Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Process for synthesizing 6-18F-L-dopa

A synthesis process and preparation process technology, applied in the field of synthesis process of radioactive substance 6-18F-L-dopa, can solve the problem of shortening the total radiochemical synthesis time of precursors, etc. The effect of high rate and easy availability of raw materials

Inactive Publication Date: 2003-04-09
NAN FANG HOSPITAL
View PDF0 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Purpose of the present invention is exactly in order to overcome current 6- 18 The shortcoming of the synthesis technique of F-L-dopa, provide a kind of synthesis technique simple, total radiochemical synthesis time shortens, the physicochemical property of precursor is stable and does not need to purify first synthetic technique

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Process for synthesizing 6-18F-L-dopa

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] (K / K / 222) +18 f - preparation of

[0017] Using a cyclotron through 18 O(p,n) 18 F nuclear reaction, continuous bombardment of 1.5mL H with 16.5MeV, 25μA proton beam 2 18 O target 30~60min, production 18 f - . contain 18 f - After the target water passes through the anion-exchange column QMA post produced by Waters, other anion-exchange columns can also be used to use the acetonitrile aqueous solution containing potassium carbonate, the phase transfer catalyst Kryptofix 222 between the crown ether liquid phases produced by Sigma or Merck Rinse, and other crown ethers can also be used to collect the eluate. Take part of the eluent, heat at 120°C, and blow dry with nitrogen to obtain a white solid residual active complex (K / K / 222) +18 f - .

[0018] The acetonitrile aqueous solution of potassium carbonate and crown ether is preferably acetonitrile water (96 / 4, v / v) solution containing potassium carbonate 4mg (0.029mmol) and 22mg (0.058mmol) Kryptofix 222. Th...

Embodiment 2

[0020] 6-[ 18 F] Preparation of fluoropiperonal (3)

[0021] To the above residue, add a DMSO (1 mL) solution containing 12-17 mg of 6-nitropiperonal (2) (Mr 195, 0.061-0.087 mmol), seal it, and heat at 135° C. for 20 min. Cool the reaction mixture, add 20 mL of water, pass through a C18 Sep-Pak column, wash with 5 mL of 0.5 mol / L hydrochloric acid and 10 mL of water respectively, discard the washing solution, and 6-[ 18 F] Fluoropiperonal (3) was retained on the C18Sep-Pak column. Rinse with a small amount of ether, and the radiochemical purity determined by HPLC and TLC is greater than 95%. HPLC analysis: C18 column, mobile phase is methanol / water (volume ratio is 65:35, pH=4, containing acetic acid 0.05mol / L), flow rate is 0.7mL / min; TLC analysis: chromatographic solution is 100% dichloro methane.

Embodiment 3

[0023] 2-[ 18 F] Preparation of fluoro-4,5-methylenedioxybenzyl bromide (4)

[0024] NaBH 4 15 mg dissolved in H 2 O 0.5mL, through the C18 Sep-Pak column, 6-[ 18 F] fluoropiperonal (3) is reduced to generate 6-[ 18 F] Fluoropiperol, add water 5mL and n-hexane 5mL rinse respectively, 6-[ 18 F] Fluoropiperol remains on the column. with NaBr and concentrated H 3 PO 4 The reaction prepares HBr gas, and the dried HBr gas passes through the C18 Sep-Pak column, 6-[ 18 F] fluoropiperol rapidly (within 30s) bromination reaction occurs with HBr on the column to generate 2-[ 18 F] Fluoro-4,5-methylenedioxybenzyl bromide (4) remained on the column. Rinse the C18Sep-Pak column with 1.5-2.5 mL of anhydrous toluene, and pass the eluent through anhydrous K 2 CO 3 Short column, directly used for the next step of alkylation reaction. The radiochemical purity was greater than 95% as determined by TLC. Conditions: The chromatographic solution is 100% dichloromethane.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The synthesis process 6-18F-L-Dopa (18FDOPA) with 6-nitro piperonaldehyde as precursor includes four steps: nucleophilic fluorination, reducing bromination, chiral phase transferring catalytic alkylation and hydrolysis. The process has high production efficiency, no need of purifying precursor, easy to purify final product, and low cost. The product may be used in animal experiment and conventional clinical application.

Description

technical field [0001] The present invention relates to radioactive substances 6- 18 Synthetic process of F-L-dopa. Background technique [0002] 6-[ 18 F] fluoro-L-3,4-dihydroxyphenylalanine (6-[ 18 F] fluoro-L-dopa, 6-[ 18 F]fluoro-L-dopa, 18 FDOPA) is an analogue of L-dopa. It is a positron imaging agent for studying the presynaptic dopaminergic nerve function of the brain. It has been widely used in the diagnosis of early Parkinson's disease and the differential diagnosis of some tumors. 18 The development of FDOPA and its clinical application have been reported in a large number of literatures abroad, but there is no one in China. 18 FDOPA research report. There are two main synthesis methods, namely electrophilic substitution reaction and nucleophilic substitution reaction. The synthesis steps of the electrophilic substitution reaction method are simple and convenient, and the radiochemical yield is relatively high. 18 FDOPA is more commonly used method. Howev...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07C227/12C07C229/36
Inventor 唐刚华
Owner NAN FANG HOSPITAL
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com