Alkoxyphenyl derivative, nucleoside protector, nucleotide protector, method for producing oligonucleotide, and method for removing substituent

Abstract

The present invention pertains to: an alkoxyphenyl derivative with which oligonucleotides can by synthesized by a liquid-phase synthesis method easier and faster than conventional methods; a nucleoside protector and a nucleotide protector to which the alkoxyphenyl derivative binds; a method for producing an oligonucleotide using same; and a method for selectively removing the alkoxyphenyl derivative moiety. Provided is a compound represented by general formula (1) or a derivative thereof. (In the formula, each R independently represents a C10-40 alkyl group which may be substituted or unsubstituted. m represents an integer of 1-5. When m is 2 or more, the plurality of RO's may be identical or different. X represents O, S, NH, or NRN. n represents an integer of 1-4. RN represents a C1-6 alkyl group which may be substituted or unsubstituted.).

Description

technical field [0001] The present invention relates to an alkoxyphenyl derivative capable of synthesizing oligonucleotides by a liquid-phase synthesis method, and a nucleoside-protected body and a nucleotide-protected body combining the alkoxyphenyl derivative can be easily constructed using the same A method for producing an oligonucleotide, a nucleoside-protected body bound to an alkoxyphenyl derivative or a method for removing a selective alkoxyphenyl derivative portion of a nucleotide-protected body, and the like. Background technique [0002] In recent years, oligonucleotides can generally be synthesized by sequentially linking nucleotides used as raw materials, but in the case of synthesizing oligonucleotides of about 20mer or more, building blocks of 2-3mer nucleotides are also used. The building block synthesis method (brockma-synthesis method) that assembles and links them repeatedly to obtain a product with a desired chain length, and obtains oligonucleotides by l...

AI Technical Summary

Problems solved by technology

The solid-phase synthesis method of oligonucleotides using the phosphoramidite method has the problem of having to use a large excess of nucleoside phosphoramidite compounds and tetrazole-based compounds in order to increase the yield of oligonucleotides as target substances

In addition, in the solid-phase synthesis method, there is a limit to the scale expansion of equipment, etc., and it is difficult to confirm the progress of the reaction in the middle stage and to analyze the structure of the intermediate.

[0003] On the other hand, in the conventional liquid-phase synthesis method, it is difficult to quickly synthesize oligonucleotides with a high degree of polymerization in a large amount due to the need for purification operations in various steps such as deprotection of nucleotides, coupling, and oxidation, which are cumbersome. Nucleotide

Therefore, for example, in Patent Documents 1 and 2, liquid-phase synthesis using a quasi-solid-phase protecting group is proposed, but for example, the removal of the quasi-solid-phase protecting group takes time, and, from an oligonucleotide having a quasi-solid-phase protecting group It is difficult to selectively remove only the quasi-solid-phase protecting group, so the nucleotides (hereinafter, in this specification, sometimes also referred to as "nucleosides") that protect nucleic acid bases or phosphate groups as precursors of building blocks or fragments The synthesis of acid-protected body") is also difficult

In addition, in Non-Patent Document 4, the quasi-solid-phase protecting group is removed by catalytic reduction using a Pd catalyst, but using toxic heavy metals and dangerous hydrogen gas requires a long time of 20 to 40 hours for deprotection.

In addition, the removal of the quasi-solid-phase protecting group under the general deprotection conditions of the protecting group of the nucleotide is not carried out, and there is a problem in its versatility.

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