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4 - dihydroxy boryl - l-phenylalanine preparation method

A technology of hydroxyboronyl phenylalanine and halophenylalanine, which is applied in the field of preparation of 4-dihydroxyboronyl-L-phenylalanine, and can solve the problem of low L-BPA yield, inapplicability, etc. problem, to achieve the effect of high cost efficiency, saving time and shortening the process

Inactive Publication Date: 2015-03-25
TAIWAN BIOTECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0016] In addition, Synlett.1996, 167 disclosed a method for coupling reaction of iodophenylborate and L-serine zinc derivatives (L-serine zinc derivatives), which first involves the preparation of iodophenylborate Esters and preparation of zinc derivatives of L-type serine and other steps, resulting in a lower yield of L-BPA
In addition, due to the choice of rich 10 boron triiodide 10 Boron and 1,3-diphenylpropane-1,3-diol are not commercially available compounds, so the method provided in this document is still not suitable for the synthesis of rich 10 Boron L-BPA

Method used

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  • 4 - dihydroxy boryl - l-phenylalanine preparation method

Examples

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Effect test

Embodiment 1

[0100] (1) Preparation of (S)-N-tert-butoxycarbonyl-4-dihydroxyboryl-phenylalanine from (S)-N-tert-butoxycarbonyl-4-iodophenylalanine

[0101] Please refer to the following reaction formula (I), which is the reaction of (S)-N-tert-butoxycarbonyl-4-iodophenylalanine with tributyl borate to synthesize (S)-N-tert-butoxycarbonyl- The chemical reaction formula of 4-dihydroxyborylphenylalanine.

[0102]

[0103] First, a 1-liter three-necked bottle equipped with a mechanical stirrer, a thermometer, and a nitrogen gas inlet joint sealed with a rubber gasket was prepared. Inject 150 milliliters of 2-methyltetrahydrofuran into the three-necked flask, and then add 24.7 millimoles (10.0 grams, purity 96.8%) of (S)-N-tert-butoxycarbonyl-4-iodophenylalanine, The two were uniformly stirred to form a solution; then, 77.8 mmol (17.9 g, 21 ml) of tributyl borate was added to the solution to form a mixed solution.

[0104] Next, the mixed solution was cooled to between -85°C and -76°C, and...

Embodiment 2

[0132] (1) Prepare (S)-N-tert-butoxycarbonyl-4-( 10 B) Dihydroxyboryl phenylalanine

[0133]First, a 3-liter three-necked bottle equipped with a mechanical stirrer, a thermometer, and a nitrogen inlet joint sealed with a rubber gasket was prepared. Inject 750 milliliters of 2-methyltetrahydrofuran into the three-necked flask, then add 128 millimoles (50.0 grams, 100% purity) of (S)-N-tert-butoxycarbonyl-4-iodophenylalanine, And the two were uniformly stirred to form a solution; after that, 393 mmol (90.1 g, 106 ml) of 10 Tributyl borate was added to the solution to form a mixed solution.

[0134] Next, the mixed solution was cooled to between -85°C and -76°C, and a 1.6M (600 mmol, 375 ml) hexane solution of n-butyllithium was added dropwise to the mixed solution over 3 hours to A reaction mixture is obtained.

[0135] Then, the reaction mixture was stirred at -80°C for 0.5 hours, and a small amount of the reaction mixture sample was quickly added to water and analyzed by H...

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Abstract

The invention provides a 4 - dihydroxy boryl - L-phenylalanine preparation method which is as follows: reacting amino terminal-protected (S) - 4 -halogeno phenylalanine shown as the formula (I) with a boriding agent and an organic lithium compound to obtain a reaction mixture containing amino terminal-protected (S) - 4 - dihydroxy boryl phenylalanine shown as the formula (II) with R being a protective group; separating the reaction mixture to obtain the amino terminal-protected (S) - 4 - dihydroxy boryl phenylalanine; and de-protecting the amino terminal-protected (S) - 4 - dihydroxy boryl phenylalanine to obtain 4 - dihydroxy boryl - L-phenylalanine.

Description

technical field [0001] The present invention relates to a kind of preparation method of the boride that utilizes boron neutron capture therapy to treat cancer, relate in particular to a kind of 4-( 10 B) The preparation method of dihydroxyboryl-L-type phenylalanine. Background technique [0002] 4-( 10 B) dihydroxyboryl-L-type phenylalanine (4-( 10 B) borono-L-phenylalanine, L- 10 BPA) is an important boron compound known to be able to treat cancer with boron neutron capture therapy (BNCT). [0003] Therefore, various synthesis methods of L-BPA have been developed at present. As shown in the following formula (A), the L-BPA synthetic method of the prior art includes two modes of forming a bond (a) and a bond (b): [0004] [0005] Among them, the method for synthesizing L-BPA by forming the bond (a) is to try to introduce a substituent containing a dihydroxylboryl group (dihydroxylboryl group or borono group) into the skeleton of phenylalanine, thus in the pair of am...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02
CPCY02P20/55C07F5/025
Inventor 许坤旺黄淑芬萧家政
Owner TAIWAN BIOTECH
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