6 alpha-bromo- androstane-4-ene-3,17-dione high efficient synthesis method

A synthesis method and technology of synthesis method, which are applied in steroids, organic chemistry and other directions, can solve the problems of inability to effectively separate mixtures, difficult to effectively separate, etc., and achieve the effects of cheap and easy availability of reagents, high yield and good reproducibility

Inactive Publication Date: 2007-07-11
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It can be seen that it is difficult to effectively separate the 6β- and 6-α bromoisomers even by column chromatography, and the subsequent elution fractions are still a mixture with the same content of the two and cannot be effectively separated
Since then, the literature has continued to use this difficult method to obtain a trace amount of pure 6α-bromoandrost-4-ene-3,17-dione, and there is no other simple and high yield to obtain pure 6α-bromo-4-AD synthesis and Preparation [3]

Method used

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  • 6 alpha-bromo- androstane-4-ene-3,17-dione high efficient synthesis method
  • 6 alpha-bromo- androstane-4-ene-3,17-dione high efficient synthesis method
  • 6 alpha-bromo- androstane-4-ene-3,17-dione high efficient synthesis method

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Embodiment 1

[0016] Preparation of 6α-bromo-androst-4-ene-3,17-dione

[0017] Configuration translocation method: strong acid as reagent and water as reaction medium

[0018] Add 120 mg of 6β-bromo-androst-4-ene-3,17-dione into 4 mL of concentrated hydrochloric acid, stir at room temperature for 21 hours, add 20 mL of ice water, filter, wash the cake with water until neutral, and dry at room temperature to obtain white 100 mg of powdery solid 6α-bromo-androst-4-ene-3,17-dione, yield 83.33%. Crude 1 H-NMR showed that the 6α-bromo product configuration had been purified. Recrystallized with ethyl acetate to obtain fine product [α] 22 D =+143°(CHCl 3 ), mp: 171-172°C. Ms (m / z, %): 364 (M + , 6.79), 285 (M + -79,100); 1 HNMRδ (400HMz, CDCl 3 ): 0.92 (3H, s, 18-CH 3 ), 1.25 (3H, s, 19-CH 3 ), 4.91 (1H, m, 6-H), 6.45 (1H, s, 4-H).

Embodiment 2

[0020] Preparation of 6α-bromo-androst-4-ene-3,17-dione

[0021] Direct synthesis method: Br 2 / HOAc / THF is the reaction system

[0022] Androst-4-ene-3,17-dione 4.0g, 13.97mmol was dissolved in THF40mL, HOAc 4mL was added, bromine 2.33g, 13.97mmol was added dropwise at room temperature, the dropwise was completed in 15 minutes, and the reaction was basically completed after stirring for 15 minutes. Evaporate THF under reduced pressure at a bath temperature of 40-45°C, analyze with 80 mL of ice water, filter, wash the filter cake with water until it is neutral, and dry it by infrared to obtain the crude yellow solid product 6α-bromo-androst-4-ene- 3,17-diketone 4.96g, yield: 97.2%: mp: 164-165°C turns black and decomposes, crude product determination 1 H-NMR showed that the configuration of the 6α-bromo product was pure. Ethyl acetate recrystallized to obtain fine product[α] 22 D =143°(CHCl 3), mp: 171-172°C. Ms (m / z, %): 364 (M + , 6.79), 285 (M + -79,100); 1 H NMRδ...

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Abstract

The invention discloses an indirect and direct synthesizing method of 6 alpha-bromine-androster-4-olefin-3, 17-diketone, which comprises the following steps: 1. using strong acid to transmit 6 beta-bromine-androster-4-olefin-3, 17-diketone in the water to obtain pure 6 alpha-bromine-androster-4-olefin-3, 17-diketone; 2. synthesizing 6 alpha-bromine-androster-4-olefin-3, 17-diketone based on androster-4-olefin-3, 17-diketone as raw material in the Br2 / HOAc / THF; affirming stereoscopic structure of two-method product consistent through X-diffraction.

Description

technical field [0001] The invention belongs to the field of organic chemistry and medicine synthesis, and specifically relates to a highly efficient synthesis method of compound 6α-bromo-androst-4-ene-3,17-dione. Background technique [0002] Aromatase (Aromatase) is an important enzyme in the biosynthesis of estrogen in vivo. Aromatase inhibitors have become an important area of ​​research for drugs that treat estrogen-associated cancers. A series of bromo-4-en-3-one steroid compounds have been reported in the literature, such as: 6 α and 6 β-bromo-androst-4-ene-3,17-dione and its 2,2-dimethyl 6-Bromocompounds such as derivatives have significant aromatase inhibitory activity, but the pharmacological mechanisms of the two are different [ 1. Francis L. Bellino, Syed S.H. Gilani, Sik S. Eng, § Yoshio Osawa, * and William L.DuaxActive-Site-Directed Inactivation of Aromatase from Human Placental Microsomes by Brominated Androgen Derivatives Biochemistry.1976, 15(21), 4730-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J1/00
Inventor 夏鹏陈瑛
Owner FUDAN UNIV
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