A homodimer synthesis process of fkbp ligand

Abstract

The invention discloses a synthesis process of homodimer of FKBP ligand and belongs to an improved synthesis process of AP1903, wherein the homodimer of FKBP ligand refers to AP1903. According to theoptimized route of the synthesis process chooses, (S)-piperidine-2-methyl formate is connected to the compound Cpd9' as selected, an acid Cpd6' obtained after ester hydrolysis is easier to be purified by post-treatment purification, and precipitation or extraction treatment can be chosen by the post-treatment purification. Although the total reaction steps of the synthetic route in the prior literature are the same as the optimized route of the invention, the synthetic route in the prior literature belongs to the vertical route, and the post-treatment of the fifth, sixth and eighth steps requires column chromatography, thereby leading to a higher research and development cost. The optimized AP1903 synthetic route belongs to the parallel route, and the post-treatment is simpler and more advantageous for separation and purification, so that the cost of research and development is relatively low and the economic benefit is obviously superior to that of the synthetic route in the prior art.

Description

technical field [0001] The invention belongs to the technical field of synthesis technology of dimerization agent, and in particular relates to an improved synthesis technology of homodimer AP1903 of FKBP modified ligand. Background technique [0002] AP1903 is a dimerization agent with the molecular formula C 78 h 98 N 4 o 20 , with a molecular weight of 1411.63, is a homodimer of FKBP-modified ligands. In cells or animals expressing FKBP appropriate signaling domain fusion proteins, AP1903 can be used to trigger signal transduction, but due to the binding of ligands to endogenous FKBP, the The use of homodimers in vivo is severely limited. The solubility of AP1903 in dimethyl sulfoxide is >23.5mg / ml. In order to obtain higher solubility of AP1903 solution, heat the test tube containing the solution to 37°C, then shake the test tube in an ultrasonic bath for a while, and the solution can be Store at temperatures below -20°C for several months. AP1903 acts by cross-...

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Problems solved by technology

[0004] like figure 1 as shown, figure 1 It is the synthesis route diagram of AP1903 in the prior art literature report, the synthesis route in the prior art literature belongs to the vertical route, and the post-processing of steps 5, 6, and 8 all require column chromatography, and the research and development cost is relatively high

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