Synthesis method of peptide nucleic acid cytosine monomer

Abstract

The invention provides a synthesis method of a peptide nucleic acid cytosine monomer. The preparation method comprises the following steps: 1) dissolving 4-N-(diphenylmethoxycarbonyl)-cytosine)-1-acetic acid in N, N-dimethylformamide, adding N-hydroxysuccinimide while stirring, adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride at 0 DEG C, stirring and reacting at room temperature, and displaying that the reaction is finished through TLC (Thin Layer Chromatography); and 2) dissolving N-(2-Fmoc-aminoethyl) glycine in N, N-dimethylformamide, adding the active ester obtained in the step 1), dropwise adding N, N-diisopropylethylamine at 0 DEG C, and reacting at room temperature overnight to obtain the required product peptide nucleic acid cytosine monomer. The reaction route is simplified, and the reaction condition is mild; the use of acyl chloride is avoided, and anhydrous and anaerobic operation is not needed; the used solvent can be recycled, and is green and environment-friendly; and a basis is provided for industrialization of the peptide nucleic acid cytosine monomer.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis, in particular to a method for synthesizing a peptide nucleic acid cytosine monomer. Background technique [0002] Peptide nucleic acid, a class of DNA analogs that replace the sugar phosphate backbone with a polypeptide backbone, is a new nucleic acid sequence-specific reagent that Danish organic chemist Ole Buchardt and biochemist Peter Nielsen began to study in the 1980s. It is a third-generation antisense reagent designed and constructed by computer and finally artificially synthesized on the basis of the first and second generation antisense reagents. The 2-aminoethylglycine bond replaces the pentose phosphodiester bond backbone in DNA, and the rest is the same as DNA. PNA can recognize and bind DNA or RNA sequences through Watson-Crick base pairing to form a stable double helix structure. [0003] According to the metabolic stability of PNA, it is mainly used in the field of ant...

AI Technical Summary

Problems solved by technology

[0006]At present, no company in China can carry out large-scale industrialization of this product, and its synthesis scale generally only reaches the gram level, which is only suitable for research and cannot provide long-term stable commodity supply

Among them, the synthesis process route is long and the operation is cumbersome, which is the bottleneck of large-scale synthesis of peptide nucleic acid cytosine monomer

[0007] There are many problems in the existing peptide nucleic acid cytosine monomer synthesis process, the synthesis route is long, the process is complicated, the yield is low, and the operation is cumbersome; the reaction uses anhydrous and oxygen-free conditions; the feeding ratio is difficult to control, resulting in increased by-products

Especially in the step of synthesizing the final product, since the two protecting groups may fall off under the reaction conditions, it is difficult to grasp the reaction yield, and it is difficult to remove impurities in the subsequent treatment.

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