 The organic phase was dried, and the organic solvent was distilled off under reduced pressure to obtain a white solid, which was recrystallized from ethanol to obtain a white needle-like solid, that is, compound g (3β-sulfonyl ester-17α-(2′,6′-dichloropurinyl-9 '-)-D-homocyclo-17a-oxa-5...

Embodiment 3

[0053] Example 3 prepares R shown in the general formula 1 is methylsulfonyl, R 2 is a chlorine atom, R 3 When it is a derivative of a fluorine atom, the compound h(3β-sulfonyl ester group-17α-(2′-fluoro-6′-chloropurinyl-9′-)-D-homocycle-17a-oxa-5α - androster) preparation

[0054] Add 211mg of trifluoroacetic acid to the ethyl acetate solution (50mL) of compound e (1g, 2.7mmol), then add the base 2-fluoro-6-chloropurine (1.0g, 5.4mmol), heat and reflux for 24h, and The temperature of the system was lowered to room temperature, and the organic solvent was distilled off under reduced pressure to obtain a white solid. Add dichloromethane to dissolve the white solid, wash the organic phase with 5% NaOH solution, anhydrous Na 2 SO 4 The organic phase was dried, and the organic solvent was distilled off under reduced pressure to obtain a white solid, which was recrystallized from ethanol to obtain a white needle-like solid, namely compound h (3β-sulfonyl ester group-17α-(2′-fl...

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Abstract

The invention belongs to the technical field of organic chemistry, relates to an n-glycoside analogue and in particular relates to a steroid n-glycoside analogue taking a dihydro-pyranoid ring as a D ring and a preparation and an application thereof. The steroid n-glycoside analogue taking the dihydro-pyranoid ring as the D ring has significant inhibition effects against a variety of tumor cell strains, such as the cell strains of prostatic cancer, human neuroblastoma and the like, and can be used for preparing anti-tumor medicaments. The steroid n-glycoside analogue taking the dihydro-pyranoid ring as the D ring is prepared trough five-step reactions, namely oxidation, hydroxyl protection, reduction, selective oxidation and glycosidation, the preparation method is simple and the conditions are mild.

Description

technical field [0001] The invention belongs to the technical field of organic chemistry, and relates to a nitrogen glycoside analog, in particular to a steroidal nitrogen glycoside analog whose D ring is a dihydropyran ring, and its preparation and application. Background technique [0002] Cancer is one of the most common and serious diseases that directly threaten human life in the world today. In my country, cancer ranks second among the top ten major diseases. Therefore, the development of anti-cancer drugs with high efficiency and low side effects has always attracted great attention from scientific research institutions and pharmaceutical companies in various countries. Nucleoside analogues (nucleoside analogue, NA) are an important class of anticancer chemotherapeutic agents, including derivatives of various purine and pyrimidine nucleosides. The synthesis of purines, pyrimidines, purine nucleotides and pyrimidine nucleotides required in synthesis and DNA synthesis ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J73/00A61K31/58A61P35/00
Inventor 黄利华刘宏民王艳广郑永飞赵兵
Owner PHARMARON BEIJING
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