Method for preparing solid-phase synthesized carrier

Abstract

The invention relates to a preparation method of solid phase synthesis carrier, which belongs to the functional high molecular material technology field. The invention adopts halogen acetylized crosslinked polystyrene resin and hydroxybenzyl alcohol as the raw material, and the solid phase synthesis carrier with hydroxymethyl as the active group is synthesized through the joint catalysis of N, N-dimethyl formamide used as the reaction solvent, inorganic base and phase-transfer catalyst. The invention is characterized in that the carrier is produced through the reaction between halogen acetylized crosslinked polystyrene resin and hydroxybenzyl alcohol. Halogen acetylized crosslinked polystyrene resin is used for replacing commonly used methyl chloride polystyrene resin. The method can avoid the use of toxic substances of chloromethyl ether, etc. during the preparation process of methyl chloride polystyrene resin, and also improves the polysubstitution in chloromethylation reaction. Simultaneously, halogen acetyl can react with phenolic hydroxyl singly, thus the competing side reaction between hydroxymethyl and phenolic hydroxyl can be avoided, the phase transition method can avoid the methoxylation side reaction caused by the introduction of organic base; therefore the structure of the product is clear.

Description

technical field [0001] The invention relates to a method for preparing a solid phase synthesis carrier, belonging to the technical field of functional polymer materials Background technique [0002] With the invention of solid-phase synthesis of peptides, solid-phase and combinatorial chemistry technology has achieved remarkable development in recent years, and has become a common method for the synthesis of peptides, proteins, oligonucleotides, and various physiologically active small molecule compounds. [0003] In solid-phase synthesis, a carrier with excellent performance is often the key to the success of the synthesis. The low-crosslinked polystyrene-divinylbenzene resin with various linking functional groups has stable chemical properties, moderate swelling, thermal stability and The mechanical properties are very good, and it is the most widely used solid phase carrier at home and abroad, and among them, Wang resin is widely used. [0004] The traditional Wang resin...

AI Technical Summary

Problems solved by technology

First of all, raw materials such as strong carcinogenic chloromethyl ether or dichloromethyl ether are usually used in the reaction of synthetic raw material chloromethylated polystyrene (Roland L.D.Millar J.R.Chemistry & Industry, 1993, 4(1): 10); In addition, the chloromethylation reaction is also accompanied by multiple substitutions and secondary crosslinking of chloromethyl groups, which will affect the performance of the resin (Barrett J.Heights C.etal.Method of Preparing Anion Exchange Resins with Sulfuryl Chloride[P], US 3,812,061, 1974)

Secondly, sodium methylate will be used in the traditional synthetic method, because methoxy group has stronger nucleophilic substitution, so easily replace active chlorine, cause the generation of methoxylation side reaction (Gui-shen Lu, Svetlana Mojsov, James P. Tam, and R. B. Merrifield. J. Org. Chem. 1981, 46, 3433-3436)