KR19990079446A - Deprotection of hydroxy groups using tetrabutyl ammonium peroxy disulfate - Google Patents

Deprotection of hydroxy groups using tetrabutyl ammonium peroxy disulfate Download PDF

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KR19990079446A
KR19990079446A KR1019980012073A KR19980012073A KR19990079446A KR 19990079446 A KR19990079446 A KR 19990079446A KR 1019980012073 A KR1019980012073 A KR 1019980012073A KR 19980012073 A KR19980012073 A KR 19980012073A KR 19990079446 A KR19990079446 A KR 19990079446A
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trityl
tetrabutyl ammonium
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hydroxy group
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KR100273171B1 (en
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김용해
양승각
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박호군
한국과학기술연구원
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    • C—CHEMISTRY; METALLURGY
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    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H1/00—Processes for the preparation of sugar derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
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    • C07H19/06—Pyrimidine radicals

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Abstract

본 발명은 무수상태의 유기 용매 하에서 하기 구조식을 갖는 테트라부틸 암모늄 퍼옥시 디술페이트 (tetra-n-butylammonium peroxydisulfate)를 이용하여 온화한 중성 상태에서 트리틸 유도체들로 보호된 히드록실기를 갖는 뉴클레오시드,뉴클레오티드 또는 t-부틸 디메틸 실릴(t-butyldimethylsilyl), 케탈(ketal) 등으로 보호된 히드록시기를 갖고 있는 알코올과 반응시켜 중성인 무수상태에서,히드록시기들의 탈보호화 반응에 관한 것이다.The present invention relates to a nucleoside having hydroxyl groups protected with trityl derivatives in a mild neutral state using tetra-n-butylammonium peroxydisulfate having the following structural formula in an organic solvent in an anhydrous state. The present invention relates to a deprotection reaction of hydroxy groups in a neutral anhydrous state by reaction with an alcohol having a hydroxy group protected with nucleotides or t-butyldimethylsilyl, ketal, and the like.

Description

테트라부틸 암모늄 퍼옥시 디술페이트를 이용한 히드록시기의 탈보호화 방법Deprotection Method of Hydroxy Group Using Tetrabutyl Ammonium Peroxy Disulfate

본 발명은 테트라부틸 암모늄 퍼옥시 디술페이트 (tetra-n-butylammonium peroxydisulfate)를 이용하여 수분이 없는 상태에서 히드록시기의 탈보호화 반응에 관한 것이다. 보다 상세하게는 핵산화학에서 5'-히드록시기의 보호화 및 탈보호화반응은 매우 중요한 반응으로서 테트라부틸 암모늄퍼옥시디수페이트를 이용하여 중성조건에서 탈보호하는 새로운 반응에 관한 것이다.The present invention relates to the deprotection reaction of hydroxy groups in the absence of moisture by using tetra-n-butylammonium peroxydisulfate. More specifically, the protection and deprotection of 5'-hydroxy groups in nucleic acid chemistry is a very important reaction and relates to a new reaction of deprotection in neutral conditions using tetrabutyl ammonium peroxydisulfate.

뉴클레오시드나 뉴클레오티드에서 5'-히드록시 보호화는 여러 종류의 올리고뉴클레오티드의 합성시에 이용되며, 트리틸(trityl)기나 그 유도체들이 당, 뉴클레오시드, 스테로이드 등의 5'-히드록시기를 보호하는 작용기로 널리 이용되어 왔다.5'-hydroxy protection in nucleosides or nucleotides is used in the synthesis of various oligonucleotides, and trityl groups or derivatives thereof protect 5'-hydroxy groups such as sugars, nucleosides and steroids. It has been widely used as a functional group.

본 발명과 관련된 종래기술로서 2'-디옥시뉴클레오시드의 5'-트리틸그룹을 ZnBr2를 이용하여 탈보호화반응(Tetrahedron Letters, M.D. Mattencci& Caruthers 1980, 21, pp3243-3246)과 포름산을 이용하여 산성조건에서 트리틸 유도체들의 보호기들을 탈보호화 시키는 반응(Ttrahedron Letters, M.Bessodes, D.Komiotisand K. Antonakis, 1986, 27, pp579-580)이 발표되어 있다. 그러나 이들의 문제점은 과량의 ZnBr2(5-10당량)를 사용해야하며, 산성조건에서의 트리틸기의 탈보호화반응시킬 경우에는 뉴클레오시드의 글리코시딕 C-N결합이 파괴되어 부가 반응이 일어나는 것으로 알려져 있다.As a related art of the present invention, a 5'-trityl group of 2'-deoxynucleoside is deprotected using ZnBr 2 (Tetrahedron Letters, MD Mattencci & Caruthers 1980, 21, pp3243-3246) and formic acid. To deprotect the protecting groups of trityl derivatives under acidic conditions (Ttrahedron Letters, M. Besodes, D. Komiotisand K. Antonakis, 1986, 27, pp 579-580). However, their problem is that excessive ZnBr 2 (5-10 equivalents) should be used, and in the case of deprotection of trityl group under acidic conditions, it is known that addition reaction occurs due to the breakdown of glycosidic CN bond of nucleoside. have.

상기의 문제점들을 해결하기 위하여 본 발명자들은 비교적 온화한 조건에서 반응이 진행되며, 위험하지 않고, 환경 유해성이 적은 테트라부틸 암모늄 퍼옥시 디술페이트 (tetra-n-butyl ammonium peroxydisulfate)를 이용하여 뉴클레오시드의 5'-히드록시기의 탈보호화 반응에 관한 연구를 거듭한 끝에 본 발명을 완성하게 되었다. 본 발명자들이 개발한 방법으로 반응을 실시한 바에 의하면, 종래에 산성 조건에서 쉽게 파괴되던 글리코시딕 C-N결합이 전혀 영향을 받지 않고, 온화한 조건에서도 매우 좋은 수율로 탈보호화가 이루어짐을 발명하게 되었다. 또한 본 발명에서는 다른 알코올 보호기, 즉 t-부틸 디메틸 실릴, 이소프로필리덴 케탈, 헥실리덴 케탈에는 전혀 영향을 주지 않았다.In order to solve the above problems, the inventors of the present invention proceed with the reaction under relatively mild conditions, and are not dangerous. After repeated studies on the deprotection reaction of the 5'-hydroxy group, the present invention was completed. According to the present invention, the reaction was carried out by the method developed by the present inventors, and thus, the glycosidic C-N bond, which was conventionally easily broken under acidic conditions, was not affected at all, and the deprotection was achieved in a very good yield even under mild conditions. In addition, the present invention had no effect on other alcohol protecting groups, i.e., t-butyl dimethyl silyl, isopropylidene ketal, hexylidene ketal.

5'-(4,4'-디메톡시트리틸)염 과 테트라부틸 암모늄 퍼옥시 디술페이트를 무수 아세토니트릴 용매하에서 반응은 다음과 같다.The reaction of 5 '-(4,4'-dimethoxytrityl) salt with tetrabutyl ammonium peroxy disulfate in anhydrous acetonitrile solvent is as follows.

이상과 같이 본 발명의 특징은, 테트라부틸 암모늄 퍼옥시 디술페이트(Tetra-n-butylammonium peroxydisulfate)를 이용한 뉴클레오시드의 5'-히드록시기의 선택적 탈보호화와 유용성에 있다.As described above, the feature of the present invention lies in the selective deprotection and usefulness of the 5'-hydroxy group of nucleosides using tetra-n-butylammonium peroxydisulfate.

이하에서는 실시 예를 근거로 하여 본 발명을 보다 상세히 설명하고자 하며 본 발명의 범위가 이들 실시예에 국한되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples, and the scope of the present invention is not limited to these Examples.

(실시예 1)(Example 1)

5'-(4,4'-디메톡시트리틸) 유리딘 (546 mg, 1 mmol) 과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol) 을 무수 아세토니트릴 (5 ml) 용매하에서 50oC 조건으로 2시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온하여 용매를 증발 농축 시킨다. 그 후에 크로마토 그래피 (실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 에틸 아세테이트 : 이소프로필 알코올 : 물 = 4 : 1 : 2)를 통하여 208 mg (85 %)의 유리딘을 얻었다.5 '-(4,4'-dimethoxytrityl) uridine (546 mg, 1 mmol) and tetrabutyl ammonium peroxy disulfate (1.35 g, 2 mmol) were dissolved in anhydrous acetonitrile (5 ml) in a solvent at 50 °. The reaction was carried out under C conditions for 2 hours. After the starting material is removed, the solvent is concentrated by evaporating the temperature at room temperature. Chromatography (silica gel column; 20 cm × 3 cm, Merck 70-230, solvent; ethyl acetate: isopropyl alcohol: water = 4: 1: 1) gave 208 mg (85%) of uridine .

1H NMR (DMSO-d6) d 3.59 (q, 2H), 3.85 (m, 1H), 3.97-4.05 (m, 2H), 5.10 (br, 2H), 5.39 (br, 1H), 5.67 (d, 1H), 5.79 (d, 1H), 7.90 (d, 1H). 1 H NMR (DMSO-d 6 ) d 3.59 (q, 2H), 3.85 (m, 1H), 3.97-4.05 (m, 2H), 5.10 (br, 2H), 5.39 (br, 1H), 5.67 (d , 1H), 5.79 (d, 1H), 7.90 (d, 1H).

(실시예 2)(Example 2)

5'-(4,4'-디메톡시트리틸) 티미딘 (544 mg, 1 mmol)과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol)을 무수 아세토니트릴 (5 ml) 용매하에서 50oC 조건으로 2시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온으로 하여 용매를 증발 농축 시킨다. 그 후에 크로마토 그래피( 실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 염화 메틸렌 : 메탄올 = 10 : 1)를 통하여 218 mg (90 %)의 티미딘을 얻었다.5 '- (4,4'-dimethoxy trityl) thymidine (544 mg, 1 mmol) and tetrabutylammonium sulfate peroxy disulfide (1.35 g, 2 mmol) to 50 o Under anhydrous acetonitrile (5 ml) solvent The reaction was carried out under C conditions for 2 hours. After the starting material is removed, the solvent is concentrated by evaporating the temperature at room temperature. Chromatography (silica gel column; 20 cm × 3 cm, Merck 70-230, solvent; methylene chloride: methanol = 10: 1) afforded 218 mg (90%) of thymidine.

1H NMR (DMSO-d6) d 1.75 (s, 3H), 2.02-2.08 (m, 2H), 3.53-3.57 (m, 2H), 3.73-3.74 (m, 1H), 5.02 (t, 1H), 5.21-5.23 (d, 1H), 6.11-6.18 (t, 1H), 7.68 (s, 1H), 11.4 (br,1H). 1 H NMR (DMSO-d 6 ) d 1.75 (s, 3H), 2.02-2.08 (m, 2H), 3.53-3.57 (m, 2H), 3.73-3.74 (m, 1H), 5.02 (t, 1H) , 5.21-5.23 (d, 1 H), 6.11-6.18 (t, 1 H), 7.68 (s, 1 H), 11.4 (br, 1 H).

(실시예 3)(Example 3)

5'-(4,4'-디메톡시트리틸)-2'-디옥시유리딘 (530 mg, 1 mmol)과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol)을 무수 아세토니트릴 (5 ml) 용매하에서 50oC 조건으로 2시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온으로 내린 다음, 용매를 증발 농축시킨다. 그런 다음 크로마토 그래피 (실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 염화 메틸렌 : 메탄올 = 10 : 1)를 통하여 201 mg (88 %)의 디옥시 유리딘을 얻었다.5 '-(4,4'-dimethoxytrityl) -2'-dioxyuridine (530 mg, 1 mmol) and tetrabutyl ammonium peroxy disulfate (1.35 g, 2 mmol) were dried with anhydrous acetonitrile (5 ml) under a solvent at 50 ° C. for 2 hours. After the starting material is removed, the temperature is lowered to room temperature, and then the solvent is concentrated by evaporation. Chromatography (silica gel column; 20 cm × 3 cm, Merck 70-230, solvent; methylene chloride: methanol = 10: 1) gave 201 mg (88%) of dioxy uridine.

1H NMR (DMSO-d6) d 2.02-2.15(m, 2H), 3.54-3.59(m, 2H), 3.78-3.79(m, 1H), 4.21-4.25(m, 1H), 5.02(br, 1H), 5.26(br, 1H), 5.64-5.67(d, 1H), 7.86-7.87(d, 1H), 11.5(br, 1H). 1 H NMR (DMSO-d 6 ) d 2.02-2.15 (m, 2H), 3.54-3.59 (m, 2H), 3.78-3.79 (m, 1H), 4.21-4.25 (m, 1H), 5.02 (br, 1H), 5.26 (br, 1H), 5.64-5.67 (d, 1H), 7.86-7.87 (d, 1H), 11.5 (br, 1H).

(실시예 4)(Example 4)

5'-(4,4'-디메톡시트리틸)-2',3'-이소프필리덴 유리딘 (625 mg, 1 mmol)과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol)을 무수 아세토니트릴 (5 ml) 용매하에서 50oC 조건으로 2시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온으로 하여 용매를 증발 농축 시킨다. 그런 다음 크로마토그래피(실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 염화 메틸렌 : 메탄올 = 10 : 1)를 통하여 300 mg (93 %)의 2',3'-이소프로필리덴 유리딘을 얻었다.5 '-(4,4'-dimethoxytrityl) -2', 3'-isopropylidene uridine (625 mg, 1 mmol) and tetrabutyl ammonium peroxy disulfate (1.35 g, 2 mmol) The reaction was carried out under acetonitrile (5 ml) solvent at 50 ° C. for 2 hours. After the starting material is removed, the solvent is concentrated by evaporating the temperature at room temperature. Then 300 mg (93%) of 2 ', 3'-isopropylidene glass via chromatography (silica gel column; 20 cm x 3 cm, Merck 70-230, solvent; methylene chloride: methanol = 10: 1) Dean got it.

1H NMR (DMSO-d6) d 1.15 (s, 3H), 1.37 (s, 3H), 3.50-3.68 (m, 2H), 4.08 (dd, 2H), 4.68 (m, 2H), 5.46 (d, 1H), 5.63 (d, 1H), 7.47 (d, 1H), 10.5 (br, 1H). 1 H NMR (DMSO-d 6 ) d 1.15 (s, 3H), 1.37 (s, 3H), 3.50-3.68 (m, 2H), 4.08 (dd, 2H), 4.68 (m, 2H), 5.46 (d , 1H), 5.63 (d, 1H), 7.47 (d, 1H), 10.5 (br, 1H).

(실시예 5)(Example 5)

5'-(4,4'-디메톡시트리틸)-2'-3'-헥실리덴-D-리본닉-감마-락톤 (530 mg, 1 mmol) 과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol)을 무수 아세토니트릴 (5 ml) 용매하에서 50oC 조건으로 2.5시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온으로 하여 용매를 증발 농축시킨다. 그런 다음 크로마토그래피 (실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 에틸 에테르 : 노말 헥산 = 1 : 1)를 통하여 207 mg (91 %)의 2',3'-헥실리덴-D-리본닉-감마-락톤 (2',3'-hexylidene-D-ribonic-γ-lactone)을 얻었다.5 '-(4,4'-dimethoxytrityl) -2'-3'-hexylidene- D -ribonic-gamma-lactone (530 mg, 1 mmol) with tetrabutyl ammonium peroxy disulfate (1.35 g, 2 mmol) were reacted under anhydrous acetonitrile (5 ml) solvent at 50 ° C. for 2.5 hours. After the starting material is removed, the solvent is evaporated to concentration at room temperature. Then 207 mg (91%) of 2 ', 3'-hexylidene via chromatography (silica gel column; 20 cm x 3 cm, Merck 70-230, solvent; ethyl ether: normal hexane = 1: 1) - D - Nick ribbon-gamma-lactone (2 ', 3'-hexylidene- D -ribonic-γ-lactone) was obtained.

1H NMR (DMSO-d6) d 1.36-1.68 (br, 10H), 2.51 (t, 1H), 3.75-3.82 (m, 1H), 3.93-4.01 (m, 1H), 4.62 (s, 1H), 4.77 (dd, 2H). 1 H NMR (DMSO-d 6 ) d 1.36-1.68 (br, 10H), 2.51 (t, 1H), 3.75-3.82 (m, 1H), 3.93-4.01 (m, 1H), 4.62 (s, 1H) , 4.77 (dd, 2H).

(실시예 6)(Example 6)

5'-(4,4'-디메톡시트리틸-3'-t-부틸 디메틸 실릴 티미딘 (658 mg, 1 mmol)과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol)을 무수 아세토니트릴 (5 ml) 용매하에서 50oC 조건으로 1.5시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온으로 하여 용매를 증발 농축시킨다. 그런 다음 크로마토그래피 (실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 염화 메틸렌 : 메탄올 = 10 : 1)를 통하여 331 mg (93 %)의 3'-t-부틸 디메틸 실릴 티미딘을 얻었다.5 '-(4,4'-dimethoxytrityl-3'-t-butyl dimethyl silyl thymidine (658 mg, 1 mmol) and tetrabutyl ammonium peroxy disulfate (1.35 g, 2 mmol) were anhydrous acetonitrile (5 ml) under a solvent at 50 ° C. for 1.5 hours, after removal of the starting material, the solvent was evaporated to concentration at room temperature, followed by chromatography (silica gel column; 20 cm x 3 cm, Merck). 70-230, solvent; methylene chloride: methanol = 10: 1) gave 331 mg (93%) of 3'-t-butyl dimethyl silyl thymidine.

1H NMR (DMSO-d6를 한 방울 포함한CDCl3) d -0.32 (s, 6H), 0.47 (s, 9H), 1.46 (s, 3H), 1.71-1.77 (m, 2H), 2.94 (s, 1H), 3.28-3.34 (m, 2H), 3.66 (br, 1H), 4.05-4.06 (m, 1H), 5.86 (t, 1H),7.30 (s, 1H), 10.49 (s, 1H). 1 H NMR (CDCl 3 with one drop of DMSO-d 6 ) d -0.32 (s, 6H), 0.47 (s, 9H), 1.46 (s, 3H), 1.71-1.77 (m, 2H), 2.94 (s , 1H), 3.28-3.34 (m, 2H), 3.66 (br, 1H), 4.05-4.06 (m, 1H), 5.86 (t, 1H), 7.30 (s, 1H), 10.49 (s, 1H).

(실시예 7)(Example 7)

5'-트리틸 유리딘 (462 mg, 1 mmol)과 테트라부틸 암모늄 퍼옥시 디술페이트 (1.35 g, 2 mmol)을 무수 아세토니트릴 (5 ml) 용매하에서 80oC 조건으로 5시간 동안 반응시켰다. 출발 물질이 제거된 후 온도를 상온으로 하여 용매를 증발 농축시킨다. 그 후에 크로마토그래피 (실리카 겔 칼럼 ; 20 cm x 3 cm , Merck 70-230, 용매 ; 에틸 아세테이트 : 이소프로필 알코올 : 물 = 4 : 1 : 2)를 통하여 200 mg (82 %)의 유리딘을 얻었다.5'-trityl uridine (462 mg, 1 mmol) and tetrabutyl ammonium peroxy disulfate (1.35 g, 2 mmol) were reacted for 5 hours at 80 ° C. in anhydrous acetonitrile (5 ml) solvent. After the starting material is removed, the solvent is evaporated to concentration at room temperature. Subsequent chromatography (silica gel column; 20 cm x 3 cm, Merck 70-230, solvent; ethyl acetate: isopropyl alcohol: water = 4: 1: 2) yielded 200 mg (82%) of uridine. .

1H NMR (DMSO-d6) d 3.59 (q, 2H), 3.85 (m, 1H), 3.97-4.05 (m, 2H), 5.10 (br, 2H), 5.39 (br, 1H), 5.67 (d, 1H), 5.79 (d, 1H), 7.90 (d, 1H). 1 H NMR (DMSO-d 6 ) d 3.59 (q, 2H), 3.85 (m, 1H), 3.97-4.05 (m, 2H), 5.10 (br, 2H), 5.39 (br, 1H), 5.67 (d , 1H), 5.79 (d, 1H), 7.90 (d, 1H).

본 발명은 테트라부틸 암모늄 퍼옥시 디술페이트(Tetra-n-butylammonium peroxydisulfate)를 이용한 뉴클레오시드의 5'-히드록시기의 선택적 탈보호화 및 유용성에 있다. 종래에 산성 조건 에서 쉽게 파괴되던 글리코시딕 C-N결합이 영향을 받지 않고, 온화한 조건에서도 매우 좋은 수율로 탈보호화가 가능하고 또한 t-부틸 디메틸 실릴, 이소프로필리덴 케탈, 헥실리덴 케탈등의 알코올 보호기에도 영향을 주지 않는 효과가 있다.The present invention resides in the selective deprotection and utility of 5'-hydroxy groups of nucleosides with tetra-n-butylammonium peroxydisulfate. Glycosidic CN bonds, which were easily broken under acidic conditions in the past, are not affected, and deprotection is possible in very good yields even under mild conditions, and alcohols such as t-butyl dimethyl silyl, isopropylidene ketal, and hexylidene ketal There is no effect on the protector.

Claims (5)

구조식[1]로 표시되는 테트라부틸 암모늄 퍼옥시 디술페이트 (tetra-n-butyl ammo nium peroxydisulfate)와 트리틸(trityl) 유도체로 보호된 히드록시기를 갖는 뉴클레오시드나, 또는 동시에 t-부틸 디메틸 실릴(t-butyldimethylsilyl), 케탈(ketal) 등으로 보호된 히드록시기를 갖고 있는 뉴클레오시드를 반응시킨 후 중성인 무수상태에서 트리틸유도체로 보호된 히드록시기를 탈보호화 반응시키는 것을 특징으로 하는 테트라부틸 암모늄 퍼옥시 디술페이트를 이용한 히드록시기의 탈보호화 방법.Nucleosides having a hydroxy group protected with tetra-n-butyl ammonium peroxydisulfate and trityl derivatives represented by structural formula [1], or simultaneously t-butyl dimethyl silyl ( Tetrabutyl ammonium peroxy, characterized by reacting a nucleoside having a hydroxyl group protected with t-butyldimethylsilyl, ketal, etc., and then deprotecting the hydroxyl group protected with a trityl derivative in a neutral anhydrous state. Method for deprotection of hydroxy group using disulfate. [구조식 1][Formula 1] 트리틸 유도체로 보호된 히드록시기를 갖는 뉴클레오티드를 구조식[1]로 표시되는 테트라부틸 암모늄 퍼옥시 디술페이트와 반응시킨 후 히드록시기를 중성인 무수상태에서 탈보호화 반응시키는 것을 특징으로 하는 테트라부틸 암모늄 퍼옥시 디술페이트를 이용한 히드록시기의 탈보호화 방법.Tetrabutyl ammonium peroxy disulfide, characterized by reacting a nucleotide having a hydroxy group protected with a trityl derivative with tetrabutyl ammonium peroxy disulfate represented by Structural Formula [1] and then deprotecting the hydroxyl group in a neutral anhydrous state. Method for deprotection of hydroxy group using pate. 구조식[1]로 표시되는 테트라부틸 암모늄 퍼옥시 디술페이트와 트리틸 유도체로 보호된 히드록시기들을 갖고 있으며, 동시에 t-부틸 디메틸 실릴로 보호된 히드록시기를 갖고 있는 알코올과 반응시켜 중성인 무수상태에서 트리틸 유도체들로 보호된 히드록시기 만을 선택적으로 탈보호화 반응시키는 반응을 특징으로 하는 테트라부틸 암모늄 퍼옥시 디술페이트를 이용한 히드록시기의 탈보호화 방법.Tetrabutyl ammonium peroxy disulfate and trityl derivatives represented by Structural Formula [1], which have hydroxy groups protected at the same time with tri-butyl dimethyl silyl-protected hydroxy groups and react with an alcohol having a trityl in neutral anhydrous state A method for deprotecting a hydroxy group using tetrabutyl ammonium peroxy disulfate, characterized in that the reaction of selectively deprotecting only the hydroxy group protected by derivatives. 제3항에 있어서,The method of claim 3, t-부틸 디메틸 실릴 대신에 케탈(ketal)로 보호된 히드록시기를 갖고 있는 알코올과 반응시켜 중성인 무수상태에서 트리틸 유도체들로 보호된 히드록시기를 탈보호화 반응시키는 반응을 특징으로 하는 테트라부틸 암모늄 퍼옥시 디술페이트를 이용한 히드록시기의 탈보호화 방법.Tetrabutyl ammonium peroxy, characterized in that it reacts with an alcohol having a ketal-protected hydroxy group instead of t-butyl dimethyl silyl to deprotect the hydroxy group protected with trityl derivatives in a neutral anhydrous state. Method for deprotection of hydroxy group using disulfate. 제1항 내지 제4항에서 선택된 어느항에 있어서,The method according to any one of claims 1 to 4, 트리틸 유도체는 트리틸,모노 메톡시 트리틸,디메톡시 트리틸인 것을 특징으로 하는 테트라부틸 암모늄 퍼옥시 디술페이트를 이용한 히드록시기의 탈보호화 방법.The trityl derivative is trityl, monomethoxy trityl, dimethoxy trityl, characterized in that the deprotection of hydroxy groups using tetrabutyl ammonium peroxy disulfate.
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